Blood Cancer Talks

In this episode, we discuss the management of acquired aplastic anemia with Dr. Amy DeZern. Here are the links to some of the key articles discussed in this show:1. Review article on aplastic anemia: https://www.nejm.org/doi/10.1056/NEJMra1413485 2. RCTs testing whether addition of cyclosporine to ATG improves outcomes in aplastic anemia:https://www.nejm.org/doi/10.1056/NEJM199105093241901https://www.sciencedirect.com/science/article/pii/S0006497120489748 3. RCT testing horse versus rabbit ATG in aplastic anemia:https://www.nejm.org/doi/full/10.1056/nejmoa1103975 4. Single-arm study of eltrombopag in addition to standard immunosuppressive therapy in aplastic anemia: https://www.nejm.org/doi/10.1056/NEJMoa1613878 5. Long-term follow up of patients treated with immunosuppressive therapy and eltrombopag:https://ashpublications.org/blood/article/139/1/34/476916 6. RACE Trial: Standard immunosuppressive therapy +/- eltrombopag in aplastic anemia:https://www.nejm.org/doi/10.1056/NEJMoa2109965 7. Clinical and molecular determinants of clonal evolution in patients with aplastic anemia:https://ascopubs.org/doi/abs/10.1200/JCO.22.00710

1.     Phase III ASAP trialhttps://ash.confex.com/ash/2022/webprogram/Paper159962.html  2.     Phase III Dauno-Double Trialhttps://ash.confex.com/ash/2022/webprogram/Paper157126.html  3.     Reduced venetoclax exposure: https://ash.confex.com/ash/2022/webprogram/Paper165464.html  4.    Menin Inhibitors in AML https://ash.confex.com/ash/2022/webprogram/Paper164849.htmlhttps://ash.confex.com/ash/2022/webprogram/Paper167412.html  5.    Imetelstat in MDS: IMerge Phase 2https://ash.confex.com/ash/2022/webprogram/Paper169050.html  6.    MOMENTUM: Momelotinibhttps://ash.confex.com/ash/2022/webprogram/Paper162783.htmlHow I manage anemia related to myelofibrosis and its treatment regimens https://link.springer.com/article/10.1007/s00277-023-05126-4

In this episode, we discuss the management of newly diagnosed DLBCL with Dr. Pallawi Torka. We also have a few bonus ASH22 updates on DLBCL. Links to articles and abstracts discussed in the episode are as follows: 1. A comprehensive review article on DLBCL:https://pubmed.ncbi.nlm.nih.gov/33657296/ 2. RCT testing CHOP vs Three Intensive Regimens in DLBCL:https://www.nejm.org/doi/full/10.1056/nejm199304083281404  3. RCT testing R-CHOP vs CHOP in DLBCL in older adults:https://www.nejm.org/doi/full/10.1056/nejmoa011795  4. RCT testing R-CHOP vs CHOP in young (MINT):https://pubmed.ncbi.nlm.nih.gov/21940214/  5. PHOENIX trial: R-CHOP +/- Ibrutinib:https://pubmed.ncbi.nlm.nih.gov/30901302/ 6. R-CHOP +/- Lenalidomide (ECOG-ACRIN E1412):https://pubmed.ncbi.nlm.nih.gov/33555941/  7. R-CHOP vs Pola-R-CHP (POLARIX Trial):https://www.nejm.org/doi/full/10.1056/NEJMoa2115304 8. Comparison of 3 IPI scores in DLBCL:https://ashpublications.org/blood/article/135/23/2041/452696 9. RCT testing R-CHOP vs Dose-Adjusted R-EPOCH (CALGB 50303):https://ascopubs.org/doi/full/10.1200/JCO.18.01994 10. Timing of CNS Prophylaxis in DLBCL:https://pubmed.ncbi.nlm.nih.gov/34995350/ 11. RCT testing R-CHOP vs R-CHOP + Bortezomib (REMoDL-B):https://pubmed.ncbi.nlm.nih.gov/30948276/ 12. Interim PET in DLBCL? https://ashpublications.org/bloodadvances/article/5/9/2375/475850 13. RCTs in Limited Stage DLBCL: CHOP x 8 vs CHOP x 3 + XRT (S8736):https://ascopubs.org/doi/10.1200/JCO.2015.65.4582 CHOP x 4 + Rituximab x 6 vs R-CHOP x 6 (FLYER):https://pubmed.ncbi.nlm.nih.gov/31868632/ PET-adapted therapy with R-CHOP (S1001):https://pubmed.ncbi.nlm.nih.gov/32658627/ 14.   ASH 2022 updates:REMoDL-B update: https://ashpublications.org/blood/article/140/Supplement%201/1770/493225 Glofitamab update: https://ashpublications.org/blood/article/140/Supplement%201/1062/491024 Epcoritamab update: https://ashpublications.org/blood/article/140/Supplement%201/9443/488543

