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Dr. Ian Flinn, Medical Oncologist specializing in hematologic malignancies at Tennessee Oncology, discusses the recent FDA approval of duvelisib for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT (Intro Music Playing) As a background to today's discussion, the PI3K are a family of lipid kinases that sit at the crossroads of numerous signaling events that drive many malignancies, including certain lymphomas, and chronic lymphocytic leukemia. There are four isoforms of the PI3K-- alpha, beta, delta, and gamma. Isoform specific inhibitors are attractive because they may lead to efficacy without the toxicity of pan inhibitors. Idelalisib, which is a delta isoform inhibitor, was the first PI3K inhibitor be approved for lymphoma in CLL. The delta isoform is a particular interest in B cell malignancies because its expression is normally restricted to cells of a hematopoietic origin. In data from gene knockout models, show that it has a key role in B cell signaling, development, and survival. Selective targeting of the delta isoform should not alter insulin signaling, which is mediated by the ubiquitously expressed alpha isoform. However, narrow targeting could lead to mechanisms of resistance to upregulation of other isoforms. This has been demonstrated in mantle cell lymphoma where the alpha isoform is expressed in relapse patients. Duvelisib is a dual inhibitor of both the delta and gamma isoforms of the PI3K. Inhibiting the gamma isoform may be important because of its inhibitory effect, not only in the malignant cell, but also in the micro-environment, which provides important survival signals to malignant cells. Both idelalisib and copanlisib, an inhibitor of the delta and alpha isoforms, are currently FDA approved for third line follicular cell lymphoma. And idelalisib is approved in combination with rituximab in relapse CLL. On September 24, 2018, the Food and Drug Administration granted approval for duvelisib for patients with relapsed refractory chronic lyphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma after at least two prior therapies. The approval of duvelisib in CLL was based on the DUO trial, a large international randomized phase III trial comparing duvelisib, at 25 milligrams orally, twice daily, to ofatumumab, given according to the package label. The results of the duo trial have been published in Blood. In a subset analysis of 196 patients receiving at least two prior therapies, the median progression pre-survival was 16.4 months in the duvelisib arm, and 9.1 months in the ofatumumab arm, with a hazard ratio of 0.40. The overall response rate of 78% with duvelisib was twice the 39% seen with ofatumumab. The follicular lymphoma indication is based on the Dynamo trial, a single arm multi-center trial of duvelisib, which enrolled 83 patients with follicular lymphoma who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The overall response rate, determined by an independent response committee, was 42%. Of the 35 responding patients, 15, or 43%, maintained responses for at least six months. And 6, or 17%, maintained responses for at least 12 months. The most common adverse reactions with an instance of greater than or equal to 20% were diarrhea, or colitis, neutropenium, rash, fatigue, pyrexia, cough, nausea, upper respiratory tract infection, pneumonia, muscle skeletal pain, and anemia. Over the last decade, we've seen substantial advances in the treatment of low grade lymphoma and CLL, especially in the front-line setting. Unfortunately for patients with relapse and refractory disease, new agents are needed. The approval of duvelisib is an important addition to our armamentarium for these patients. And we'll have an immediate impact. However, to have its greatest effect, strategies will need to be devised to move this drug earlier in the natural history of these diseases. Such approaches might include alternative dosing and scheduling, as well as combination regiments. Duvelisib is a novel PI3K inhibitor and is differentiated from other PI3K inhibitors, because it targets both the delta and gamma isoforms. Consequently, it is being studied in a broader array of diseases, including T cell malignancies, where promising activity has been seen. (Outro Music Playing) Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on drug approvals visit the comprehensive e-learning center at university.asco.org.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast Series. Is my name Shannon McKernin and today, I'm interviewing Dr. Elena Stoffel from the University of Michigan, lead author of "Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion.” Thank you for being here today, Dr. Stoffel. I'm delighted to join you. So first, can you tell us what a professional clinical opinion is and why this topic is so important to ASCO? Well, a provisional clinical opinion is a statement that ASCO puts out when we are seeing trends that are relevant to the care of our patients but that may not necessarily have the level of evidence needed to include in a true clinical guideline. This particular provisional clinical opinion that deals with the management of patients with pancreatic cancer and their families is based on some new data that has been published regarding the prevalence of inherited factors influencing pancreatic cancer risk. So what are the key statements of this Provisional Clinical Opinion or also known as a PCO? This particular provisional clinical opinion, which is about just the inherited susceptibility to pancreatic cancer, was prompted by several recent publications, which found that the prevalence of genetic predisposition among patients with pancreatic cancer was much higher than we had originally anticipated. And this is relevant because in talking about pancreatic cancer as one of the deadliest cancers in both in the United States and worldwide, we are very interested in finding ways to reduce the morbidity from this cancer to patients and their families. And this particular provisional clinical opinion addresses the role that genetic risk assessment should have in the care of pancreatic cancer patients and also the role for clinical genetic testing, as well as the risks and benefits of pancreatic cancer screening for at risk family members. What considerations are there for having these conversations with patients and their families? Well, many times when we see families affected with cancer, one of the questions they have is what is the likelihood that this will happen to other individuals in our family and what can we do to prevent cancers in other family members. And I think what's important here is that review of the data from multi-gene panel genetic testing in unselected individuals diagnosed with pancreatic cancer identified pathogenic germline variants in 1 out of every 10 individuals. And this is really important because when you think about it, if 1 out of every 10 patients with pancreatic cancer develop their cancer in the setting of a genetic predisposition syndrome, this has tremendous implications for management both for them as well as for their family members. One of the most common inherited cancer syndromes