Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma

Kosei Matsue, Hiromi Iwasaki, Takaaki Chou, Kensei Tobinai, Kazutaka Sunami, Yoshiaki Ogawa, Mari Kurihara, Shuichi Midorikawa, Mohamed Zaki, Thomas Doerr, Shinsuke Iida, Kosei Matsue, Hiromi Iwasaki, Takaaki Chou, Kensei Tobinai, Kazutaka Sunami, Yoshiaki Ogawa, Mari Kurihara, Shuichi Midorikawa, Mohamed Zaki, Thomas Doerr, Shinsuke Iida

Abstract

This phase 1, open-label, dose-escalation study investigated the tolerated dose (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone or pomalidomide plus low-dose dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Twelve patients were enrolled. Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1 and days 3-21 of a 28-day cycle. The tolerated dose of pomalidomide was determined to be 4 mg given on days 1-21 of a 28-day cycle. Efficacy outcomes with pomalidomide plus low-dose dexamethasone were consistent with those of previous studies. Responses (partial response or better) were achieved by three patients (25%; 1 [17%] in Cohort 1 and 2 [33%] in Cohort 2), and the median time to response was 6.4 months overall (9.0 months for Cohort 1 and 4.2 months for Cohort 2). The median progression-free survival was 5.5 months overall (5.1 months for Cohort 1 and not reached for Cohort 2). The most frequently occurring grade ≥3 adverse events were neutropenia (67%), anemia (25%), lymphopenia (25%), and pneumonia (25%), consistent with previous studies of pomalidomide plus low-dose dexamethasone in refractory or relapsed and refractory multiple myeloma. Further investigation of pomalidomide is recommended for Japanese patients with refractory or relapsed and refractory multiple myeloma. This study was registered with ClinicalTrials.gov (NCT01568294).

Keywords: Clinical trial; dexamethasone; multiple myeloma; pharmacokinetics; pomalidomide.

© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Figures

Figure 1
Figure 1
Determination of the tolerated dose of pomalidomide in Japanese patients with refractory or relapsed and refractory multiple myeloma. Patients received pomalidomide 2 mg (Cohort 1) or 4 mg (Cohort 2) orally on day 1 and days 3–21 of a 28‐day cycle. aIn this instance, continuation of the study would be discussed at the ESEC. DLT, dose‐limiting toxicity; ESEC, Efficacy–Safety Evaluation Committee.
Figure 2
Figure 2
Patient disposition for this phase 1, open‐label, dose‐escalation study that investigated the tolerated dose (recommended dose), safety, efficacy, and pharmacokinetics of pomalidomide alone or in combination with low‐dose dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Data cut‐off: November 19, 2013. PD, progressive disease.
Figure 3
Figure 3
Progression‐free survival (PFS) in Japanese patients with refractory or relapsed and refractory multiple myeloma. CI, confidence interval; NE, not estimable; NR, not reached
Figure 4
Figure 4
Plasma concentration of pomalidomide in Japanese patients with refractory or relapsed and refractory multiple myeloma after a single 0.5‐mg dose, single or multiple 2‐mg doses, or single or multiple 4‐mg doses. Mean (± SD) plasma concentration shown. (a) , 4.0 mg; , 2.0 mg; , 0.5 mg. (b) , 4.0 mg; , 2.0 mg.

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