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Dr. Weijun- A Multi-Center, Open-Label Phase II Study of Lenalidomide Plus Low-Dose Dexamethasone in Chinese Patients with Relapsed/Refractory Multiple Myeloma - the MM-021 Trial
Fu Weijun, MD
The Myeloma & Lymphoma Center, Changzheng Hospital, The Second Military Medical University
Shanghai, China
Program: Oral and Poster Abstracts
Session: 653. Myeloma - Therapy, excluding Transplantation: Poster I
Saturday, December 8, 2012, 5:30 PM-7:30 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)

Jian Hou, MD, PhD1*, Jie Jin, MD2, Zhen Cai3*, Fangping Chen4*, Li Yu5*, Dao-bin Zhou, MD6*, Xiao Li, MD, PhD7, Xiaoyan Ke, MD, PhD8*, Depei Wu, MD9*, Huisheng Ai10*, Fanyi Meng, MD11, Jianmin Wang12, Jay Mei, MD, PhD13, Jingshan Zhang, PhD13*, Honeylet Wortman-Vayn13* and Xin Du, PhD14

1Department of Hematology, Chang Zheng Hospital, Second Military Medical University, Shanghai, China
2Department of Hematology, Institute of Hematology, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
3The First Affiliated Hospital, Zhejiang University, Hangzhou, China
4Hematology, Xiang Ya Hospital - CSU, Dept. of Hematology, Changsha, China
5Dept. of Hematology, Chinese PLA General Hospital, Beijing, China
6Hematology, Peking Union Medical College Hospital, Beijing, China
7Hematology, Sixth Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
8Hematology, Peking University Third Hospital, China
9Department of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China
10The 307 PLA Hospital, Beijing, China
11Department of hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guang Dong, China
12Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China
13Celgene Corporation, Summit, NJ
14Department of Hematology, Guangdong Provincial People Hospital, Guangzhou, China

Background: Previous studies (i.e. ECOG E4A03) have shown that lenalidomide plus low-dose dexamethasone (Rd) has a better safety profile compared with lenalidomide plus high-dose dexamethasone (RD) in newly diagnosed MM patients. It is hypothesized that Rd may also provide benefits in patients with relapsed/refractory multiple myeloma (RRMM). The MM-021 trial is the largest study in Chinese patients with RRMM aimed to assess the efficacy, safety, and pharmacokinetics (PK) of Rd in patients who had progressed or were refractory to previous treatment.

Methods: This was a phase II, multi-center, single arm, open-label study, RRMM patients received lenalidomide (25 mg/day on days 1-21) and dexamethasone (40 mg on days 1, 8, 15 and 22) in 28-day treatment cycles until disease progression. Thromboembolic prophylaxis with aspirin or other anti-thrombotic medication was required. The primary endpoint was the best overall response rate (partial response [PR] or better) based on the investigator’s assessment. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), safety, and PK parameters.

Results: As of April 23, 2012 (median follow-up of 10.8 months), 199 patients have completed at least 1 cycle, 134 patients have completed at least 6 cycles, and 187 patients were evaluable for efficacy. Median age was 59 years (range 35–81) and 63% were male. The majority of patients (86%) had Durie-Salmon stage III disease and 57% had received ≥4 prior anti-myeloma regimens including bortezomib (64%), thalidomide (69%), or both bortezomib and thalidomide (45%). After median treatment duration of 8 months (range 1–18) or 8 cycles (range 1–19), best overall response rate (≥PR) was 54% (100 patients); including 8% (14 patients) with a best response of complete response (CR). Overall disease control (≥stable disease [SD] or better) was 95%, including 42% (78 patients) with best response of SD. Nine patients (5%) had best response of disease progression. Best overall response rates were consistent across subgroups when analyzed according to baseline renal function (creatinine clearance ≥60 mL/min: 68 patients [54%], ³30 to <60 mL/min: 26 patients [52%], <30 mL/min: 6 patients [50%]) and number of prior therapies (64% if ≤2 prior regimens, 50% if >2 prior regimens). Responses were also consistent regardless of prior therapy received; 50%, 52%, and 47% for patients who previously received bortezomib, thalidomide, or both, respectively. Of the 5% (10 patients) presenting with IgD at baseline, 7 patients achieved ≥PR. Median time to first response was 2 months (range 1–12) and median duration of response was 7 months (range 0–16). The median PFS was 8 months (95% CI: 6–9) and the OS rate was 86% at 6 months and 73% at 1 year. Among the 199 patients evaluable for safety, the most common grade 3–4 adverse events (AEs) were anemia (25%), neutropenia (24%), thrombocytopenia (15%), and pneumonia (13%). Only 1 patient experienced febrile neutropenia. AEs led to dose reduction/interruption of lenalidomide in 40% of patients, 41% for dexamethasone; and 6.5% discontinued treatment due to one or more AEs. No patient discontinued due to anemia or neutropenia. Sixty-one patients (31%) died on study and the most common cause of death was disease progression (15 patients, 8%).

Conclusions: Based on a median follow-up of nearly 11 months, the Rd regimen achieved a substantial best overall response rate (54%) in heavily pretreated RRMM Chinese patients. Response rates were consistent across subgroups including patients with renal impairment. The combination of Rd regimen was generally well tolerated.

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