Clinical outcomes for ibrutinib in relapsed or refractory mantle cell lymphoma in real‐world experience

Abstract

Ibrutinib is highly effective in patients with relapsed or refractory mantle cell lymphoma (MCL) in major clinical trials. Although there has been a dramatic improvement in survival outcomes in the salvage setting, nonresponders to ibrutinib have a bleak prognosis. Therefore, this retrospective study was conducted to identify the most appropriate therapeutic strategy and prognosis‐related factors to predict the response of patients with relapsed or refractory MCL to ibrutinib monotherapy. Thirty‐three consecutive refractory or relapsed MCL patients treated with ibrutinib were analyzed in this study. The median overall survival (OS) and progression‐free survival (PFS) after initiation of ibrutinib were 35.1 months and 27.4 months, respectively. Risk factor analysis showed that high risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI) and nonresponse to ibrutinib at the first three cycles were significantly associated with inferior OS. Poor PFS was associated with high‐risk biologic MIPI, prior bendamustine exposure, and nonresponse to ibrutinib during the first three cycles. After ibrutinib failure, primary nonresponders had poorer OS and PFS than inconsistent responders. The overall response rate for the first salvage therapy was only 33%, with a median TTP of 3.2 months. There was no effective therapeutic strategy except for allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Although ibrutinib responders exhibited favorable survival outcomes, nonresponders had a dismal prognosis. To overcome these limitations, it may be necessary to modify therapeutic strategies, such as selecting inconsistent responders for earlier allo‐HSCT.

Treatment of mantle cell lymphoma in Asia: a consensus paper from the Asian Lymphoma Study Group

“…ORR was 93.8%, with CR seen in 31.3% of patients by the end of the phase II follow-up [78]. Real-world data of ibrutinib monotherapy in a salvage setting in Korea showed a favorable ORR and duration of response; however, higher MIPI and/or prior bendamustine exposure was associated with ibrutinib treatment failure and poorer outcomes [79]. Additional data from a Korean retrospective analysis of 75 patients with advanced MCL treated with ibrutinib reported a 70% ORR; at a median follow-up of 30.5 months, the median PFS was 18.6 months; and among elderly patients, better outcomes from ibrutinib were achieved in second-line versus later lines of therapy (median PFS 24.4 versus 5.8 months; P = 0.015) [80].…”

Safety and efficacy analysis of ibrutinib in 32 patients with CLL and various B-cell lymphomas: real-world data from a single-center study in Turkey

“…Ibrutinib is indicated for CLL as well as for many B-cell lymphomas [26][27][28][29] [30]. In other studies, the ORR was 48.0% in patients with MZL, 37.5% in patients with FL, and 90.0% in patients with WM [28,31,32].…”

Ibrutinib in B-cell lymphoma: single fighter might be enough?

“…Unlike ibrutinib monotherapy in CLL/SLL, it might not be enough for patients with MCL. A real-world study indicated a median OS and PFS after ibrutinib monotherapy in R/R MCL patients were 35.1 months and 27.4 months, respectively [21]. This might be interpreted by the biological differences and more complex cross-action signaling pathways in MCL patients.…”

“…This might be interpreted by the biological differences and more complex cross-action signaling pathways in MCL patients. Therefore, ibrutinib monotherapy might not be the best choice for this population and other choices such as combination strategies followed by stem cell transplantation might be favorable for them [21].…”