Risk-adaptive venetoclax therapy improves outcomes in high-risk mantle cell lymphoma.
Tailoring therapy to disease biology and adding fixed duration venetoclax dramatically improves outcomes for high-risk older patients with mantle cell lymphoma, new trial data shows.
The researchers say their multicentre V-RBAC study is the first to use upfront risk stratification in older, transplant-ineligible patients, proving that aggressive disease features can be partially overcome with targeted consolidation after shortened chemoimmunotherapy.
Their findings have been published in The Lancet Haematology.
The trial enrolled 140 patients, 39% of whom carried high-risk markers such as blastoid morphology, high Ki-67 proliferation, or TP53 mutation or deletion.
Low-risk patients received standard six cycles of R-BAC, while high-risk patients had only four cycles followed by venetoclax consolidation and maintenance.
Complete responses were achieved in 91% of low-risk patients versus 61% of high-risk patients, and venetoclax boosted two-year progression-free survival in the high-risk cohort to 58%, well above historical expectations.
Treatment was generally tolerable, with the most frequent grade 3 or worse adverse events during venetoclax consolidation being neutropenia (12 [28%] of 43 patients), followed by thrombocytopenia (three [7%]) and skin reactions (three [7%]).
During venetoclax maintenance, the most frequent grade 3 or worse adverse events were neutropenia (seven [19%] of 37 patients), followed by thrombocytopenia (two [5%]) and anaemia (two [5%]).
One (1%) of 140 patients had a treatment-related death (tumour lysis syndrome during first induction with RBAC in a patient with a high-risk profile).
After nearly three years, two-year progression-free survival across the cohort reached 75%, with overall survival at 80%. Blastoid morphology and TP53 mutation remained the strongest predictors of relapse, highlighting the importance of accurate biomarker testing.
The researchers said the major limitation of their study was the absence of a randomised design, “which could have provided more definitive information on the relevance of venetoclax in this setting, the post-hoc nature of some analyses, and small numbers of patients in the subgroup analyses”.
“On the whole, our results point out the importance of identifying patients with high-risk disease at the time of initial diagnosis and show that an upfront definition of the risk status of patients might allow for timely risk-adapted treatment selection,” they concluded.
“Multiple trials are now underway, including the administration of chimeric antigen receptor T-cell therapy as initial treatment, to establish which approach might substantially improve the survival of patients with high-risk disease.
“The favourable outcomes of the FIL_V-RBAC trial suggest that a consolidation strategy could be an effective option for patients with high-risk mantle cell lymphoma.”