identified in families affected with pancreatic cancer is hereditary breast ovarian cancer associated with mutations of BRCA1 and BRCA2. As you know, there are definite screening recommendations we make for individuals who carry these genetic alterations. And certainly if a family member is diagnosed with a genetic alteration, then that has an impact for cancer screening and management. Furthermore, there are emerging data about the utility of pancreatic cancer screening in high risk individuals. And while there's still some controversy about how to screen individuals at risk for pancreatic cancer, certainly there are some emerging data suggesting that this may have a role for early detection. And finally, the panel included a discussion section on the limitations of the research and future directions. So what are the key points of this section? I think that what we're learning is with genetic testing, and particularly with multi-gene panel testing, we are we often find unexpected results. Certainly variants of uncertain significance are not uncommon when multi-gene panel tests are used. And being able to interpret the clinical significance of some of these genetic test results can pose some challenges, especially for clinicians who don't have specific expertise in genetics. Certainly being able to deal with the volumes of patients who need genetic testing who are also battling pancreatic cancer, we want to make sure that we have the resources to be able to offer genetic testing to everyone who needs it. And finally, in talking about screening for pancreas cancer, while there are some studies that have demonstrated that screening with MRIs and/or endoscopic ultrasounds has led to early detection and down staging of cancers in some cases, larger studies are needed to be able to refine more specifically who and how to screen individuals at risk for pancreas cancer. Great. Thank you so much for taking your time today to discuss this PCO with us, Dr. Stoffel. Thank you very much for having me. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. If you've enjoyed what you heard today, please rate and review the podcast and refer the show to a colleague.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Scott Morgan from the Ottawa Hospital and University of Ottawa, lead author on "Hypofractionated Radiation Therapy for Localized Prostate Cancer: an ASTRO, ASCO, and AUA Evidence-Based Guideline.” Thank you so much for being here today, Dr. Morgan. It's my pleasure, Shannon. I'm happy to take part in the podcast and hopefully share the highlights of the guideline with your listeners. So first, can you give us a general overview of what this guideline covers? Yeah. So the guideline covers really hypofractionated external beam radiation therapy, which is a treatment for localized prostate cancer, and for the non-radiation oncology folks in your audience, I think it's important to begin by placing the guideline sort of in its context and going over some of the terminology that we use as radiation oncologists. So external beam radiotherapy, it's a standard treatment-- standard local treatment option for men with localized prostate cancer. It gives outcomes which are really equivalent to those of radical prostatectomy or brachytherapy, which are the other two standard local treatment options. And traditionally, it's given in small daily fractions over several weeks and the usual daily fraction size is 1.8 to 2 Gray per day. And this is called conventional fractionation. And that really translates into a course of about seven and a half to nine weeks of treatment. And so that total dose which is delivered in those daily treatments, five days a week, is about 76 to 80 Gray. And that's what we call conventional or standard fractionation. And there's a theoretical framework in radiation medicine and there's some evidence to accompany that that suggests that prostate cancer is quite sensitive to radiation fraction size. And just to give a brief primer, for any tissue, cancerous or non-cancerous, there's a sensitivity to fraction size and it's characterized by something called the alpha-beta ratio. And for prostate cancer, that's felt to be low compared to most other cancers, the alpha-beta ratio, and indeed, it's thought to be lower than the adjacent dose-limiting normal structure, which is the rectum. And so an implication of that is that hypofractionation, and by that we mean daily fraction size of more than 2 Gray, might improve the therapeutic ratio of radiation therapy in localized prostate cancer. Now the guideline-- and I think it's important to emphasize this-- it draws a distinction between what we call moderate hypofractionation and ultra-hypofractionation. Clearly, fraction size is a continuous variable, so any subdivision that we might make is necessarily a bit arbitrary, but it turns out that at least in clinical practice, there's been really two distinct approaches to hypofractionation that have arisen. And one of these is moderate hypofractionation and that's an approach where the fraction size is modestly higher than 2 Gray per fraction, and in the guideline, it's been defined as a fraction size between 2.4 and 3.4 Gray, whereas ultra-hypofractionation, this is defined in the guideline as a fraction size greater than 5 Gray. And it's also been referred to in the literature as extreme hypofractionation or Stereotactic Body Radiation Therapy, SBRT, or SABR, Stereotactic Ablative Radiation Therapy. But in any case, we are talking here about, with ultra-hypofractionation, with radical courses of treatment that are often delivered over as few as five fractions, often on an alternate day approach over two or two and a half weeks. And so the guideline really was largely motivated by the publication of a number of randomized trials, including four large-scale trials in the past two years that have compared conventionally fractioned radiation therapy and moderately hypofractionated radiation therapy. So that is really what stimulated the guideline, which was the evidence concerning moderately hypofractionated radiation therapy. But at the same time, there has been an increasing use in routine clinical practice that's been observed of ultra-hypofractionated radiotherapy, so the decision was made to make recommendations on it as well. So ASTRO, American Society for Radiation Oncology, in collaboration with ASCO and the AUA, convened a panel of radiation oncologists, medical physicists, urologists, radiation oncology resident, patient representative, and a systematic review of the literature was conducted and their recommendations have been made on the basis of this systematic review. So the aim was to provide recommendations on use of both moderate hypofractionation and ultra-hypofractionation, in particular with reference to oncologic outcomes, toxicity, and quality of life. So we didn't directly consider health economic endpoints, though clearly the very nature of hypofractionation is such that there are potential advantages in terms of cost and convenience for patients. And what are the key recommendations of this guideline? We separated the key recommendations into three main groups and the first set of