Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas

Soham D. Puvvada, José Guillen-Rodriguez, Abhijeet Kumar, Lora Inclán, Kara Heard, Xavier I. Rivera, Faiz Anwer, Jonathan H Schatz, Daruka Mahadevan, Daniel O. Persky

Research output: Contribution to journalArticle

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Abstract

The combination of bortezomib, cladribine, and rituximab is novel and effective in mantle-cell and indolent non-Hodgkin lymphomas. Background Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). Patients and Methods Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles. Results Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients. Conclusion VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalClinical Lymphoma, Myeloma and Leukemia
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2018

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Cladribine
Mantle-Cell Lymphoma
Non-Hodgkin's Lymphoma
Disease-Free Survival
Bortezomib
Rituximab
Febrile Neutropenia
Therapeutics

Keywords

  • Clinical trial
  • Non-Hodgkin's lymphoma
  • Systemic therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas. / Puvvada, Soham D.; Guillen-Rodriguez, José; Kumar, Abhijeet; Inclán, Lora; Heard, Kara; Rivera, Xavier I.; Anwer, Faiz; Schatz, Jonathan H; Mahadevan, Daruka; Persky, Daniel O.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 18, No. 1, 01.01.2018, p. 58-64.

Research output: Contribution to journalArticle

Puvvada, Soham D. ; Guillen-Rodriguez, José ; Kumar, Abhijeet ; Inclán, Lora ; Heard, Kara ; Rivera, Xavier I. ; Anwer, Faiz ; Schatz, Jonathan H ; Mahadevan, Daruka ; Persky, Daniel O. / Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced, Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas. In: Clinical Lymphoma, Myeloma and Leukemia. 2018 ; Vol. 18, No. 1. pp. 58-64.
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abstract = "The combination of bortezomib, cladribine, and rituximab is novel and effective in mantle-cell and indolent non-Hodgkin lymphomas. Background Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). Patients and Methods Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles. Results Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46{\%} had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17{\%} of patients, of which 8{\%} was grade 3 or above. The overall response rate was 92{\%}. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82{\%} for the MCL group and 54{\%} for the iNHL group; it was 80{\%} for treatment-naive patients and 57{\%} for R/R patients. Conclusion VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL.",
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AU - Guillen-Rodriguez, José

AU - Kumar, Abhijeet

AU - Inclán, Lora

AU - Heard, Kara

AU - Rivera, Xavier I.

AU - Anwer, Faiz

AU - Schatz, Jonathan H

AU - Mahadevan, Daruka

AU - Persky, Daniel O.

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N2 - The combination of bortezomib, cladribine, and rituximab is novel and effective in mantle-cell and indolent non-Hodgkin lymphomas. Background Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). Patients and Methods Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles. Results Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients. Conclusion VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL.

AB - The combination of bortezomib, cladribine, and rituximab is novel and effective in mantle-cell and indolent non-Hodgkin lymphomas. Background Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL) are incurable heterogeneous diseases characterized by relapse. There is a need for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R) setting. We therefore investigated the novel combination of bortezomib (Velcade), cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL (NCT00980395). Patients and Methods Eligible patients included adults with biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment. Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5, and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6 cycles. Results Twenty-four patients were enrolled onto the study with a median follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most common adverse events were hematologic, with febrile neutropenia in 3 patients. Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The overall response rate was 92%. For the entire cohort, and for MCL patients, the median progression-free survival and the median overall survival were not reached. The 2-year progression-free survival was 82% for the MCL group and 54% for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R patients. Conclusion VCR is effective in MCL and iNHL. Although hematologic toxicity can be an issue, this study demonstrates a high response rate to a novel combination and provides an alternative option in transplant-ineligible R/R MCL and iNHL.

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