1.      Excellent paper on harmonization of performing and reporting MRD in multiple myeloma:          https://www.nature.com/articles/s41375-020-01012-42.     Does CR really matter in the era of MRD? Landmark paper from the Spanish Group:         https://pubmed.ncbi.nlm.nih.gov/35560160/3.     Meta-analysis showing individual-level prognostic impact of MRD on long-term outcomes in multiple myeloma:        https://pubmed.ncbi.nlm.nih.gov/33284948/4.     MASTER Trial-The first trial testing MRD-adapted treatment strategy in multiple myeloma :         https://pubmed.ncbi.nlm.nih.gov/34898239/

Study showing the time from diagnosis of AML to the start of intensive treatment indicate that a treatment delay has no negative prognostic impact. https://ashpublications.org/blood/article/136/7/823/460669/Does-time-from-diagnosis-to-treatment-affect-the RATIFY clinical trial showing the addition of midostaurin (FLT3 inhibitor) to 7+3 chemotherapy for AML https://www.nejm.org/doi/full/10.1056/nejmoa1614359 Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the European LeukemiaNet (ELN) https://ashpublications.org/blood/article/140/12/1345/485817/Diagnosis-and-management-of-AML-in-adults-2022 ASH 2022 abstract presenting Daunorubicin 60 Vs 90 mg/m2 https://ash.confex.com/ash/2022/webprogram/Paper157126.html ALFA-0701. The addition of gemtuzumab ozogamicin, an anti-CD33 antibody conjugate, to the standard treatment for patients with acute myeloid leukemiahttps://www.thelancet.com/article/S0140-6736(12)60485-1/fulltext Quizartinib data presented at EHA 2022 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 International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemiashttps://ashpublications.org/blood/article/140/11/1200/485730/International-Consensus-Classification-of-Myeloid The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasmshttps://www.nature.com/articles/s41375-022-01613-1  CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.2017.77.6112?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed  Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remissionhttps://www.nejm.org/doi/full/10.1056/NEJMoa2004444

1. GEM-CESAR and ASCENT Trials: Intensive Treatment Strategy in High-Risk Smoldering Multiple Myelomahttps://ash.confex.com/ash/2022/webprogram/Paper159606.htmlhttps://ash.confex.com/ash/2022/webprogram/Paper168930.html 2. What are the odds of having BMPC≥10% in a person with MGUS? IstopMM answers this question by developing a prediction model.https://ash.confex.com/ash/2022/webprogram/Paper170166.htmlLink to the model: https://istopmm.com/riskmodel/ 3. RCT comparing Rd (continuous) vs Rd induction-Mel140-AHCT-R Maintenance in transplant-eligible older adults (60-75 years) with newly diagnosed multiple myeloma https://ash.confex.com/ash/2022/webprogram/Paper159357.html 4. Talquetamab: Phase 1/2 results from Monumental-1https://tinyurl.com/kwn9en9mhttps://www.nejm.org/doi/full/10.1056/NEJMoa2204591 5. MALDI-TOF Mass Spect for Monoclonal Free Light Chain Assessment: A promising candidate for MRD testing in AL amyloidosishttps://tinyurl.com/yrvjjruv 6. Randomized Phase IV REAL Trial (VMP vs Rd) in New Diagnosed Transplant-Ineligible Myelomahttps://tinyurl.com/bde84xuw 7. Teclistamab-Daratumumab-Lenalidomide combination in earlier lines of therapy: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Studyhttps://ash.confex.com/ash/2022/webprogram/Paper159711.html 8. Three excellent abstracts from IstopMM:Is MGUS associated with autoimmune disease?https://tinyurl.com/5dafcz2wIs isolated hypercalcemia in a person with MGUS worrisome for transformation into myeloma?https://tinyurl.com/4tut3reaIs MGUS associated with CKD?https://tinyurl.com/34swvkj9 9. Outcome of patients with high-risk cytogenetic abnormalities in a secondary analysis of MASTER and Dara-VRD arm of GRIFFIN trialshttps://tinyurl.com/2n78yzfh 10. Surrogacy between PFS and OS in Multiple Myelomahttps://ash.confex.com/ash/2022/webprogram/Paper163855.htmlhttps://pubmed.ncbi.nlm.nih.gov/36495317/

