Mantle Cell Lymphoma Can Be Cured by Intensive Immunochemotherapy with In-Vivo Purged Stem-Cell Support; Final Report of the Nordic Lymphoma Group MCL2 Study.

Mantle cell lymphoma (MCL) is considered incurable, with a median survival of 4 years. Intensive immunochemotherapy and autologous stem-cell (ASC) support has appeared promising in small patient cohorts, but has not been tested in large, consecutive series. Here we report the final results of the 2^nd Nordic MCL (MCL2) trial after a median of 3 years follow-up from study entry.

Methods: This unrandomized phase-II trial included 159 untreated patients younger than 66 years, 84% stage IV, 128 with classical, 31 with blastoid/pleomorphic cytology. Following 6 cycles of intensive induction immunochemotherapy with alternating cycles of rituximab (R) + maxi-CHOP and R+ high-dose AraC, responders received BEAM/BEAC with in-vivo purged (R) ASC support.

Results: 153 patients (96%) responded to induction therapy with CR in 55% and PR in 41%. The 5-year event-free (EFS) and overall survival (OAS) are 63% and 74% respectively on intention-to-treat, and the 144 (91%) responders who completed treatment had 72% 5-year response duration, with plateaus emerging in all three curves at these levels.

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There were 6 treatment-related deaths (3,8%). Of 77 patients with available primers, 90% had become PCR-negative two months posttransplant; those who remained PCR-negative more than 1 year posttransplant had a significantly longer clinical response duration than patients who did not (P<0.0001). Of 42 stem-cell products assessed 88% were PCR-negative as compared to only 12% in the MCL1 study (P<0.001). In a multivariate analysis including age, sex, international prognostic index (IPI), cytological variants and Ki-67 proliferation index, only IPI and Ki-67 were independent predictors of EFS and response duration respectively, and only IPI and cytological variant of OAS. Compared to the 41 patients of 1^st Nordic MCL study who received 4 cycles of maxi-CHOP without rituximab before BEAM or BEAC + ASCT (1), the OAS, EFS and response duration were highly significantly increased.

Conclusion: The demonstration of long-term event-free survival in a large, consecutive prospective series now for the first time indicates that intensive immunochemotherapy including AraC and Rituximab with in-vivo purged stem-cell support may cure mantle cell lymphoma.