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

Clinical Cancer Research - Tập 27 Số 17 - Trang 4690-4695 - 2021
Matthew S. Davids1, Andrew W. Roberts2,3, Vaishalee P. Kenkre4, William G. Wierda5, Abhijeet Kumar6, Thomas J. Kipps7, Michelle Boyer8, Ahmed Hamed Salem9, John C. Pesko9, Jennifer A. Arzt9, Margaret Mantas9, Su Y. Kim9, John F. Seymour2,3
11Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachuetts.
22Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia.
33Department of Medical Biology, University of Melbourne, and Walter and Eliza Hall Institute, Melbourne, Australia.
44Division of Hematology and Medical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
55Department of Leukemia, MD Anderson Cancer Center, Houston, Texas.
66Division of Hematology and Oncology, University of Arizona Cancer Center, Tuscon, Arizona.
77Division of Hematology-Oncology, Department of Medicine, University of California San Diego Moores Cancer Center, San Diego, California.
88F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom.
99AbbVie Inc., North Chicago, Illinois.

Tóm tắt

Abstract 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.

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Clinical Cancer Research

Tập 27 Số 17

4690-4695

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