MM-011: A Phase 2 Study of Pomalidomide Plus Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma in Japan
Authors: Hagiwara Shotaro , Okamoto Shinichiro , Matsue Kosei , Iida Shinsuke , Sunami Kazutaka , Komeno Takuya , Suzuki Kenshi , Ando Kiyoshi , Taniwaki Masafumi , Tobinai Kensei , Chou Takaaki , Kaneko Hitomi , Iwasaki Hiromi , Uemura Chie , Tamakoshi Hiromi , Zaki Mohamed H , Doerr Thomas , Kuroda Yoshiaki , Ichinohe Tatsuo 
Published: October 2019

Abstract
Introduction: Pomalidomide plus low-dose dexamethasone (POM + LoDEX) is approved for the treatment of patients with relapsed and refractory multiple myeloma (RRMM). In RRMM, POM + LoDEX significantly prolonged progression-free survival (PFS) compared with POM alone (MM-002; Richardson et al Blood, 2014) and significantly improved PFS and overall survival (OS) compared with high-dose DEX alone (MM-003; San Miguel et al Lancet Oncol, 2013), while demonstrating an acceptable safety profile. In Japanese patients with RRMM, a phase 1 study identified POM 4 mg/day as the tolerated dose (MM-004; Iida ASH 2014), consistent with observations in Caucasian patients. The study presented here, MM-011, was conducted to evaluate the efficacy and safety of POM + LoDEX in Japanese patients with RRMM.
Methods: MM-011 was a multicenter, single-arm, open-label phase 2 study in patients with RRMM. Eligible patients had received ≥ 2 prior therapies, including ≥ 2 cycles of lenalidomide and ≥ 2 cycles of bortezomib (either separately or in combination) and had developed progressive disease on or within 60 days of the last prior therapy. Patients received POM 4 mg orally on days 1-21, and LoDEX orally on days 1, 8, 15, and 22 of each 28-day cycle. LoDEX was given at 40 or 20 mg in patients aged ≤ 75 or > 75 years, respectively. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was overall response rate (ORR; partial response rate [PR] or better) of POM + LoDEX according to the International Myeloma Working Group criteria. The required sample size was calculated using the expected response rate of 25%, the threshold response rate of 10% on 1-sided alpha of 0.05, and the statistical power of 80% based on the test for 1 sample proportion. Thirty-three pts were needed as a result of this calculation.
Results: A total of 36 patients were enrolled. Median age was 64.5 years (range, 43-78 years), and 11% were aged > 75 years. Patients had a high tumor burden (81% had Durie-Salmon stage II or III disease) and were heavily pretreated (median of 6.5 prior anti-myeloma regimens; range, 2-15 regimens). All but 1 patient (97%) were refractory to lenalidomide and 58% were refractory to both lenalidomide and bortezomib.
At the data cutoff (February 3, 2015), 16 patients (44%) remained on treatment. Disease progression was the most common reason for discontinuation (n = 14; 39%). All 36 patients enrolled were evaluable for efficacy. The ORR was 42% (n = 15 [95% CI, 26%-58%]), including complete response in 3% (n = 1) and PR in 39% (n = 14). Median PFS was 10.2 months (median follow-up, 4.6 months), and median OS was not reached (median follow-up, 7.7 months). In the 15 responders, median time to response was 1.9 months and median duration of response was not reached.
The most common grade 3/4 hematologic adverse events (AEs) were neutropenia (n = 23; 64%), anemia (n = 15; 42%), and thrombocytopenia (n = 11; 31%), and the most common grade 3/4 non-hematologic AEs were pneumonia (n = 3; 8%) and decreased appetite (n = 3; 8%). Peripheral neuropathy (any grade) occurred in 8% (n = 3). No deep vein thrombosis or pulmonary embolism was reported. Overall, AEs were similar to those in other POM studies, and no new significant AEs were reported in Japanese RRMM patients. Three patients (8%) had an AE that led to discontinuation. Three patients died on study (or within 28 days of the last dose of study drug). Two of these patients died due to multiple myeloma and 1 due to AE (asthma and pneumonia, suspected to be related to study drug).
Conclusions: POM + LoDEX is an effective regimen in heavily pretreated Japanese patients with RRMM with acceptable safety profiles that are comparable with those of POM studies in RRMM in other regions.

Disclosures
Hagiwara: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Matsue:Celgene Corporation: Honoraria. Iida:Celgene Corporation: Honoraria, Research Funding; Janssen Pharmaceuticals Inc: Honoraria; Kyowa Hakko Kirin Inc: Research Funding; Ono Pharmaceutical Inc: Research Funding; Chugai Pharmaceutical Co: Research Funding; Eli Lilly Inc: Research Funding. Sunami:Ono Pharmaceutical Company, Limited: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding. Ando:Kyowa Hakko Kirin Co., Ltd: Research Funding. Tobinai:Gilead Sciences: Research Funding. Chou:Celgene Corporation: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Ono Pharmaceutical CO., LTD.: Consultancy, Honoraria. Kaneko:Celgene Corporation: Research Funding. Uemura:Celgene Corporation: Employment. Tamakoshi:Celgene Corporation: Employment. Zaki:Celgene Corporation: Employment, Equity Ownership. Doerr:Celgene Corporation: Employment.