A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy

Abstract

Because of high relapse rates with rituximab combinations, there is an unmet need for new therapeutic agents for treatment of indolent B-cell non-Hodgkin lymphoma (iNHL) or follicular lymphoma (FL). In previous trials, ofatumumab in combination with chemotherapy showed good results in relapsed/refractory FL pretreated with rituximab. This phase 3 trial evaluated the efficacy and safety of single-agent ofatumumab vs single-agent rituximab in rituximab-sensitive relapsed FL that relapsed at least 6 months after completing the last prior treatment with single-agent rituximab or a rituximab-containing regimen. Patients were randomized 1:1 to receive either ofatumumab (1000 mg) or rituximab (375 mg/m2) every week for 4 weeks for the induction phase, followed by once every 2 months for 4 additional doses. The primary endpoint, progression-free survival (PFS) and secondary endpoints, overall response rate (ORR) and overall survival (OS), were evaluated. Overall, 438 patients were assigned to receive ofatumumab (n = 219) and rituximab (n = 219). Baseline characteristics were similar in both arms. The independent review committee assessed whether median PFS was shorter in the ofatumumab arm than in the rituximab arm (16.33 vs 21.29 months), with no significant difference (hazard ratio, 1.15; 95% confidence interval, 0.89-1.49; P = .29) and also showed a lower ORR (50%) compared with the rituximab arm (66%). At the time of analysis, data were not matured for OS results. The number of grade >3 adverse events was higher in the ofatumumab arm (37%) than the rituximab arm (28%). Ofatumumab showed no superiority over rituximab in patients with FL who had relapsed after a rituximab-containing therapy. This study was registered at www.clinicaltrials.gov as #NCT01200589.

Conflict of interest statement

Conflict-of-interest disclosure: D.G.M. reports stock options from AZ Biotherapeutics; honoraria from Bioline RX, Kite Pharma, Gilead, Novartis, Juno Therapeutics, Celgene, AZ Biotherapeutics, and Pharmacyclics; research funding from Kite Pharma, Juno Therapeutics, and Celgene; and intellectual property interest from Juno Therapeutics; N.F. reports honoraria from Chugai Pharma, Eisai, Kirin Pharmaceuticals, Janssen, Mochida, Mundi, Nippon Shinyaku, Ono, Takeda, and Zenyaku; a consulting role with Celgene, Chugai, and Ono; and research funding from Celgene, Eisai, AbbVie, Bayer, Gilead, Solasia Pharma, and Takeda; J.D., J.L., and M.I. report they are employees of Novartis and have stock ownership to disclose from Novartis. M.O. reports honoraria from Celgene and MeijiSeika Pharma and a consulting role with Celltrion, Mundi Pharma, Symbio, Verastem, Eisai, Teva Takeda, and Denevo Biopharma; HB is an employee of Novartis; K.T. reports honoraria from Zenyaku Kogyo, Eisai, Takeda, Mundipharma, HUYA Bioscience, Kyowa Kirin, Celgene, Chugai Pharma, Ono Pharmaceutical, Yakult, Daiichi Sankyo, Bristol-Meyers Squibb, Meiji Seika Kaisha, Solasia Pharma, and Verastem; consulting roles with Zenyaku Kogyo, Takeda, Mundipharma, HUYA Bioscience, Celgene, Ono Pharmaceutical, and Daiichi Sankyo; and research funding from Eisai, Takeda, Mundipharma, Kyowa Kirin, Celgene, Chugai Pharma, Ono Pharmaceutical, AbbVie, and Janssen.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Consort diagram.

Figure 2.

Kaplan-Meier PFS. (A) Independent reviewer-assessed Kaplan-Meier PFS (ITT population). (B) Investigator-assessed Kaplan-Meier PFS (ITT population).

Figure 3.

Kaplan-Meier OS.