Phase 1/2 study of venetoclax, a BCL-2 inhibitor, in Japanese patients with relapsed or refractory chronic lymphocytic l
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ORIGINAL ARTICLE
Phase 1/2 study of venetoclax, a BCL‑2 inhibitor, in Japanese patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma Koji Izutsu1,2 · Kazuhito Yamamoto3 · Koji Kato4 · Takayuki Ishikawa5 · Noriko Fukuhara6 · Yasuhito Terui7 · Ilseung Choi8 · Kathryn Humphrey9 · Su Young Kim10 · Sumiko Okubo11 · Natsumi Ogawa12 · Yasuko Nishimura12 · Ahmed Hamed Salem10 · Dai Maruyama1 Received: 7 May 2020 / Revised: 30 September 2020 / Accepted: 5 October 2020 © Japanese Society of Hematology 2020
Abstract Patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have limited treatment options. Venetoclax is a potent BCL-2 inhibitor that induces apoptosis in CLL cells. This open-label, phase 1/2 study (NCT02265731) evaluated the safety, pharmacokinetics, and efficacy of venetoclax in Japanese patients with R/R CLL/SLL. Patients enrolled in phase 1 received 400 mg/day venetoclax monotherapy. Patients enrolled in phase 2 received 400 mg/day venetoclax, plus rituximab. Venetoclax was administered with a weekly stepwise ramp-up in doses. In phase 2, efficacy was evaluated by objective response rate (ORR). Twelve patients were enrolled, six in each arm. The most common grade ≥ 3 adverse events were neutropenia (83%), lymphopenia (67%), leukopenia (33%), and thrombocytopenia (17%). Patients receiving venetoclax monotherapy achieved an ORR of 100%, including a complete remission (CR) rate of 17%. Patients receiving combination therapy had an ORR of 67% and a CR rate of 50%. The venetoclax pharmacokinetics profile in Japanese patients was similar to that of Western patients. Venetoclax 400 mg/day monotherapy or in combination with rituximab was well-tolerated and induced promising responses in Japanese patients with R/R CLL/SLL. Although patient numbers were small, the safety profile was largely consistent with other Western studies. Clinical trial registration: clinicaltrials.gov; NCT02265731. Keywords BCL-2 · Chronic lymphocytic leukemia · Small lymphocytic lymphoma · Venetoclax
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12185-020-03024-3) contains supplementary material, which is available to authorized users. * Koji Izutsu [email protected] 1
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
2
Department of Hematology, Toranomon Hospital, Tokyo, Japan
3
Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan
4
5
Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan Department of Hematology, Kobe City Medical Center General Hospital, Hyogo, Japan
6
Department of Hematology, Tohoku University Hospital, Sendai, Japan
7
Department of Hematology Oncology, The Cancer Institute Hospital JFCR, Tokyo, Japan
8
Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan
9
Roche Holding AG, Basel, Switzer
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