recommendations pertains to moderate hypofractionation, and these are generally based on the highest-quality evidence. So they could be viewed as the strongest recommendations in the guideline. And the second set of recommendations concern ultra-hypofractionation. They're somewhat less strong given they're based on somewhat weaker evidence. And then the third set of recommendations relate to some of the technical aspects of the planning and delivery of hypofractionated radiation therapy. So, dealing with the moderate hypofractionation recommendations first, arguably the most important recommendation of the guideline is that the panel has recommended that in patients with localized prostate cancer who are candidates for external beam radiation therapy, moderate hypofractionation should be offered. And this is graded as a strong recommendation. It's based on high-quality evidence and it applies to patients across all risk groups. So it applies to patients with low-risk prostate cancer who require active treatment or who have declined active surveillance and it also applies to patients with intermediate-risk or high-risk localized prostate cancer. And why really does it apply to all these groups? It's essentially because these groups are well-represented in the trials of moderate hypofractionation. And the trials have shown that moderate hypofractionation really gives similar outcomes in terms of efficacy to conventional fractionation. Now one caveat I guess that I should say is that the trials generally only looked at radiation therapy to the prostate rather than radiation therapy to the prostate as well as the pelvic lymph nodes. So the panel's recommendations regarding moderate hypofractionation don't apply to the scenario where the clinician has decided to include the pelvic lymph nodes in the radiation therapy volume. The panel also made recommendations with respect to toxicity and quality of life, and specifically, they did recommend that men should be counseled about a small increased risk of acute gastrointestinal toxicity, typically rectal toxicity, with moderately hypofractionated radiation therapy. And they should also be counseled that moderately hypofractionated radiation therapy has a similar risk of late GI toxicity and also has a similar risk of both acute and late GU toxicity compared to conventional fractionation. The only difference was seen in acute GI toxicity. And I think it's probably worth dwelling on this a little bit more. Probably the most granular data on acute GI toxicity comes from the CHHiP trial. This was a trial from the UK. It was far and away the largest randomized trial of moderate hypofractionation versus conventional fractionation. And they followed the amplitude of GI toxicity very carefully over the short and long term and what they did found was that in the early weeks, there was greater peak acute GI toxicity with moderate hypofractionation, but this difference had really disappeared by about 18 weeks after the start of radiotherapy. So within a few months, there was no difference, and afterwards, there was no consistent difference in long-term GU or GI toxicity across these trials. Now I guess I should mention that, at the current time, that the median follow-up of most of these trials is between five and six years, so arguably, the last word hasn't been written. The panel also offered conditional recommendations on particular moderate hypofractionation regimens. There were multiple different regimens that were evaluated but most were not compared head-to-head. And the panel preferred two particular regimens-- 60 Gray and 20 fractions over four weeks or 70 Gray and 28 fractions over five and a half weeks, as these were the two regimens that were evaluated in the largest populations. And of these two, likely the strongest evidence supports 60 Gray and 20 fractions, given it was used in two different trials and it was used across all risk groups and with or without concomitant hormonal therapy. So those were the recommendations regarding moderate hypofractionation. So moving to ultra-hypofractionation, again, this is talking about fraction size of at least 5 Gray, typically a course of as few as five fractions over perhaps two or two and a half weeks. I think it's important to say that, at the time we were preparing this guideline, there were no published efficacy or toxicity data from randomized trials comparing ultra-hypofractionation and conventional fractionation. So the strengths of the recommendations made by the panel is correspondingly lower than was the case for moderate hypofractionation. But having said that, there are several prospective non-randomized studies that have been published and have documented safe delivery of ultra-hypofractionation for appropriately-selected patients and pretty good biochemical control and low toxicities have been observed in these studies. But again, relatively few have follow-up beyond five years. So what the panel recommended was that in men with low-risk prostate cancer-- and the bulk of the data to date for ultra-hypofractionation has been in this group-- panel conditionally recommended that in those who decline active surveillance and choose active treatment with radiation therapy, that ultra-hypofractionation may be offered as an alternative to conventional fractionation. Again, this is a conditional recommendation. In men with intermediate-risk prostate cancer, the panel has conditionally recommended that ultra-hypofractionation may be offered as an alternative to conventional fractionation but it's strongly recommended in this group that these patients be treated as a part of a clinical trial-- and there are several clinical trials ongoing-- or as part of the multi-institutional registry. And then finally, in patients with high-risk localized prostate cancer, there was really insufficient comparative evidence for the panel to suggest offering this outside of a clinical trial or outside of a registry. Regarding particular regimens, that the panel again made a conditional recommendation that a schedule of 35 Gray to 36.25 Gray and five fractions delivered to the planning target volume could be offered and that it recommended against consecutive daily treatments for this schedule. So I think it's again important to note that compared to moderate hypofractionation, the ultra-hypofractionation literature is really substantially less mature and it is evolving rapidly. And therefore, a short-term update of this guideline to address new data pertaining specifically to ultra-hypofractionation is likely going to be necessary. And then I mentioned there was a third set of recommendations and these pertain to the technical aspects of planning and delivering radiation therapy. And these probably are not of core interest to your audience, but briefly, the guideline recommends that in the planning of hypofractionated radiotherapy, that normal tissue constraints and target volumes derive from published reference standards the use and that image guidance and intensity modulation at one form or another are recommended in delivering hypofractionated radiotherapy. Great. Thank you for the overview of those guideline recommendations. So why is