Therapeutic Advances in Hematology (Jun 2022)

Real-world effectiveness and safety analysis of carfilzomib–lenalidomide–dexamethasone and carfilzomib–dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis

  • Yoshiyuki Onda,
  • Junya Kanda,
  • Hitomi Kaneko,
  • Yuji Shimura,
  • Shin-ichi Fuchida,
  • Aya Nakaya,
  • Tomoki Itou,
  • Ryosuke Yamamura,
  • Hirokazu Tanaka,
  • Hirohiko Shibayama,
  • Yutaka Shimazu,
  • Hitoji Uchiyama,
  • Satoshi Yoshihara,
  • Yoko Adachi,
  • Mitsuhiro Matsuda,
  • Hitoshi Hanamoto,
  • Nobuhiko Uoshima,
  • Satoru Kosugi,
  • Kensuke Ohta,
  • Hideo Yagi,
  • Yuzuru Kanakura,
  • Itaru Matsumura,
  • Masayuki Hino,
  • Shosaku Nomura,
  • Chihiro Shimazaki,
  • Akifumi Takaori-Kondo,
  • Junya Kuroda,

DOI
https://doi.org/10.1177/20406207221104584
Journal volume & issue
Vol. 13

Abstract

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Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib–lenalidomide–dexamethasone (KRd) and carfilzomib–dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.