Outcomes of Younger Patients with Mantle‐cell Lymphoma Experiencing Late Relapse (>24 Months): the LATE‐POD Study

Introduction: Patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) have poor outcome. Time to first relapse or progression (POD) has been consistently shown to be an independent predictor of survival, with patients experiencing early-POD, within 2 years since the diagnosis, representing a subgroup at greater risk of death. On the contrary, there is a paucity of large-scale treatment data on patients experiencing relapse beyond 2 years (late-POD). Methods: In this international, observational cohort study, we evaluated the outcomes amongst patients with first R/R MCL and late-POD, after upfront standard regimens including high dose cytarabine. Patients treated upfront with Bruton tyrosine kinase inhibitors (BTKi) were excluded. The primary objective was progression-free survival (PFS) of BTKi versus chemoimmunotherapy (CIT) as second line therapy. For sample size calculation 100 patients treated with drug 1 (BTKi), and 200 with drug 2 (CIT) were needed to compare PFS of drug 1 versus drug 2, assuming that CIT and BTKi would have a median PFS of 36 and 60 months, respectively. After accrual, all patients were prospectively followed-up. Overall survival (OS-2) and PFS-2 were estimated from the time of salvage therapy. Results: Overall, 386 late-POD patients were included from 10 countries. Median age was 59 (19–70), and 77% were males. Median follow-up from time of first relapse was 53 months (12–144). Overall, 114 patients had second-line BTKi (drug 1), while CIT (drug 2) was delivered to 271 patients, consisting of rituximab-bendamustine (R-B, n = 101), R-B and cytarabine (R-BAC, n = 70), or other regimens (mostly CHOP or platinum-based, n = 100). The two groups were balanced for clinicopathological features, and median time to first relapse (48 months for both). Overall, BTKi was associated with significantly longer median PFS-2 than CIT [51 versus 26 months, respectively, P = 0.0003, Figure 1], and OS-2 [88 and 56 months, P = 0.03]. The performance of BTKi and R-BAC were similar, both in terms of PFS-2 and OS-2, and significantly superior to R-B or other regimens (P = 0.0003, and P = 0.01, respectively). Multivariate Cox regression showed that ibrutinib was associated with inferior risk of death than R-B and other regimens (HR 2.41 for R-B, 2.17 for others), but similar to R-BAC. Blastoid variant, age, and time to POD as continuous variable were also independent predictors of OS-2. Nine patients with TP53 mutation had inferior OS-2 compared to TP53 wild-type patients (n = 48, P = 0.04). The research was funded by: The research was funded in part by Janssen, as part of a Clinical IIS Research Application Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies, Molecular Targeted Therapies No conflicts of interests pertinent to the abstract.