this guideline so important and how will it change practice? Yeah. I guess the first point to make is that the guideline potentially can inform the care of a very large number of patients. Across North America, about 200,000 patients a year are diagnosed with prostate cancer and its far and away that the most prevalent non-dermatologic cancer in men and it's the third-leading cause of cancer death in men, at least in North America. So the vast majority of those 200,000 men are diagnosed with localized disease at the time of presentation and therefore they're potentially treatable with radiation therapy and therefore the guideline is relevant to these patients. Prior to the publication of the trials that motivated this guideline, the overwhelming majority of these men who chose external beam radiotherapy as their primary treatment have been treated with conventionally fractionated therapy. In other words, seven and a half to nine weeks of treatment. And already, since the publication of these trials-- the trials of moderate hypofractionation-- we're talking really about moderate hypofractionation because I think that is where the guideline will have its impact, at least in the short term. In the jurisdiction where I practice in Canada, practice has already substantially changed in light of these trials, and I think a large majority of patients with localized prostate cancer choosing external beam radiation therapy are now typically being treated with a moderately hypofractionated approach, typically a four-week schedule. So it will be interesting to see if a similar change is occurring or will occur over time in the United States, particularly informed or potentially informed in part by this guideline. And then finally, with respect to ultra-hypofractionation, I think again I have to note that this is a very dynamic space in terms of evidence and there are a number of large-scale trials looking at ultra-hypofractionation and comparing it to either conventional fractionation or moderate hypofractionation that are in progress or near to reporting. And so again, an update of the guideline in the short-term as data emerges from these studies will likely be important and it may ultimately influence practice as well on a large scale. And finally, how will these guideline recommendations affect patients? So I think in the short term, that the recommendation that has the potential to impact patients in the greatest way is the recommendation regarding moderate hypofractionation. And the guideline really recommends that this is a management approach that substantially reduces the treatment burden without compromising treatment efficacy and without increasing the risk of long-term side effects. So in my view, the move to moderately hypofractionated radiation therapy is a win for patients with localized prostate cancer who choose radiation therapy as their primary treatment modality. And so moderate hypofractionation really represents about a halving of the overall treatment time in some patients. And those who live, for example, in rural or remote areas and who need to travel considerable distance to have their treatment, a halving of treatment time is significant. But I think even more generally, halving of treatment time is significant for patients regardless of where they live. And clearly there are also benefits potentially in terms of cost and also benefits in terms of for the health care system but those really weren't specifically studied in the guideline. Great. Thank you so much for your time today, Dr. Morgan, and thank you for your work on this important guideline. My pleasure, Shannon, and thank you for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Dr. Axel Hauschild, professor of dermatology and head of the dermato-oncology department at the University Hospital of Kiel in Germany, discusses the recent FDA approval of cemiplimab, a PD-1 antibody treatment for patients with metastatic or locally advanced cutaneous squamous cell carcinomas. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Axel Hauschild. I'm a professor of dermatology and head of dermato-oncology at the University Hospital of Kiel in Germany. Today, we will discuss the approval of cemiplimab, a new PD-1 antibody for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas. As a background to today's discussion, immune checkpoint inhibitors are active therapies in patients with other cutaneous malignancies, like melanomas and mucosal carcinomas already. So far, chemotherapy was given as a routine for patients with advanced or metastatic cutaneous malignancies, and occasionally, cetuximab, an EGFR inhibitor. However, in almost all of these patients, the responses were short-lasting. The analysis of the tumor mutational burden indicated a high sensitivity of more or less all UV-induced cutaneous malignancy for immune checkpoint inhibitors. Therefore, theoretically, cutaneous squamous cell carcinomas are ideal tumors for the treatment with PD-1 or PD-ligand 1 antibodies. On September 28 of 2018, cemiplimab was approved by the FDA for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas who are not candidate for curative surgery or curative radiation. These data led to the approval of a flat dose of 350 milligrams cemiplimab infused over 30 minutes every three weeks. The approval of cemiplimab was based on a high number of clinically meaningful and durable objective responses observed in patients with two different clinical trials. The results have already been published in 2018, in June, in the New England Journal of Medicine. Both clinical trials were non-randomized, multicenter studies in patients for whom surgery or irradiation was not recommended. Among 108 patients with advanced cutaneous squamous cell carcinomas, including 75 metastatic patients, the overall response rate was 47%, with 4% complete and 44% partial responses. There were no significant differences in the response rate between patients with metastatic and those with locally advanced disease. The median response duration was not reached. And 61% of the responses were durable for six months or longer. Response rates and durability results were consistent across the advanced squamous cell carcinoma subtypes. For patients with locally advanced cutaneous squamous cell carcinomas, the radiographic response rate correlated with clinically relevant shrinkage of visible and often disfiguring tumors demonstrated in the photographic data obtained in these clinical trials. Safety data were evaluable from 434 patients who received cemiplimab in both clinical trials. Serious adverse events were typically immune-mediated, such as colitis or pulmonitis. And in some patients, infusion reactions were observed. The most common adverse events were fatigue, rash, and diarrhea. The treatment discontinuation rate was 12%. The approval of cemiplimab marks a significant advancement in the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas. Cemiplimab is considered as a new standard of care in these patients, since not only an impressive response rate of almost 50%, but also durable responses were observed. As mentioned before, previously, chemotherapies and cetuximab have been used for these