Ibrutinib for relapsed/refractory mantle cell lymphoma: 7-year experience

Abstract

Abstract Background Mantle cell lymphoma (MLC) is nowadays an aggressive and incurable Non-Hodgkin’s lymphoma, characterized by multiple relapses.The persistent activation of B-cell receptor pathway is critical for pathogenesis. Ibrutinib is a potent covalent inhibitor of Bruton’s tyrosine kinase (BTK) that inhibits B-cell antigen receptor signaling downstream of BTK and changed for better how MCL is treated in relapsed/refractory setting. However, resistance is common and response limited. Methods Retrospective analysis and follow-up of all MCL patients treated with Ibrutinib in a Onco-Hematology Department. Results Eleven patients were identified, with a median age of 68 years [58-78], the majority of them were males (83.3%). At diagnosis, 9% were in stage III of Ann Arbor while 81.8% were in stage IV. The median MIPI (MCL International Prognostic Index) was 5.5 [4-8]. These patients were exposed to a median of 3 treatments [3-5]. The majority of them performed as 1oline treatment R-FCM (18.2%) or R-CHOP (54.5%); as 2oline R-CHOP (45.5%), as 3oline Ibrutinib (63.6%), as 4oline PEPC (60%) and as 5oline Ibrutinib (100%). Ibrutinib therapy was prescribed as a 2oline in 9.1% of the patients, as a 3oline in 63.6%, as 4oline in 40% and as a 5oline in 100%. Ibrutinib achieved a complete response rate in 9.1%, a partial response in 45.5% (response rate, RR, of 54.5%), disease progression in 36.4%, stable disease in 9,1%. At the end of the study, 5 patients were alive and still doing Ibrutinib (4 of them in full dose 560 mg/day). The median progression free survival (PFS) was 3 months [1-26]. Overall survival was not reached (3 patients died with disease progression). Conclusions Although a larger sample and a longer follow-up are needed, these data showed worse results when compared to previous phase 2 trials demonstrating a 68% response rate (RR), including for high-risk patients and heavily pretreated. Most recently, a pooled analysis of the three open-label studies of ibrutinib in MCL, PCYC-1104, SPARK, and RAY revealed an ORR of 68%, 63% and 72%. Ibrutinib may be changing the natural history of MCL as many other agents still under development. Enrollment in clinical trials is crucial not only for discovery of new agents and testing combinations but also to understand the natural history of relapsed MCL. Legal entity responsible for the study Onco-Hematology Service of Instituto Portugues de Oncologia do Porto, F.G., E.P.E. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.