Blood Cancer Talks

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

Key papers discussed in the show: 1.     Pediatric regimen for older adolescents and young adults with ALL: CALGB 10403 https://ashpublications.org/blood/article/133/14/1548/260519/A-pediatric-regimen-for-older-adolescents-and2.     Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: C19802 https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.276173.     Rituximab in B-ALL https://www.nejm.org/doi/full/10.1056/NEJMoa16050854.     A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients with Newly Diagnosed Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia: SWOG 1318 https://ascopubs.org/doi/abs/10.1200/JCO.21.017665.     Blinatumomab for MRD in adults with B-ALL https://ashpublications.org/blood/article/131/14/1522/36655/Blinatumomab-for-minimal-residual-disease-in6.     Ph-like ALL https://www.nejm.org/doi/10.1056/NEJMoa1403088

Key papers discussed in the show:1. Landmark paper on HLA-mismatch and survival: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568127/2. HLA-DP and Risk of GVHD: https://www.nejm.org/doi/full/10.1056/NEJMoa15001403. Outcomes of Allogeneic Transplant with HLA-Mismatched Unrelated Donor: https://ascopubs.org/doi/10.1200/JCO.20.035024. Review/perspective on fundamentals of unrelated donors and cord blood units: https://ashpublications.org/blood/article/120/2/259/30405/A-perspective-on-the-selection-of-unrelated-donors5. HLA-DQ heterodimers and HCT: https://ashpublications.org/blood/article-abstract/139/20/3009/484363/HLA-DQ-heterodimers-in-hematopoietic-cell6. PT-Cy as GVHD prophylaxis after HCT: https://pubmed.ncbi.nlm.nih.gov/20124511/7. Comparative outcome of MUD vs Haplo-HCT from Registry data: https://ashpublications.org/blood/article/138/3/273/475738/HLA-haploidentical-vs-matched-unrelated-donor 

In this episode, we do a thought provoking discussion with Dr. Marty Tallman on mentorship and career development in academic hematology and medical oncology. A must listen for all trainees and early career clinical investigators. Sage wisdom from a legend in the field!

2021 European LeukemiaNET MRD Working Party Consensus Guidelines: https://pubmed.ncbi.nlm.nih.gov/34724563/Pre-MEASURE Study ASCO 2022: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.7006

https://ascopubs.org/doi/abs/10.1200/JCO.22.00495

In this episode, we discuss with Dr. Surbhi Sidana the latest advances, practical aspects of patient management, and future directions of cellular therapies in multiple myeloma.