patients with limited efficacy, particularly because most responses were only short-lasting. Important to mention is that the approval is not going along with a biomarker test, such as the measurement of PD-ligand 1 expression. Therefore, cemiplimab can be used for all comers with metastatic or locally advanced cutaneous squamous cell carcinomas. So far, there are no data available when cemiplimab has been combined with other agents or irradiation. Also, data from the adjuvant of PD-1 antibodies in high-risk cutaneous squamous cell carcinoma patients are outstanding. However, clinical trials on cemiplimab and other PD-1 antibodies are already planned. In conclusion, cemiplimab adds significantly to the success story of PD-1 and PD-ligand 1 antibodies in cutaneous malignancies. The approval of cemiplimab for cutaneous squamous cell carcinomas leads to changes in the current guidelines for this tumor. Thank you very much for listening to this week's episode of the ASCO University Weekly Podcast. For more information on immune therapy and the treatment of cutaneous squamous cell carcinomas, visit the comprehensive eLearning Center at university.asco.org. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a moment to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin and today I'm interviewing Dr. Valerie de Haas from Princess Máxima Center for Pediatric Oncology in the Netherlands, lead author on "Initial Diagnostic Workup of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the CAP and ASH Guideline.” Thank you for being here today, Dr. de Haas. Thank you. So first, can you give us a general overview of what this guideline covers? Well, yes. The laboratory evaluation of patients who are suspected of having acute leukemia is very complex, and it has evolved significantly with the incorporation of advanced laboratory techniques. The traditional backbone of initial workup of AL, of acute leukemia, is composed of ctyomorphology, cytochemistry, immunophenotyping, and molecular cytogenetics. These techniques are the backbone of the initial diagnostic workup of acute leukemia. This is leading to risk stratification and fine tuning of the therapy by molecular signatures. The advanced molecular diagnostics, such as next-generation sequencing, has become more important in the diagnosis and in the risk stratification of acute leukemia. This guideline is meant for both pediatric and adult patients, and it was initially published in 2017. This year, we reviewed this guideline, and we have taken into account two important developments. First, since 2017, we've seen that there are major advances in molecular techniques and also that we can identify and validate new molecular markers. And those two events have contribute to a better risk stratification. And the second development is the effect that the WHO classification was revised in 2017 which also has led to new risk recoveries and refined subclassifications. So what are the key recommendations of this guideline? Well, in total, we have reviewed 27 guideline statements by the ASCO endorsement expert panelists. And discussion points are used to summarize issues that were identified from the updated literature. The ASCO expert panel determined that the recommendations from the guideline as published in 2016 are clear, thorough, and they are based upon the most relevant scientific evidences. We fully endorse the CAP-ASH guideline on initial diagnostic workup of acute leukemia. And we decided to include some discussion points according to clinical practice and according to the updated literature. In fact, we identified four categories of key recommendations. The first one is the initial diagnostics focusing on basic diagnostics and determination of risk parameters. This concerns, in total, about 11 guideline recommendations, and they give an overview of the initial workup varying from the collection of the clinical history of the patient to initial basic diagnostics by cytomorphology, flow cytometry and molecular cytogenetic analysis of peripheral blood, bone marrow, and cerebrospinal fluids. Secondly, the second category were molecular markers and MRD detection, and they were addressed by 10 of the recommendations. And these recommendations give a structural overview of the molecular and cytogenetic workup for acute lymphoblastic leukemia versus acute myeloid leukemia identifying different prognostic markers. Also, the detection of MRD is taken into account in this recommendation. There is a major difference between children and adults, and this part is given most attention in the discussion part as the developments have been major during the past few years. The third one is the context of referral to another institution with expertise in the management of acute leukemia. This is addressed by four recommendations, emphasizing the point that referral to an institution with specific expertise is of major importance for the central workup of acute leukemia. And finally, the final reporting and report keeping is reflected in three recommendations, mainly supporting conclusions from 2017 which were describing the fact that the complete report with basic diagnostics in one central report should be available within 48 to 72 hours. And this should be followed by complete, final, comprehensive report in one or two weeks. So can you tell us about those discussion points that were made and why the panel decided to include these? The discussion points include mostly issues regarding diagnostics that involve flow cytometry and molecular techniques as addressed in part one and two of the guidelines. We think that the cytomorphologic assessment is essential for initial diagnosis of acute leukemia. Multicolor flow cytometry using 8 to 10 colors has led to a better distinction between myeloids, lymphoid, and mixed lineage blast origin. Even when the number of cells are limited, for instance in CNS involvement, fine needle aspirate of extramedullary leukemic infiltration, or skin biopsy for leukemic cutis. Also, it was suggested to better assess the central nervous system involved in leukemia. The expert panel recommends the immunophenotyping studies as an additional detection technique next to the cytomorphological examination of cytospins and particularly for those with a low level involvement of acute leukemia that cannot be well addressed by a morphologic examination only. The TDT immunohistochemistry staining of cytospins has alternatively been used for detection of CNS disease in AML and evaluation of CSF by multicolor flow cytometry has been recently adopted in some centers. Flow cytometry, using at least six, but we now use in some laboratories, even 8 to 10 colors has led to a much more specific in tentative diagnosis. And this has improved the detection of CNS involvement. The use of molecular tools, for instance, polymerase change reaction, PCR, NGS for low-level CSF involvement is still under study, and therefore, we did not recommend this in our discussion. Regarding the molecular markers and MRD detection, the discussion here was mainly based upon the results of translational research supported by better molecular detection techniques. And those molecular diagnoses have