A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial

Journal of Hematology & Oncology, Jun 2013

Background There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. Methods MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with ≥1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for ≥1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie-Salmon stage III) and were heavily pretreated (56.7% had received ≥4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. Results The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4–18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5–9.8). The most common grade 3–4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. Conclusions Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options. Trial registration China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410.

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A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial

Journal of Hematology & Oncology A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial Jian Hou 3 Xin Du 1 Jie Jin 0 Zhen Cai 0 Fangping Chen 7 Dao-bin Zhou 6 Li Yu 5 Xiaoyan Ke 4 Xiao Li 9 Depei Wu 8 Fanyi Meng 2 Huisheng Ai 11 Jingshan Zhang 12 Honeylet Wortman-Vayn 12 Nianhang Chen 12 Jay Mei 12 Jianmin Wang 10 0 The 1st Hospital, Zhejiang University , Hangzhou , China 1 Guangdong General Hospital , Guangzhou , China 2 Nanfang Hospital of Southern Medicine University in Guangzhou , Guangzhou , China 3 Department of Hematology, Shanghai Changzheng Hospital , Shanghai 200003 , China 4 Peking University Third Hospital , Beijing , China 5 The 301 Hospital-Chinese PLA General Hospital , Beijing , China 6 Peking Union Medical College Hospital , Beijing , China 7 Xiangya Hospital of Central South University , Changsha , China 8 The 1st Affiliated Hospital of Soochow University , Suzhou , China 9 Shanghai 6th Hospital , Shanghai , China 10 Changhai Hospital , Shanghai , China 11 The 307 PLA Hospital , Beijing , China 12 Celgene Corporation , Summit, NJ , USA Background: There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. Methods: MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with 1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for 1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie-Salmon stage III) and were heavily pretreated (56.7% had received 4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. Results: The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4-18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5-9.8). The most common grade 3-4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. Conclusions: Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options. Trial registration: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410. Relapsed/Refractory Multiple Myeloma; Chinese Patients; Lenalidomide; Low-dose Dexamethasone - Introduction In China, the annual incidence of hematological malignancies, including multiple myeloma (MM), is estimated to be approximately 2 per 100,000 people [1-3]. The introduction of innovative therapies, such as proteasome inhibitors and immunomodulatory drugs, has improved the prognosis for MM patients worldwide [4]. The Chinese Multiple Myeloma Working Group treatment guidelines currently recommend bortezomib- and thalidomidecontaining regimens for newly diagnosed MM [5], although only bortezomib has been approved for the treatment of MM in China. As MM patients will eventually relapse or become refractory to current treatments, there is a need for new therapeutic agents to offer more options when this occurs. Lenalidomide in combination with dexamethasone has recently been approved by the Chinese authorities as a treatment for patients with relapsed or refractory MM (RRMM) who have received 1 prior therapy. In this setting, lenalidomide plus high-dose dexamethasone has been shown to be superior to high-dose dexamethasone alone in phase 3 studies [6,7]. The combination regimen has been sho (...truncated)


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Jian Hou, Xin Du, Jie Jin, Zhen Cai, Fangping Chen, Dao-bin Zhou, Li Yu, Xiaoyan Ke, Xiao Li, Depei Wu, Fanyi Meng, Huisheng Ai, Jingshan Zhang, Honeylet Wortman-Vayn, Nianhang Chen, Jay Mei, Jianmin Wang. A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial, Journal of Hematology & Oncology, 2013, pp. 41, 6, DOI: 10.1186/1756-8722-6-41