WolverHeme Happy Hour

In this enlightening episode, Anthony and Bernie chat about FLT3+ AML with Dr. Dale Bixby, Clinical Professor and expert in leukemia at the University of Michigan. We use two clinical cases to take a deep dive into the biology and prognostic implications of FLT3+ AML, pitfalls and controversies of variant allele frequency and allelic ratio testing, and the data that informs the use of FLT3 inhibitors in AML. Watch out for some possibly heretical views! REFERENCES Schlenk and Dohner (Impact of AML prognostic markers)l: https://pubmed.ncbi.nlm.nih.gov/19468271/ RATIFY Trial: https://www.nejm.org/doi/full/10.1056/nejmoa1614359 QUANTUM-FIRST: https://library.ehaweb.org/eha/2022/eha2022-congress/356965/harry.erba.quizartinib.prolonged.survival.vs.placebo.plus.intensive.induction.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Amarker%3D1749%2Afeatured%3D17676 ODAC Review of Quantum-R (quizartinib): https://www.fda.gov/media/124896/download ELN 2022: https://pubmed.ncbi.nlm.nih.gov/35797463/ WHO Myeloid 2022: https://pubmed.ncbi.nlm.nih.gov/35732831/ Sorafenib Maintenance (RCT China): https://pubmed.ncbi.nlm.nih.gov/32791048/ SorMAIN: https://pubmed.ncbi.nlm.nih.gov/32673171/ RADIUS (midostaurin maintenance): https://pubmed.ncbi.nlm.nih.gov/33288862/ LACEWING Trial: https://pubmed.ncbi.nlm.nih.gov/35917453/ HMA/Ven pooled FLT3: https://pubmed.ncbi.nlm.nih.gov/35063965/ Ven/Aza/Gilteritinib ASH 2022: https://ash.confex.com/ash/2022/webprogram/Paper157210.html UK NCRI AML 17 Flt3 analysis: https://pubmed.ncbi.nlm.nih.gov/27268085/

After a refreshing break, the hosts dive into the fascinating pharmacology behind major AML therapies. They discuss the iconic '3 plus 7' chemotherapy regimen and its lasting impact. Historical insights on anthracyclines reveal their evolution and crucial studies on effectiveness. The conversation also covers the unique journey of cytarabine, exploring its origins and complex administration challenges. Lastly, advancements in purine analogs shed light on new treatment strategies, especially for older patients. Beverages and personal anecdotes add a fun twist to the serious topics!

In this episode, Bernie and Anthony do an in-depth dive into the pharmacology, toxicity management, and clinical conundrums with asparaginase therapy, including how and when to monitor asparaginase activity levels (per Papa Heme request!). For those who don't know (and maybe aren't as nerdy as we are), the title is a reference to the 1964 film Dr. Strangelove!

In this episode, Bernie Marini and Anthony Perissinotti chat with special guest Charles Foucar, MD, a hematology specialist and expert in the field. We discuss the controversial FDA approval of ivosidenib in combination with azacitidine in newly diagnosed IDH1+ AML, based on the results of the AGILE study: https://www.nejm.org/doi/full/10.1056/NEJMoa2117344

In this episode, Bernie Marini and Anthony Perissinotti are joined by two special guest hematology experts - Lydia Benitez, PharmD, BCOP, and Madeleine Ochs, PharmD, BCOP. Maddy and Lydia help us dive into the topic of Oncology Stewardship, including how we can incorporate Oncology Stewardship into practice to improve outcomes for patients.  Learn more about Oncology Stewardship in AML patients in our hot off the press paper in Annals of Hematology, written by Maddy (first author), Lydia (senior author), and the rest of our leukemia team: https://link.springer.com/article/10.1007/s00277-022-04872-1

In part two of this two-part episode, Bernie Marini and Anthony Perissinotti discuss the use of rituximab in acute lymphoblastic leukemia (ALL), based on the recent publication of the UKALL14 study (Marks, et al. Lancet Haematol, 2022): https://pubmed.ncbi.nlm.nih.gov/35358441/. We also discuss the previously published GRAALL study that evaluated rituximab in ALL (Maury, et al. NEJM, 2016, https://pubmed.ncbi.nlm.nih.gov/27626518/), and what we can conclude from the literature to date. The data surprises us, and makes us question our own practices!

In part one of a two-part episode, Bernie Marini and Anthony Perissinotti take a journey through the history of acute lymphoblastic leukemia treatment throughout the decades and explain how we got to our current standard of care treatment of ALL patients. In part 2 we tackle the UKALL14 study evaluating the addition of rituximab to acute lymphoblastic leukemia therapy. Some important historical articles that we reference: Nitrogen mustard therapy: https://pubmed.ncbi.nlm.nih.gov/20997191/ Methotrexate/Aminopterin: https://www.nejm.org/doi/full/10.1056/nejm194806032382301 Vincristine: https://pubmed.ncbi.nlm.nih.gov/13627916/ and https://pubmed.ncbi.nlm.nih.gov/2085431/ and https://www.utpjournals.press/doi/pdf/10.3138/cbmh.17.1.155 6-MP: https://pubmed.ncbi.nlm.nih.gov/13105700/ Total Therapy: https://pubmed.ncbi.nlm.nih.gov/5237796/ and https://pubmed.ncbi.nlm.nih.gov/5279904/ BFM: https://pubmed.ncbi.nlm.nih.gov/320377/ and https://pubmed.ncbi.nlm.nih.gov/23700050/ This episode is dedicated to the late Don Pinkel (9/7/1927 - 3/9/2022), a pioneer in the treatment of childhood ALL. Read more about his legacy here: https://cancerletter.com/obituary/20220318_4/ and https://www.nature.com/articles/s41375-022-01562-9.pdf and https://www.smithsonianmag.com/innovation/childhood-leukemia-untreatable-dr-don-pinkel-st-jude-180959501/

Bernie Marini and Anthony Perissinotti discuss asparaginase, the data (or lack thereof) behind the FDA approval of Rylaze (Erwinia asparaginase), and concerning trends regarding switches between asparaginase products in clinical practice! 

Bernie Marini and Anthony Perissinotti discuss the following paper on whether or not event-free survival (EFS) is an appropriate surrogate endpoint for overall survival (OS) in AML: Norsworthy KJ, et al. Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses. J Clin Oncol. 2022 Mar 10;40(8):847-854. PMID: 34890212.