Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study


Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.

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Fig. 1: Survival curves according to second line therapy.
Fig. 2: Survival curves for patients with early-POD.
Fig. 3: Survival curves for patients with late-POD.
Fig. 4


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The authors are grateful to the patients who participated in the study, their family, friends and caregivers, the study staff and health care providers. The authors thank Benedetta Puccini (Firenze), Annalisa Arcari (Piacenza), Irene Dogliotti (Torino University), Dario Marino (Padova), Michele Merli (Varese), Francesco Piazza (Padova), Massimo Gentile (Cosenza), Matteo Pelosini (Pisa), Giacomo Loseto (Bari), and AnnaLia Molinari (Rimini) who provided data. We thank Emilia Elizbeta Florea (Verona) for the precious administrative support to the research. All authors participated in patients’ enrollment, defined tumor response, and provided information in regard to clinical questions and follow-up. Each contributing center abstracted patient-level data by using criteria defined in the MANTLE-FIRST research proposal using a standardized, investigator-developed data entry form.

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Correspondence to Carlo Visco.

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Visco, C., Di Rocco, A., Evangelista, A. et al. Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study. Leukemia (2020).

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