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The phase III ECHO trial evaluated acalabrutinib + bendamustine-rituximab (A+BR) vs placebo + BR in previously untreated mantle cell lymphoma (MCL) patients ≥65 years, showing a significant improvement in progression-free survival (PFS) (66.4 vs 49.6 months) with A+BR, including in high-risk subgroups. Objective response rate (ORR)/complete response (CR) rates were higher with A+BR (91.0%/66.6% vs 88.0%/53.5%), but overall survival (OS) was not significantly different (HR 0.86). Grade ≥3 adverse events (AEs) were similar between arms (88.9% vs 88.2%), with more COVID-19–related events in the acalabrutinib group, likely reflecting longer exposure. Bottom line: adding acalabrutinib to BR gives us a real PFS advantage in older, untreated MCL, with manageable toxicity, but OS benefit remains elusive—likely due to crossover and effective salvage BTKi at relapse.

The ECHO phase III trial evaluated acalabrutinib + bendamustine-rituximab (BR) vs placebo plus BR in untreated mantle cell lymphoma (MCL) patients ineligible for transplant, showing a significant improvement in progression-free survival (PFS) (66.4 vs 49.6 months) with a hazard ratio (HR) of 0.73. The combination achieved a higher overall response rate (ORR) (91.0% vs 88.0%) and complete response (CR) rate (66.6% vs 53.5%), supporting its efficacy in this older population. Of note, side effects like pneumonia, atrial fibrillation, and infections were more frequent with acalabrutinib, with serious adverse effects in 69% versus 62% for placebo. This triplet regimen could redefine first-line treatment for our MCL patients, but we’ll need to stay vigilant about managing toxicities, especially in older patients.

The BOVen regimen of Zanubrutinib, Obinutuzumab and Venetoclax showed impressive results in the TP53+ population, albeit in a small sample size here. This is on NCCN and could be considered the right patient.

Potentially practice changing trial from the EU on young, transplant eligible patients with MCL were all treated with first line chemo then randomized to Auto-HSCT +/- Ibrutinib.  The addition of Ibrutinib to Auto-HSCT improved DFS compared to Auto-HSCT alone, and more interestingly patients treated Ibrutinib was better than those who had transplant but the data on the Ibrutinib vs traplant + Ibrutinib arms are premature.  The addition of maintenance Rituximab did not seem to change any outcomes.