been developing in the past few years with the inclusion of many more molecular markers. And they included one of the key diagnostic criteria in the revised WHO classification, which was revised in 2017. And we made substantial changes that have been made in the ASH-CAP guidelines concerning molecular diagnostics. Those newly identified targets by advanced molecular techniques give possibilities for better risk stratification. Some examples of better molecular characterization of acute lymphoblastic leukemia are, for instance, additional testing for MLL translocations. Furthermore, we can look in patients with T-ALL for NOTCH1, and FBXW7 mutations. The Ikaros family zinc finger gene, the IKZF1 gene is frequently deleted in adults as well in children with B-ALL. And it was shown to have an independent prognostic significance and was also associated with poor clinical outcome. In the current text of the current risk that the protocols IKZF1 should be regularly included in the screening panels for all ALL patients. If we look for examples for better characterization of AML, acute myeloid leukemia, we have found an increasing number of additional cytogenetic aberrations, like for instance FLT3 ITD which is associated with poor outcome. Another example is appropriate mutational analysis for kids, which can be detected both in adult patient as pediatric patients with a confirmed core binding factor acute myeloid leukemia. So this is myeloid leukemia with a translocation A21, RUNX1, or inversion 16. This recommendation is very strong in adults, whereas in children, this prognostic fact impact remains unclear. So there have been proven several publications which refer to a similar prognosis for children and others who refer to a poor prognosis in comparison to known mutated genes. So we suggest to test for this mutation in adults, especially, but also in children to learn from it. Finally, emerging evidence supports molecular studies as principle test for monitoring minimal residual disease of acute leukemia. And there are several key molecular markers that are included in the initial workup, which will be carried on for monitoring MRD, for instance, PML- RAR-alpha, RUNX1-RUNXT1, CBFB-MYH11, and NPM1, CEBP-alpha and others. Beside those aforementioned markers, it's very important to screen for other molecular markers that have predictive or prognostic value in the individual. And it is possible to use them for MRD. We have found a recent consensus from the European Leukemia Net MRD Working Group, who was proposing that for detection of molecular MRD, and they refer the RT PCR platform to NGS and digital PCR platforms. Although all those molecular techniques have been developed very quickly and it is very tempting to use them for initial diagnostics, currently, not all laboratories will have all those techniques available. So the expert panel strongly advises understanding to make distinction between diagnostic that are needed in the first phase to start treatment and subsequently, treatment stratification, in contrast to the usual dose findings in a broader research. For instance, available karyotyping, FISH, PCR techniques, if possible, NGS can be used in the initial start of treatment, whereas techniques like whole exome sequencing, whole genome sequencing, RNA sequencing, and epigenomic studies are meant for a broader research. And finally, how will these guideline recommendations affect patients? Well, in the end, the patients will receive better and especially, more personalized treatment. If we have results available within two weeks from diagnosis, it will be possible to better identify which basis will better benefit from more intensified and more personalized treatment, whereas others may need less intensive treatment with less toxicity. If you use traditional techniques to do this supported by molecular techniques like karyotyping, FISH, and PCR techniques, and in the end, following MRD to see which patients are responding to treatment, MRD detection will help to identify these patients and stratify them finally to the best treatment. Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. de Haas. OK. Thanks a lot. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. If you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

In this week's episode, Dr. Danielle Shafer, Medical Director of the Clinical Trials Office at Massey Cancer Center at Virginia Commonwealth University, explores the recent FDA approval of ivosidenib for the treatment of relapsed or refractory acute myeloid leukemia. Dr. Shafer's primary clinical focus is leukemia & lymphoma in adult patients. Her research focus is limited to the same population, with a particular interest in relapsed/refractory AML. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Danielle Shafer, and I'm an assistant professor at the Massey Cancer Center at Virginia Commonwealth University. My area of specialty is leukemia and lymphoma. Today, we will discuss the approval of ivosidenib in patients with relapsed and refractory AML with a susceptible IDH1 mutation. As a background to today's discussion, somatic mutations of IDH have been identified in multiple tumor types, including AML and MDS. As a result of the mutation, there is impaired hematopoietic differentiation, as well as epigenetic alteration. IDH mutations occur in approximately 20% of adults with AML, and 5% of adults with MDS. IDH1 mutations occur in approximately 6% to 9% of adult AML patients. Enasidenib was approved by the FDA in 2017 for adult patients with relapsed and refractory AML with an IDH2 mutation. On July 20, of 2018, ivosidenib was approved by the FDA for the treatment of adult patients with relapsed and refractory AML with a susceptible IDH1 mutation, as detected by an FDA approved test. The approval of ivosidenib in the relapse to refractory setting was based on the results of a phase I dose escalation and dose expansion study published in the New England Journal of Medicine. The primary objectives of the study were to assess the safety, maximum tolerated dose, and recommended phase II dose. Of the 258 patients receiving study drug, 179 patients had relapsed and refractory disease. The median age was 67, with a range of 18 to 87 years. Patients had a median of two prior therapies, 24% had relapsed after transplant, and 59% were refractory to induction or re-induction. 