OUTCOMES IN FIRST RELAPSED‐REFRACTORY YOUNGER PATIENTS WITH MANTLE CELL LYMPHOMA: RESULTS FROM THE MANTLE‐FIRST STUDY

Abstract

Introduction: Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population with poor outcome, where no standard therapy exists. There is a paucity of large-scale data in relapsed or refractory (r/r) MCL. Methods: MANTLE-FIRST, an international, retrospective study, evaluated outcomes in patients with MCL who had progressive disease or first relapse when treated upfront with high dose cytarabine (HDAC), followed by autologous stem cell transplantation if appropriate. Response rates, overall survival (OS), and progression-free survival (PFS) were estimated from the time of initiation of salvage therapy. The previously defined threshold of 24 months since MCL initial diagnosis was used to define patients as having early- or late- first relapse or progression (POD). Results: Overall, 258 patients with r/r MCL were included, with a median follow-up from time of relapse or progression of 38 months (range 1-122). Second line regimens consisted of rituximab bendamustine (R-B) in 22%, rituximab, bendamustine, cytarabine (R-BAC) in 29%, ibrutinib in 18%, and other regimens in 31%. Overall response rate was higher in ibrutinib and R-BAC treated patients (79% for both), as compared to R-B (62%), or other regimens (30%). Complete response (CR) were significantly higher in patients treated with R-BAC (63%) than with R-B (43%, p=0.02), ibrutinib (34%, p=0.002), or other approaches (22%, p<0.0001). Median OS and PFS for all patients were 34±5 and 13±8 months, respectively. PFS curves according to second line therapy are shown in Figure 1. For patients with early-POD (n=126), outcomes were consistently poor, irrespectively of administered second line therapy (median OS 10±1 months), unless for those receiving allogeneic transplant (n=27, median OS 63±24 months). Ibrutinib was associated with longer PFS and OS (10±1 and 30±13, respectively), compared to immunochemotherapy (6±2 and 12±2 months, p=0.09 and p=0.08). For patients with late-POD (n=132), median OS was 74±9 months, and PFS was 34±5. Ibrutinib (not reached), R-BAC (not reached) and R-B (73±21) had similar significant OS advantage, compared to other regimens (41±11, p=0.03). Ibrutinib and R-BAC had similar PFS of 52±18 and 53±22 months, respectively, while R-B was associated with shorter PFS of 31±3 months, although not statistically significant, and other regimens with median PFS of 13±1 months (p<0.0001). At multivariate analysis, factors significantly and independently associated to a reduction of the risk of death were achievement of CR after second line regimens (HR 0,19), allogeneic transplant (HR 0,40), ibrutinib second line therapy (HR 0,47) and late-POD (HR 0,49). Keywords: Bendamustine; ibrutinib; mantle cell lymphoma (MCL).