Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.

Abstract

BACKGROUND:

Combinatory strategies with carfilzomib (CFZ), a second-generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting.

AIMS:

To evaluate the real-world efficacy and safety of CFZ-based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group.

METHODS AND RESULTS:

All 50 patients with RRMM enrolled in this study were treated with CFZ-based treatments between 2017 and 2019. KRD and KD were administered to 31 and 19 patients, respectively. The overall response rates (ORRs) were 80.6% with KRD and 73.7% with KD. Two-year progression-free survival (PFS) and overall survival (OS) were 58.5% and 79.7% with KRD, and 23.1% and 52.6% with KD. By multivariate analysis, refractoriness to BTZ and to LEN were identified as independent unfavorable factors for both PFS and OS. The common non-hematologic AEs included hypertension (42.0%), fever (24.0%), fatigue (24.0%), and infection (16.0%). No serious heart failure was observed. This study is registered as UMIN000025108.

CONCLUSION:

This study suggests the need of the development of novel CFZ-containing strategy which can overcome the refractoriness to BTZ and/or LEN, while both KRD and KD were shown to be mostly feasible in Asian patients in a daily practice setting.

• Authors: Yuka Kawaji-Kanayama, Tsutomu Kobayashi, Ayako Muramatsu, Hitoji Uchiyama, Nana Sasaki, Nobuhiko Uoshima, Mitsushige Nakao, Ryoichi Takahashi, Kazuho Shimura, Hiroto Kaneko, Miki Kiyota, Katsuya Wada, Yoshiaki Chinen, Koichi Hirakawa, Shin-Ichi Fuchida, Chihiro Shimazaki, Yayoi Matsumura-Kimoto, Shinsuke Mizutani, Taku Tsukamoto, Yuji Shimura, Shigeo Horiike, Masafumi Taniwaki, Junya Kuroda, Kyoto Clinical Hematology Study Group (KOTOSG) Investigators
• Journal: Cancer reports (Hoboken, N.J.) (Cancer Rep (Hoboken)) Vol. 5 Issue 2 Pg. e1476 (02 2022) ISSN: 2573-8348 [Electronic] United States
• PMID: 34124862 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.

Chemical References

• Oligopeptides
• Bortezomib
• carfilzomib
• Lenalidomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bortezomib (administration & dosage)
• Drug Resistance, Neoplasm
• Female
• Humans
• Japan
• Lenalidomide (administration & dosage)
• Male
• Middle Aged
• Multiple Myeloma (drug therapy)
• Oligopeptides (administration & dosage)
• Pilot Projects
• Prognosis
• Prospective Studies