59% had favorable cytogenetics. The most common co-occurring mutation was NPM1 in 26% of patients. A maximum tolerated dose was not defined, and ivosidenib 500 milligrams was selected for dose expansion. The most common adverse reactions were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, Q/T prolongation, rash, pyrexia, cough, and constipation. In the overall population, 30 day all-cause mortality was 7%. The majority of deaths were related to disease progression or complications of underlying AML. No treatment-related adverse events leading to death were seen in patients with a starting dose of 500 milligrams. IDH differentiation syndrome is of special interest, as early identification is necessary. It is similar to what has been described with ATRA and arsenic trioxide. In this study, IDH differentiation syndrome was reported in 19 patients, and was of grade 3 or higher in nine patients. Leukocytosis grade 2 or 3 accompanied differentiation syndrome in 7 of the 19 patients. Median time to onset was 29 days, with a range of 5 to 59 days. Treatment included glucocorticoids, diuretics, and hydroxyurea, if leukocytosis was present. With intervention, 17 of the 19 patients had resolution. The two remaining patients had differentiation syndrome at data cutoff. In the relapsed refractory population, the rate of complete remission or complete remission with partial hematologic recovery was 30.4%. The median duration of complete remission, or complete remission with partial hematologic recovery, was 8.2 months. The median time to response was 2.7 months. With a median follow-up of 14.8 months, the median overall survival was 8.8 months. ivosidenib is the first IDH1 inhibitor to enter the clinic for relapsed refractory AML, and clearly represents a step forward for this population. The drug is, overall, well-tolerated. Differentiation syndrome represents a unique toxicity, as early recognition is critical. Practicing physicians may encounter difficulties differentiating disease progression from differentiation syndrome in some patients. Given the success of the drug in the relapsed refractory setting, it is now being combined with other therapies and moving earlier in the treatment course. Based on the encouraging results of a phase I study, ivosidenib is currently being combined with intensive chemotherapy in a phase III study, for newly-diagnosed AML patients with IDH1 mutations. Although the drug is termed a success, the majority of patients are still dying of their disease. While some patients were bridged to transplant in the New England study, the benefit is not yet entirely clear. Additional questions emerge regarding co-mutations and IDH1 mutation clearance. Not surprisingly, in this study, there was some preliminary data to suggest that patients with IDH1 clearance had longer durations of remission and survival. We anticipate better understanding as more patients are treated with the drug. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the treatment of AML, visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING]

Dr. Shaheenah Dawood is the Head of Medical Oncology and the Head of the Breast Cancer Program at Dubai Hospital in the United Arab Emirates. Dr. Dawood completed her M.B.B.Ch at Dubai Medical College in 1998 and a Master of Public Health degree at the Harvard School of Public Health, Boston, USA in 2008. Her postgraduate medical training programs include a Fellowship at McGill University in Canada in 2006, and the Susan Komen Breast Cancer Fellowship at the University of Texas M.D. Anderson Cancer Center in 2007. Dr. Dawood is a member of various professional organizations, including the American Society of Clinical Oncology (ASCO), the American Association of Cancer Research (AACR), the Canadian Association of Medical Oncologists, the Emirates Medical Association, and the Inflammatory Breast Cancer Research Group. She is also the co-director of the Middle East Research Network. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the self-evaluation episode of the ASCO University Weekly Podcast. My name is Shaheena Dawood, and I am a consulting medical oncologist and lead of the Oncology Research program at the Comprehensive Cancer Center at the Mediclinic City Hospital in Dubai, United Arab Emirates. Today, we feature a self-evaluation question looking at the predictive and prognostic role of pathological complete response attained in the treatment of breast cancer. Let us begin by reading the question stem. Here, we have a 55-year-old woman who presents with a 4 centimeter right breast mass and palpable right axillary lymph nodes. A needle biopsy of the breast mass and a lymph node are both positive for infiltrating ductal carcinoma negative for hormone receptors and negative for HER2/neu expression. The patient is interested in breast-conserving therapy, and she is referred to you for consideration of neoadjuvant chemotherapy. Which of the following do you tell her? Your choices are, A-- patients having a complete response to neoadjuvant chemotherapy have lower local and regional recurrence rates, B-- mastectomy will be required regardless of clinical response to chemotherapy, C-- chemotherapy will be administered before and after surgery, or D-- randomized trials have shown that radiotherapy is not necessary following surgery and chemotherapy if she has a complete response. At this point, please feel free to pause the recording before we discuss the correct answer. [MUSIC PLAYING] The correct answer to this question is A. Pathological complete response in the breast and lymph nodes is associated with lower local and regional recurrence rates. A combined analysis of the NSABP B18 and B27, two large trials that evaluated the role of neoadjuvant chemotherapy, revealed that the rate of local regional recurrence decreased amongst patients who initially presented with positive lymph nodes prior to neoadjuvant chemotherapy, and who become pathologically node negative after neoadjuvant chemotherapy, especially if they also achieved a pathological complete response in the breast. Briefly, the other choices presented in this question do not represent the most appropriate answer for the following reasons. The decision regarding type of surgery in the form of mastectomy versus breast-conserving surgery is dependent on multiple factors. One of the early established benefits of neoadjuvant therapy is that it increases the probability of breast-conserving surgery, making more women candidates for lumpectomy and breast radiotherapy, who otherwise would have been treated with mastectomy. Studies have shown that chemotherapy before surgery in the neoadjuvant setting versus chemotherapy after surgery in the adjuvant setting is associated with similar outcomes. And finally, attaining a pathological complete response currently does not preclude the need for adjuvant radiation therapy, the decision of which would be made on clinical stage of disease at presentation. The NSABP51 RTOG phase III trial is ongoing to evaluate the role of regional radiotherapy in women presenting with clinical N1 axillary node disease before neoadjuvant chemotherapy, and who become pathologically node negative at the time of surgery. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the treatment of breast cancer, including opportunities for self-evaluation and board review, please visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