ALPINE Trial: Zanubrutinib vs Ibrutinib in Relapsed/Refractory CLL (https://www.nejm.org/doi/full/10.1056/NEJMoa2211582) CLL2-Give Trial: Updated results Obinutuzumab (G), Ibrutinib (I), and Venetoclax (Ve) triplet in Untreated Patients with CLL with 17p Deletion/TP53 Mutation (https://ash.confex.com/ash/2022/webprogram/Paper163245.html)  AVO Trial: Acalabrutinib, Venetoclax, Obinutuzumab (AVO) in a Population of Previously Untreated Patients with CLL Enriched for High-Risk Disease (https://ash.confex.com/ash/2022/webprogram/Paper168003.html)  Watch-and-Wait RCT in Follicular Lymphoma: Long-term follow-up of Phase 3 Study of Rituximab Versus a Watch and Wait Approach for Patients with Asymptomatic, Low Tumour Burden Follicular Lymphoma (https://ash.confex.com/ash/2022/webprogram/Paper156790.html) Augment Trial: Update of Phase 3 RCT comparing Rituximab-Revlimid (R2) vs Rituximab-Placebo in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (https://ash.confex.com/ash/2022/webprogram/Paper158631.html) TRIANGLE Study: Ibrutinib Combined with Standard First-Line Treatment or As Substitute for Autologous Stem Cell Transplantation in Younger Patients with Mantle Cell Lymphoma (https://ash.confex.com/ash/2022/webprogram/Paper163018.html) 

Excellent overview of Castleman Disease: https://ashpublications.org/blood/article/135/16/1353/452573/Overview-of-Castleman-diseaseInternational consensus guideline for treatment of Idiopathic Multicentric Castleman Disease (iMCD): https://ashpublications.org/blood/article/132/20/2115/39506/International-evidence-based-consensus-treatmentSomatic alterations in Castleman Disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624446/https://www.nature.com/articles/s41375-018-0323-6Rituximab + Liposomal Doxorubicin in HHV8-positive MCD: https://ashpublications.org/blood/article/124/24/3544/33494/Rituximab-plus-liposomal-doxorubicin-in-HIVRCT on Siltuximab for MCD: https://pubmed.ncbi.nlm.nih.gov/25042199/Long-term data on Siltuximab in MCD: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30257-1/fulltext

In this episode, we discussed the three CD19-directed chimeric antigen receptor (CAR T-cell) therapies that have been approved for relapsed/refractory aggressive large B cell lymphomas (LBCL) after two lines of therapy: Axicabtagene ciloleucel (axi-cel) https://www.nejm.org/doi/full/10.1056/nejmoa1707447Tisagenlecleucel (tisa-cel) https://www.nejm.org/doi/full/10.1056/nejmoa1804980Lisocabtagene maraleucel (lisocel)https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31366-0/fulltext2.  Next, we delved into the three prospective phase 3 randomized clinical trials that were conducted to define the optimal second-line treatment by comparing each of the CAR T-cell products to the current standard of careZUMA-7 for axicabtagene ciloleucel https://www.nejm.org/doi/full/10.1056/NEJMoa2116133BELINDA for tisagenlecleucel https://www.nejm.org/doi/full/10.1056/NEJMoa2116596TRANSFORM for lisocabtagene maraleucel https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00662-6/fulltext3. Then, we briefly discussed the preliminary studies of CAR-T cell therapy in front-line therapy for large B cell lymphomaAxicabtagene ciloleucel (axi-cel) https://www.nature.com/articles/s41591-022-01731-4

Key articles and trials discussed in the episode:1.      Excellent review in NEJM on treatment of CLL (2020): https://www.nejm.org/doi/full/10.1056/NEJMra19082132.     Alliance Trial (Ibrutinib vs chemoimmunotherapy in older patients with untreated CLL): https://www.nejm.org/doi/full/10.1056/NEJMoa18128363.     E1912 (Ibrutinib vs chemoimmunotherapy in younger/fit patients with CLL): https://www.nejm.org/doi/full/10.1056/NEJMoa18170734.     RCT testing Acalabrutinib vs Ibrutinib (non-inferiority) in relapsed CLL: https://ascopubs.org/doi/10.1200/JCO.21.012105.     ELEVATE-TN Study (Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab): https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30262-2/fulltext6.     CLL-11 trial (showed that obinutuzumab>rituximab in CLL): https://www.nejm.org/doi/full/10.1056/nejmoa13139847.      Initial data from German CLL-13 trial: https://ashpublications.org/blood/article/138/Supplement%201/71/477548/A-Randomized-Phase-III-Study-of-Venetoclax-Based8.    Ventricular arrhythmia and sudden death with BTK inhibitor: https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2022016953/486090/Ventricular-Arrhythmias-and-Sudden-Death-Events?redirectedFrom=fulltext\9.    CLL14 trial (venetoclax-obinutuzumab in untreated CLL): https://www.nejm.org/doi/full/10.1056/nejmoa181528110.  Extended follow-up and MRD dynamics in CLL14 trial: https://ascopubs.org/doi/10.1200/JCO.21.0118111.   CAPTIVATE Study on fixed-duration Ibrutinib-venetoclax in newly diagnosed CLL: https://ashpublications.org/blood/article/139/22/3278/484114/Fixed-duration-ibrutinib-plus-venetoclax-for-first12.   Ibrutinib-Venetoclax for treatment of CLL: https://www.nejm.org/doi/full/10.1056/nejmoa190057413.   GLOW study (Ibrutinib-Venetoclax vs Chlorambucil-Obinutuzumab): https://evidence.nejm.org/doi/abs/10.1056/EVIDoa2200006