Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial
Won Seog Kim, Tae Min Kim, Seok‐Goo Cho, Isidro Jarque, Elżbieta Iskierka‐Jazdzewska, Li Mei Poon, H. Miles Prince, Huilai Zhang, Junning Cao, Mingzhi Zhang, Benoît Tessoulin, Sung Yong Oh, Francesca Lim, Cecilia Carpio, Tran‐Der Tan, Sabarish Ayyappan, Antonio Gutiérrez, Jingxian Cai, Melanie Ufkin, Saleem Shariff, Jurriaan Brouwer‐Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Jan Walewski, on behalf of the ELM-2 Investigators, Hannah Rose, Geoffrey Chong, Vinod Ganju, Michael Chu, Mary‐Margaret Keating, Yuqin Song, Jun Zhu, Xiaoyan Ke, Shuhua Yi, Huilai Zhang, Qingyuan Zhang, Liqun Zou, Mingzhi Zhang, Dengju Li, Wenbin Qian, Ou Bai, Li Gao, Jie Jin, Caixia Li, Huiqiang Huang, Zheng Wei, Youhua Chen, Pengcheng He, Gandhi Damaj, Kamal Bouabdballah, Emmanuel Bachy, Corinne Haïoun, Franck Morschhauser, Sylvain Choquet, Vincent Delwail, Catherine Thieblemont, Johannes Duell, Thomas Weber, Paul Graf La Rosee, Holger Hebart, Enrico Capochiani, Vittorio Ruggiero Zilioli, Francesca Gaia Rossi, Stefano Luminari, Pier Luigi Zinzani, L Bagnato, Gianluca Gaïdano, Marco Brociner, Cristina Skert, Monica Tani, Roberta Battistini, Leonardo Flenghi, Ryusuke Yamamoto, Kunihiro Tsukasaki, Kenichi Ishizawa, Tomomi Tobai, Toshiki Uchida, Yosuke Minami, Nobuhiko Yamauchi, Junichiro Yuda, Masahiro Takeuchi, Hirokazu Nagai, Youko Suehiro, Yoshiaki Ogawa, Junya Kuroda, Tatsuro Jo, Hirohisa Nakamae, Isao Yoshida, Michał Taszner, Ewa Lech-Maranda, Wanda Knopińska‐Posłuszny, Tomasz Wróbel, Tadeusz Robak, Kuangwen Hsieh, Shin Yeu Ong, Hyeon-Seok Eom, Yeung‐Chul Mun, Young Rok, Jin Seok Kim
Abstract
The phase 2, multicohort, ongoing ELM-2 study evaluates odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma after ≥2 lines of therapy. Here primary analysis of the diffuse large B cell lymphoma (DLBCL) cohort is reported. Patients received intravenous odronextamab in 21-day cycles until progression or unacceptable toxicity, with cycle 1 step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary endpoint was objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS) and overall survival. A total of 127 patients were enrolled. At the 29.9-month efficacy follow-up, the ORR was 52.0% and CR rate was 31.5%. Median durations of response and CR were 10.2 and 17.9 months, respectively. Undetectable minimal residual disease at cycle 4 day 15 was associated with PFS benefit. With a step-up of 0.7 to 4 to 20 mg (n = 60), CRS was the most common treatment-emergent adverse event (53.3% (grade ≥3, 1.7%)). No immune effector cell-associated neurotoxicity syndrome was reported. Infections were reported in 82/127 (64.6%) patients (grade ≥3, 38.6%; coronavirus disease 2019, 18.1% (grade ≥3, 12.6%)). In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care. Clinical trial registration: NCT03888105 .