This week's host, Dr. Thomas Karasic, is an assistant professor at University of Pennsylvania specializing in the treatment of gastrointestinal malignancies. In this episode, Dr. Karasic discusses the recent FDA approval of lenvantinib for patients with unresectable hepatocellular carcinoma. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Thomas Karasic, I'm an assistant professor at the University of Pennsylvania, specializing in the treatment of gastrointestinal malignancies. Today, we will discuss the approval of lenvatinib for the treatment of patients with un-resectable hepatocellular carcinoma. As background to our discussion today, the only FDA approved therapy prior to 2017 for hepatocellular carcinoma was sorafenib. This is based on results of the SHARP trial published in the New England Journal in 2008, which demonstrated an overall survival benefit of 10.7 months in the sorafenib arm, versus 7.9 months in the placebo arm. In the 10 years after the approval of sorafenib, a number of phase III trials attempted to establish additional drugs or combination regiments in both the first line and the second line setting for advanced hepatocellular carcinoma. But all trials failed to meet their primary endpoint, and no other treatments were approved. However, in 2017, two new drugs were approved for the second line treatment of hepatocellular carcinoma-- regorafenib, a drug similar to sorafenib, as well as the PD-1 inhibitor, nivolumab. Lenvatinib is an anti-angiogenic tyrosine kinase inhibitor that targets VEGF-1 3, FGFR 1 through 4, PDGFRA, KIT, and RET. On August 16, 2018, lenvatinib was FDA approved for the first line treatment of un-resectable hepatocellular carcinoma. Two different doses were approved-- 12 milligrams for patients with actual body weight greater than or equal to 60 kilograms, and 8 milligrams for patients with actual body weight less than 60 kilograms. The approval of lenvatinib in the first line setting was based on the results of a non-inferiority study comparing lenvatinib to sorafenib for unresectable hepatocellular carcinoma. The primary endpoint of the study was overall survival. A total of 1,492 patients were recruited, and 954 patients were randomized one-to-one between lenvatinib or sorafenib. Lenvatinib was given at a dose of 12 milligrams daily for patients of at least 60 kilograms actual body weight, or 8 milligrams for those below 60 kilograms-- while sorafenib was given at the FDA approved dose of 400 milligrams twice daily. This trial met its primary endpoint of non-inferiority for overall survival. Overall survival was 13.6 months in the lenvatinib arm, and 12.3 months in the sorafenib arm. While it met its endpoint for non-inferiority, it did not establish superiority in terms of overall survival. The hazard ratio for overall survival was 0.92. Lenvatinib did demonstrate a statistically significant increase in time to progression-- 8.9 months in the lenvatinib arm, versus 3.7 months in the sorafenib arm. It also showed a statistically significant improvement in overall response rate. Using the study endpoint of modified RECIST criteria, the objective response rate with lenvatinib was 41% versus 12% with sorafenib. Using more standard RECIST 1.1 criteria, the overall response rate of lenvatinib was 19%, versus 7% with sorafenib. Adverse events were common in both arms of the study, with 57% of those treated with lenvatinib experiencing grade 3 or greater toxicity, compared to 49% of those treated with sorafenib. Toxicities that were more common with lenvatinib included hypertension, proteinuria, hypothyroidism, weight loss, anorexia, nausea, and vomiting-- while sorafenib more commonly had hand/foot syndrome and alopecia. Toxicities, such as fatigue and diarrhea, were similar between the two arms. The approval of lenvatinib marks the first positive front line study comparing an agent to sorafenib in the first line treatment for HCC. Lenvatinib demonstrated improvements in overall response rate, as well as progression-free survival, and a modest trend towards improved overall survival, although this was not statistically significant. The toxicities of sorafenib and lenvatinib were largely comparable, although some toxicities-- such as hand/foot syndrome are more common with sorafenib-- whereas hypertension and proteinuria are more common with lenvatinib. These study results established lenvatinib as a reasonable firstline option for the treatment of HCC, and choice of sorafenib versus lenvatinib can be made based on toxicity profile, as well as the symptoms of the patient that may dictate the need for an agent with a higher response. Pending results from the CheckMate 459 study, as well as other ongoing immunotherapy front line studies, may well change the sequence of immunotherapy and anti-angiogenic therapy for HCC. But for now, lenvatinib is a reasonable front line option. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on lenvatinib and the treatment of hepatocellular carcinoma, visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT Welcome to the Self-Evaluation episode of the ASCO University weekly podcast. My name is Dr. Karen Winkfield, and I am Associate Director for Cancer Health Equity and Director of Hematologic Radiation Oncology at the Comprehensive Cancer Center at Wake Forest Baptist Health in Winston-Salem North Carolina. Today, we feature a self-evaluation question on the treatment of multiple myeloma and other plasma cell dyscrasias, and we begin by reading the question stem. A 65-year-old woman was found to have free light-chains in her urine after she presented with proteinuria. A 24-hour urine collection contained 0.6 grams of monoclonal lambda light-chains, and the urinary sediment was normal. She had normal complete blood count, renal function, and serum lactate dehydrogenase and calcium levels. Serum protein electrophoresis was normal with no monoclonal component. Subsequent free light-chain, or FLC, studies revealed kappa at 68.5 milligram per liter and lambda at 16.7 milligram per liter with FLC ratio of 4.1 with a normal range of 0.26 to 1.65. The bone marrow aspirate revealed 6% of mature-looking plasma cells. Bone marrow biopsies failed to demonstrate any amyloid deposits. Both conventional and fluorescent in situ hybridization cytogenetic analyses were normal. Skeletal X-rays, as well as spinal access MRIs were normal. The diagnosis is light-chain monoclonal gammopathy of undetermined significance, or LC MGUS. Which of the following is an accurate description of this disease? A, around 30% of cases present with kidney disease. B, around 3/10 of 1% per year of cases progress to light-chain multiple myeloma. C, around 30% of all MGUS is comprised of this condition. D, around 3% of the general population older than 50 years has this condition. [MUSIC PLAYING] The correct answer to this question is B, around 3/10 of 1% per year of cases progress to light-chain multiple myeloma. This answer reflects the natural history of LC MGUS. Briefly, the other choices presented in this question are incorrect for the following reasons. Approximately 23% of LC MGUS cases have or will develop renal disease. Therefore, answer A slightly overstates the incidence at 30%. Similarly, LC MGUS comprises only 19% of total cases of MGUS. This is consistent with the proportion of light-chain multiple myeloma cases among newly-diagnosed multiple myeloma patients. An estimated 0.8% of the general population age 50 years and older has LC MGUS. Thank you for listening to this week's episode of the ASCO University weekly podcast. For more information on the treatment of multiple myeloma and other plasma cell dyscrasias, visit the comprehensive E-Learning Center at university.asco.org. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information.