Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma

•Venetoclax can be added to lenalidomide and rituximab without the occurrence of any dose-limiting toxicity in patients with untreated MCL.•Venetoclax and R2 used as a frontline regimen induced high rates of clinical and molecular responses in patients with untreated MCL. [Display omitted] Mantle ce...

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Published in:	Blood advances Vol. 7; no. 16; pp. 4518 - 4527
Main Authors:	Phillips, Tycel J., Bond, David, Takiar, Radihka, Kump, Karson, Kandarpa, Malalthi, Boonstra, Philip, Mayer, Tera Lynn, Nachar, Victoria, Wilcox, Ryan A., Carty, Shannon A., Karimi, Yasmin H., Nikolovska-Coleska, Zaneta, Kaminski, Mark S., Herrera, Alex F., Maddocks, Kami, Popplewell, Leslie, Danilov, Alexey V.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 22-08-2023 The American Society of Hematology
Subjects:	Adult Bridged Bicyclo Compounds, Heterocyclic - adverse effects Clinical Trials and Observations Humans Lenalidomide - therapeutic use Lymphoma, Mantle-Cell - drug therapy Lymphoma, Mantle-Cell - pathology Rituximab - adverse effects
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Summary:	•Venetoclax can be added to lenalidomide and rituximab without the occurrence of any dose-limiting toxicity in patients with untreated MCL.•Venetoclax and R2 used as a frontline regimen induced high rates of clinical and molecular responses in patients with untreated MCL. [Display omitted] Mantle cell lymphoma (MCL) is a rare, incurable hematological malignancy with a heterogeneous presentation and clinical course. A wide variety of chemotherapy-based regimens are currently used in patients who are untreated. Over the last several years, several targeted or small-molecule therapies have shown efficacy in the relapsed/refractory setting and have since been explored in the frontline setting. Lenalidomide plus rituximab was explored in a phase 2 study of 38 patients with MCL who were untreated and ineligible to receive transplantation, in which the combination produced durable remissions. We looked to build upon this regimen by adding venetoclax to the combination. We conducted a multicenter, open-label, nonrandomized, single-arm study to evaluate this combination. We enrolled 28 unselected patients with untreated disease irrespective of age, fitness, or risk factors. Lenalidomide was dosed at 20 mg daily from days 1 to 21 of each 28-day cycle. The dose of venetoclax was determined using the time-to-event continual reassessment method. Rituximab was dosed at 375 mg/m2 weekly, starting on cycle 1, day 1 until cycle 2, day 1. No dose-limiting toxicities were noted. All patients were treated with venetoclax at the maximum tolerated dose of 400 mg daily. The most common adverse events were neutropenia and thrombocytopenia. The overall and complete response rates were 96% and 86%, respectively. In total, 86% of patients achieved minimal residual disease undetectability via next-generation sequencing. The median overall and progression-free survivals were not reached. The combination of lenalidomide, rituximab, and venetoclax is a safe and effective regimen in patients with untreated MCL. This trial was registered at www.clinicaltrials.gov as #NCT03523975.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2473-9529 2473-9537
DOI:	10.1182/bloodadvances.2023009992