Ixazomib With or Without Rituximab Following Maintenance Autologous Stem Cell Transplant in Mantle Cell Lymphoma: A Single-Center Phase I Trial.

Autor: Romancik JT; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Chen Z; Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL; Biostatistics Shared Resource Core, University of Illinois Cancer Center, Chicago, IL., Allen PB; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Waller EK; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Valla K; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Colbert A; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Rosand C; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Palmer AF; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA., Flowers CR; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX., Cohen JB; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: jonathon.cohen@emory.edu.
Jazyk: angličtina
Zdroj: Clinical lymphoma, myeloma & leukemia [Clin Lymphoma Myeloma Leuk] 2022 Dec; Vol. 22 (12), pp. e1084-e1091. Date of Electronic Publication: 2022 Aug 24.
DOI: 10.1016/j.clml.2022.08.013
Abstrakt: Background: Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard first-line treatment for fit patients with mantle cell lymphoma (MCL). We conducted a single-center phase I trial investigating post-transplant maintenance with ixazomib, an oral proteasome inhibitor.
Methods: Patients enrolled between days +70 and +180 post ASCT. Patients received ixazomib per dose cohort on days 1, 8, and 15 of each 28-day cycle for up to 10 cycles. During recruitment, published phase III data reported a survival benefit with rituximab maintenance, so all subsequent patients received ixazomib 4 mg at the same schedule along with rituximab 375 mg/m 2 on day 1 of cycles 1, 3, 5, 7, and 9. All patients were in complete remission at enrollment.
Results: Seven patients received ixazomib monotherapy; 1 dose limiting toxicity (grade 3 neutropenia) occurred at dose level 2 (4 mg). Five patients received combination Ixazomib plus rituximab, with 2 experiencing DLTs (both Grade 4 neutropenia). Grade 3-4 neutropenia, lymphopenia, and thrombocytopenia occurred in 57%, 8%, and 8% of patients, respectively. Non-hematologic adverse events (AE) included nausea (42%), peripheral neuropathy (42%), and abdominal discomfort (33%), all of which were grade 1 or 2 in severity. There were no infectious AEs. With a median follow up of 46 months, all patients are alive and in complete remission.
Conclusion: The trial was closed to further accrual due to high rates of treatment-related myelosuppression. The current dose and schedule of ixazomib, especially when combined with rituximab, results in unacceptable hematologic toxicity when administered as post-transplant maintenance in MCL. Ixazomib maintenance micro abstract: The authors conducted a phase I study investigating the use of ixazomib, an oral proteasome inhibitor, with or without rituximab in patients with mantle cell lymphoma in first remission following chemoimmunotherapy and autologous stem cell transplantation. All patients treated on study remain in complete remission with a median follow-up of 46 months, but the study was closed early due to a high rate of hematologic adverse events.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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