Real-world Data: MCL2 Protocol Demonstrates Excellent Treatment Results Among Patients With Mantle Cell Lymphoma Not Fulfilling the Original Trial Inclusion Criteria

Abstract

Mantle cell lymphoma (MCL) is a rare and heterogeneous subgroup of B-cell lymphomas. The clinical course of MCL varies from an indolent form to an extremely aggressive phenotype. MCL is still an incurable disease. However, intensified chemoimmunotherapy regimens and targeted therapies have increased the overall survival (OS) of patients <65 years old from 5.6 years to 8.9 years. 1 Today, the standard treatment for fit patients <65-70 years is high-dose cytarabine-containing immunochemotherapy regimens followed by autologous stem cell transplantation (ASCT). 2 The MCL2 protocol developed by the Nordic Lymphoma Group is one of these approaches. 3,4 The MCL2 protocol has shown a median OS of 12.7 years at the 15-year follow-up and a median progression-free survival (PFS) of 8.5 years. 4 Similar results have been obtained in other high-dose regimen trials. [5][6][7] This study aimed to evaluate the efficacy of the MCL2 protocol in a population-based retrospective analysis and to compare treatment results in patients fulfilling the trial eligibility criteria with those who would have been trial ineligible.We collected data on patients diagnosed with MCL from 7 hospitals in Finland and 1 hospital in Spain from 2000 to 2020. This study was approved by the Finnish Social and Health Data Permit Authority. In total, 520 patients were included in this study. Of these, 198 patients (38%) received treatment according to the MCL2 protocol (the MCL2 group). The MCL2 protocol started with the induction treatment of rituximabmaxi-CHOP, alternating with rituximab-high-dose-cytarabine. ASCT, preceded by BEAM therapy (carmustine-etoposidecytarabine-melphalan), was used as a consolidation therapy after 6 immunochemotherapy cycles. 3 Rituximab maintenance therapy has been used as an option after ASCT in recent years. The remaining 322 patients (the other group) received rituximab combined with CHOP/CHOP-like regimens, bendamustine, or high-dose cytarabine-based regimens, MCL-FI (a Finnish protocol for elderly patients), 8 single-agent rituximab, or irradiation. To evaluate the impact of the patient selection criteria on survival, we divided the patients treated with the MCL2 protocol into trial-eligible and trial-ineligible subgroups, following the MCL2 trial inclusion criteria, which were an Eastern Cooperative Oncology Group (ECOG) performance test status of 0-2, stage II-IV disease, and age <66 years. 3 To obtain comparable groups, we excluded the patients with missing trial inclusion parameters in all categories. The patient-specific characteristics of the other group, the MCL2 group, and the subgroups of trial-eligible and trial-ineligible patients, along with the actual MCL2 trial, 3 are summarized in Table 1. The median age was higher in the trial-ineligible group (67 years) than in the trial-eligible group (59 years), and Mantle Cell Lymphoma International Prognostic Index (MIPI) high-risk disease was more common in the trial-ineligible group (37.7% versus 20.9%).The MCL subtype was not reported in most pathology reports; ther...