Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial

Swetha Kambhampati, Bita Fakhri, Weiyun Z. Ai, Lawrence D. Kaplan, Joseph M. Tuscano, Matthew J. Wieduwilt, Akshay Sudhindra, Erika Cavallone, Jesika Reiner, Charlie Aoun, Miguel Castillo, Michelle Martinelli, Teresa Ta, Diem Le, Michelle Padilla, Erika Crawford, Charalambos B. Andreadis

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1 Scopus citations

Abstract

Introduction: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination. Patients and Methods: The protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3. Results: Ten patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m2, and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months. Conclusion: Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options. This is a phase I dose-escalation trial testing the combination of carfilzomib with bendamustine and rituximab in patients with relapsed or refractory non-Hodgkin lymphoma. One dose-limiting toxicity, febrile neutropenia, was observed. The overall response rate was 40%, and the complete response rate was 30%. This novel treatment combination is safe with preliminary efficacy in the mantle cell lymphoma, follicular lymphoma, and plasmablastic lymphoma subtypes.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalClinical Lymphoma, Myeloma and Leukemia
Volume21
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Mantle cell lymphoma
  • Proteasome inhibitor
  • Refractory lymphoma
  • Relapsed lymphoma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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