Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study.

Autor:	Davids MS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachuetts. matthew_davids@dfci.harvard.edu., Roberts AW; Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.; Department of Medical Biology, University of Melbourne, and Walter and Eliza Hall Institute, Melbourne, Australia., Kenkre VP; Division of Hematology and Medical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Wierda WG; Department of Leukemia, MD Anderson Cancer Center, Houston, Texas., Kumar A; Division of Hematology and Oncology, University of Arizona Cancer Center, Tuscon, Arizona., Kipps TJ; Division of Hematology-Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, San Diego, California., Boyer M; F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom., Salem AH; AbbVie Inc., North Chicago, Illinois., Pesko JC; AbbVie Inc., North Chicago, Illinois., Arzt JA; AbbVie Inc., North Chicago, Illinois., Mantas M; AbbVie Inc., North Chicago, Illinois., Kim SY; AbbVie Inc., North Chicago, Illinois., Seymour JF; Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.; Department of Medical Biology, University of Melbourne, and Walter and Eliza Hall Institute, Melbourne, Australia.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Sep 01; Vol. 27 (17), pp. 4690-4695. Date of Electronic Publication: 2021 Jun 03.
DOI:	10.1158/1078-0432.CCR-20-4842
Abstrakt:	Purpose: We previously reported a 44% overall response rate (ORR) with the oral BCL-2 inhibitor venetoclax in a phase I study of relapsed/refractory non-Hodgkin lymphoma (NHL). Complete response (CR) was observed in patients with mantle cell lymphoma [(MCL), 21%, n = 6/28] and follicular lymphoma [(FL), 17%, n = 5/29], and partial response (PR) noted in several patients with Waldenström macroglobulinemia (WM), and marginal zone lymphoma (MZL). Here, we report the long-term outcomes of these four cohorts. Patients and Methods: All patients ( n = 106) received venetoclax monotherapy in dose cohorts of 200 to 1,200 mg daily until disease progression or unacceptable toxicity. ORR, progression-free survival (PFS), duration of response (DoR), and adverse events (AEs) were evaluated. Results: At a median follow-up of 38.5 months (range, 30.0-46.5), the median PFS for all 106 patients was 5.4 [95% confidence interval (CI), 3.5-8.4] months (FL, 10.8; MCL, 11.3; MZL, 21.2; and WM, 30.4). The median DoR was 14.9 (95% CI, 9.7-27.6) months (FL, 26.6; MCL, 15.7; MZL, 20.1; and WM, 25.3). Achievement of CR versus PR predicted longer DoR in both MCL (31.5 vs. 10.1 months) and FL (37.6 vs. 9.7 months). All grade hematologic AEs were infrequent: neutropenia (19%), anemia (19%), and thrombocytopenia (17%), with no new cytopenias after 2 years on therapy. Nonhematologic AEs included nausea (49%), diarrhea (46%), fatigue (44%), with decreased incidence after 1 year. Conclusions: Venetoclax monotherapy has a manageable safety profile and achieves durable responses in a subset of patients with FL, MCL, WM, and MZL, particularly in those who achieve CR. Further research is warranted on combination strategies to enhance the durability of response to venetoclax. (©2021 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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