Use of Lenalidomide Plus Rituximab in TP53-Mutated Mantle Cell Lymphoma (MCL) Outside of Clinic Trial: The Moffitt Experience

Introduction

MCL is an incurable B-cell lymphoma, accounting for 3-8% of Non-Hodgkin Lymphoma (NHL). Efforts to increase frontline treatment intensity with cytarabine (AraC), autologous transplant, and prolonged Rituximab maintenance have improved outcomes for many. However, those with TP53 mutations do not show similar benefit, highlighting a need for novel approaches in this setting. Lenalidomide plus Rituximab (R2) has been shown to have activity in MCL, but little data exist in the context of TP53 alterations.

Methods

We retrospectively reviewed 145 patients diagnosed with MCL between 2005 and 2019. Cases were selected by diagnosis of MCL and clinical evaluation from July 2018 to June 2019. A total of 145 unique cases were identified, of which 63 had insufficient testing for TP53, 50 were negative, and 32 were mutation positive by cytogenetics, NGS, or FISH. Patients with mutated TP53 were further assessed for the primary outcome of event-free survival (EFS) and a secondary outcome of overall survival (OS). All statistical analyses were performed using SPSS software.

Results

Of 32 analyzed patients, 72% were male, with median age 67 years (46-87) and median WBC 15 (3-283). All but one patient presented with ECOG PS 0-1. LDH was elevated in 44%, with high MIPI in 56% of patients. Ki67 was available in 8 cases (median 30%), with 2 additional cases noted only as "blastoid."

Frontline therapy consisted of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (RCHOP) or Bendamustine plus Rituximab (BR) with maintenance Rituximab (6 patients), AraC, and/or transplant (8), R2 (8), BTK+Rituximab (2), or palliation (XRT 1, Rituximab 2, watchful waiting 5). Seven patients received R2 in the relapsed setting. With median followup of 44 months, the median OS was not reached (83%), and median EFS among all treated patients was 36 months.

Among those who received frontline R2, 63% were male, with median age 68 (55-75), median WBC 74 (11-283), with elevated LDH in 50% and high MIPI in 88%. Ki67 was available for 2 patients, and measured 10% and 80%. The Median OS and EFS were 100% with median followup on therapy of 15 months.

Conclusions

Survival was surprisingly robust across this cohort of high risk MCL. Treatment with Lenalidomide plus Rituximab may provide an alternative regimen for TP53-mutated MCL in the first-line setting. Further analysis of long-term data will be beneficial to monitor durability of remission.

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