Outcomes of younger patients with mantle cell lymphoma experiencing late relapse (>24 months): the LATE-POD study
C. Malinverni, Andrea Bernardelli, Ingrid Glimelius, Massimo Mirandola, Karin E. Smedby, Maria Chiara Tisi, Eva Giné, Alexandra Albertsson-Lindblad, Ana Marín‐Niebla, Alice Di Rocco, Filipa Moita, Roberta Sciarra, Sandra Bašić‐Kinda, Georg Heß, Anke Ohler, Christian Winther Eskelund, Alessandro Re, Isacco Ferrarini, A. Kolstad, Riikka Räty, Francesca Maria Quaglia, Toby A. Eyre, Greta Scapinello, Piero Maria Stefani, Lucia Morello, Luca Nassi, Stefan Hohaus, Simone Ragaini, Vittorio Ruggero Zilioli, Riccardo Bruna, Federica Cocito, Annalisa Arcari, Mats Jerkeman, Carlo Visco
Abstract
ABSTRACT: Patients with mantle cell lymphoma (MCL) who experience first relapse/refractoriness can be categorized into early or late progression-of-disease (POD) groups, with a threshold of 24 months from MCL diagnosis. Bruton tyrosine kinase inhibitors (BTKi) are the established standard treatment at first relapse, but their effectiveness compared with chemoimmunotherapy (CIT) in late-POD patients remains unknown. In this international, observational cohort study, we evaluated outcomes among patients at first, late POD beyond 24 months. The primary objective was progression-free survival from the time of second-line therapy (PFS-2) of BTKi vs CIT. Overall, 385 late-POD patients were included from 10 countries. Their median age was 59 years (range, 19-70), and 77% were male. Median follow-up from the time of second-line therapy was 53 months (range, 12-144). Overall, 114 patients had second-line BTKi, whereas 271 had CIT, consisting of rituximab-bendamustine (R-B; n = 101), R-B and cytarabine (R-BAC; n = 70), or other regimens (mostly cyclophosphamide-hydroxydaunorubicin-vincristine-prednisone]- or platinum-based; n = 100). The 2 groups were balanced in clinicopathological features and median time to first relapse. Overall, BTKi was associated with significantly prolonged median PFS-2 than CIT (not reached [NR] vs 26 months, respectively; P = .0003) and overall survival (NR and 56 months, respectively; P = .03). Multivariate analyses showed that BTKi was associated with lower risk of death than R-B and other regimens (hazard ratio, 0.41 for R-B and 0.46 for others), but similar to R-BAC. These results may establish BTKi as the preferable second-line approach in patients with BTKi-naïve MCL.