Outcomes of younger patients with mantle cell lymphoma experiencing late relapse (>24 months): the LATE-POD study

• Published in: Blood Vol. 144; no. 9; pp. 1001 - 1009
• Main Authors: Malinverni, Chiara, Bernardelli, Andrea, Glimelius, Ingrid, Mirandola, Massimo, Smedby, Karin E., Tisi, Maria Chiara, Giné, Eva, Albertsson-Lindblad, Alexandra, Marin-Niebla, Ana, Di Rocco, Alice, Moita, Filipa, Sciarra, Roberta, Bašić-Kinda, Sandra, Hess, Georg, Ohler, Anke, Eskelund, Christian W., Re, Alessandro, Ferrarini, Isacco, Kolstad, Arne, Räty, Riikka, Quaglia, Francesca Maria, Eyre, Toby A., Scapinello, Greta, Stefani, Piero Maria, Morello, Lucia, Nassi, Luca, Hohaus, Stefan, Ragaini, Simone, Zilioli, Vittorio Ruggero, Bruna, Riccardo, Cocito, Federica, Arcari, Annalisa, Jerkeman, Mats, Visco, Carlo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.08.2024
• Subjects: Adult; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cohort Studies; Disease Progression; Female; Humans; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - mortality; Lymphoma, Mantle-Cell - pathology; Lymphoma, Mantle-Cell - therapy; Male; Medicin och hälsovetenskap; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - therapeutic use; Recurrence; Rituximab - administration & dosage; Rituximab - therapeutic use; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023023525

•Patients with MCL experiencing late relapse benefit from BTK-inhibitors over chemoimmunotherapies.•Overall, chemoimmunotherapies as second-line treatment are discouraged in the era of chimeric antigen receptor T-cell therapies. [Display omitted] 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. Malinverni and colleagues compared outcomes of second-line therapy with Bruton tyrosine kinase inhibitors (BTKis) vs chemoimmunotherapy (CIT) in patients with mantle cell lymphoma (MCL) relapsing >24 months after first-line CIT. In an international cohort study including 10 countries, the evaluation of 385 patients with MCL with late-disease progression demonstrated that BTKi therapy was associated with significantly improved progression-free survival (median not reached [NR] vs 26 months) and overall survival (median NR vs 56 months), suggesting that BTKi is the preferred second-line therapy in the late-relapse setting.