Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study

Abstract

During the Covid-19 pandemic, ibrutinib +/- rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. As limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib +/- rituximab for untreated MCL were evaluated for treatment toxicity, response and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 >/=30%). 149 patients from 43 participating centres were enrolled: 74.1% male, median age 75, 75.2% ECOG 0-1, 36.2% high-risk, 8.9% autologous transplant candidates. All patients received >/= 1 cycle ibrutinib (median 8 cycles), 39.0% with rituximab. Grade >/= 3 toxicity occurred in 20.3%, 33.8% required dose reductions/delays. At 15.6 months (mo) median follow-up, 41.6% discontinued ibrutinib; 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2% respectively. ORR was 77.3% (low-risk) vs. 59.0% (high-risk), p=0.05, and 78.7% (ibrutinib-rituximab) vs. 64.9% (ibrutinib), p=0.13. Median progression-free survival was 26.0mo (all patients); 13.7mo (high-risk) vs. not reached (NR) (low-risk), p=0.004. Median overall survival was NR (all); 14.8mo (high-risk) vs. NR (low-risk), p=0.005. Median post-ibrutinib survival was 1.4mo, longer in 41.9% patients receiving subsequent treatment (median 8.6 vs 0.6mo, p=0.002). Ibrutinib +/- rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

Targeted Therapies in the Treatment of Mantle Cell Lymphoma

“…Longer-term follow-up and survival data are still pending. Lastly, a multi-center, real-world analysis from the United Kingdom assessed front-line ibrutinib with or without rituximab in untreated MCL [64]. Of the 104 patients assessed, the ORR was 71.2%, and the CRR was 20.2%.…”

Targeting BTK in B Cell Malignancies: From Mode of Action to Resistance Mechanisms

“…Intensive chemotherapy regimens, immunotherapy, and autologous stem cell transplantation (ASCT) are commonly employed in young and fit transplant-eligible patients. Notably, the introduction of novel agents has transformed the treatment landscape for MCL; in particular, BTKi have demonstrated significant efficacy, providing a targeted therapy for MCL patients [ 25 , 26 , 27 , 28 ].…”