Prashant Mehta: My thoughts on developments in DLBCL management
Prashant Mehta, Senior Consultant and Assistant Professor in the Department of Medical Oncology/Hematology-oncology and Bone marrow transplantation at the Amrita Hospital, Faridabad, shared a thread on X/Twitter:
“My thoughts on developments in Diffuse Large B Cell Lymphoma (DLBCL) management: Despite several combination studies with R-CHOP, in the last 20 years nothing truly changed in the treatment of DLBCL. 30-40 % of DLBCL are not cured with R-CHOP. Polatuzumab Vedotin is a Monomethyl auristatin E (MMAE)-based Antibody Drug Conjugates (ADCs) targeting CD79B.
Pola-BR showed improved response rates , Progression-free survival (PFS) and Overall Survival (OS) in R/R (relapsed/refractory) DLBCL in transplant ineligible patients thus Pola naturally proceeded to frontline trials. POLARIX tested POLA-R-CHP vs R-CHOP in IPI score 2 or more , DLBCL.
At 24 months there was a significant 6.5 % PFS advantage overall ( 76.6 vs 70.2 %) while 3 year advantage Pola was at 7.7 %. OS was not different. COO evaluation and subset analysis revealed advantage Pola at 29 % in terms of 2 yr PFS ( 85 % vs 56 % )!
In Asian subset a 7.7 % PFS advantage was reported in ASH 2023. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%)
AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). Importantly COO was assessed by Nanostring Lymph2cx assay and not IHC algorithm, so this result has to be applied with great caution in practice if at all.
Phase II GUIDANCE-01 from China has randomised R-CHOP vs R-CHOP-X based on molecular subtype earlier and showed an OS advantage. In time the molecular subtypes will become more defined and the classical Double hit designation will assume less importance.
PHOENIX has shown EFS and OS advantage of adding BTKi to R-CHOP in less than 60 years old. A 2023 update of same shows a subgroup of BCL-2 /MYC overexpression and MYD88 mutation preferentially benefits from BTKi.
A significant association between high BCL2/MYC coexpression and activated B-cell-like and MYD88L265P/CD79B-mutated subtypes of DLBCL has been found.
Overall, though Pola-R-CHP may be an alternative SOC now in intermediate and high risk DLBCL, and may be a preferred option in ABC-DLBCL, BTKi’s may have a place and molecular defined subtypes will become increasingly important in time.
An important consideration for India will be, can Pola become a cost -effective option to prevent relapse and prevent further need for, the still relatively expensive Indian CAR T -cell therapy for a patient. Only time will tell.”
Source: Prashant Mehta/X
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