A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial.

Abstract

Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.

• Authors: Ken Ohmachi, Tomohiro Kinoshita, Kensei Tobinai, Gakuto Ogawa, Tomonori Mizutani, Nobuhiko Yamauchi, Noriko Fukuhara, Toshiki Uchida, Kazuhito Yamamoto, Kana Miyazaki, Norifumi Tsukamoto, Shinsuke Iida, Takahiko Utsumi, Isao Yoshida, Yoshitaka Imaizumi, Takashi Tokunaga, Shinichiro Yoshida, Yasufumi Masaki, Tohru Murayama, Yoshihiro Yakushijin, Youko Suehiro, Kisato Nosaka, Nobuaki Dobashi, Junya Kuroda, Yasushi Takamatsu, Dai Maruyama, Kiyoshi Ando, Kenichi Ishizawa, Michinori Ogura, Tadashi Yoshino, Tomomitsu Hotta, Kunihiro Tsukasaki, Hirokazu Nagai, Japan Clinical Oncology Group
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 4 Pg. 984-993 (02 23 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 33591324 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cyclophosphamide (therapeutic use)
• Doxorubicin (therapeutic use)
• Humans
• Lymphoma, Large B-Cell, Diffuse (drug therapy)
• Prednisone (therapeutic use)
• Rituximab (therapeutic use)
• Vincristine (therapeutic use)