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Clinical Trial
. 2017 Mar;108(3):461-468.
doi: 10.1111/cas.13166.

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan

Kenshi Suzuki  1 , Masaki Ri  2 , Takaaki Chou  3 , Isamu Sugiura  4 , Naoki Takezako  5 , Kazutaka Sunami  6 , Tadao Ishida  1   7 , Tohru Izumi  8 , Shuji Ozaki  9 , Yoshihisa Shumiya  10 , Kenji Ota  10 , Shinsuke Iida  2
Affiliations
Clinical Trial

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan

Kenshi Suzuki et al. Cancer Sci. 2017 Mar.

Abstract

This is the first study in which the carfilzomib, lenalidomide and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM) patients. The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics of the regimen. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m2 , followed by 27 mg/m2 . Lenalidomide and dexamethasone were administered at 25 mg (days 1-21) and 40 mg (days 1, 8, 15 and 22), respectively. Twenty-six patients were enrolled. Patients had received a median of four prior regimens and 88.5% and 61.5% received previous bortezomib and lenalidomide, respectively. High-risk cytogenetics were seen in 53.8% of patients. The overall response rate was 88.5%. A higher rate of hyperglycemia was observed than in a previous carfilzomib monotherapy study, but this was attributed to dexamethasone. Carfilzomib pharmacokinetics were not affected by lenalidomide and dexamethasone. The KRd regimen was well tolerated and showed efficacy in Japanese RRMM patients.

Keywords: Japan; carfilzomib; dexamethasone; lenalidomide; multiple myeloma.

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Figures

Figure 1
Figure 1
Waterfall plot showing the maximum percentage change in the amount of M‐protein for each patient. Data are not shown for one patient because of a limited number of time points where M‐protein was measurable.
Figure 2
Figure 2
Change in M‐protein over time for each patient. Data are not shown for 1 patient because of a limited number of time points where M‐protein was measurable. aUrine M‐protein. BJP, Bence Jones protein; KRd, carfilzomib + lenalidomide + dexamethasone regimen; PR, partial response.
Figure 3
Figure 3
Subgroup analysis for overall response rate. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; KRd, carfilzomib + lenalidomide + dexamethasone regimen.
Figure 4
Figure 4
Carfilzomib plasma concentration‐time profile following a 10‐min intravenous infusion of carfilzomib (mean + standard deviation; first cycle).
See this image and copyright information in PMC

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