Long-Term Use of Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Chinese Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): MM-024 Expanded Access Program (EAP)
Authors: Du Xin , Jin Jie , Cai Zhen , Chen Fangping , Zhou Dao-bin , Yu Li , Ke Xiaoyan , Li Xiao , Wu Depei , Meng Fanyi , DeMarco Dena , Zhang Jingshan , Mei Jay , Hou Jian 
Published: October 2019

Abstract
Introduction: In China, the Rd regimen is approved for use in multiple myeloma (MM) pts who have received ≥ 1 prior treatment (Tx). This approval was based on the efficacy and safety of Rd demonstrated in the MM-021 study, a phase 2 multicenter registration trial in which 199 pts were enrolled (Hou, J Hematol Oncol 2013). MM-024 is both an EAP and an extension study that was initiated in order to provide continued Rd regimen for pts enrolled in the MM-021 study. Updated safety and efficacy information from the EAP is presented here.
Methods: Eligible pts had participated in MM-021, were still on Tx for ≥ 1 year (yr) and were progression-free. Pts received the same regimen of Rd as in MM-021 (lenalidomide 25 mg/day on days 1–21, and low-dose dexamethasone 40 mg/day on days 1, 8, 15, and 22 of each 28-day cycle). The starting doses of Rd were the same as the last doses received in MM-021 unless dose adjustments were required prior to rollover, as per protocol. Tx was continued until progressive disease (PD) or withdrawal due to toxicities, and pts were followed-up for a maximum of 5 yrs (which included 1 yr spent in the MM-021 study). The primary endpoint was safety, including the incidence of second primary malignancy (SPM). Secondary endpoints included progression-free survival (PFS), time to progression (TTP), and overall survival (OS).
Results: By the cutoff date (May 5th, 2014), of the 41 pts who entered the Tx phase of the EAP, 21 are still receiving Tx with a median number of 22 cycles. A total of 20 pts discontinued Tx: 18 discontinued due to PD; 1 due to death (related to lung infection); and 1 was lost to follow-up. Median follow-up was 37.5 months (mos) from initial enrolment in the MM-021 study. Median age was 59 yrs (range 47–74) and 34% of pts were aged > 65 yrs. Most pts (78%) had Durie-Salmon stage III disease at baseline. All pts had received prior Tx for MM, including thalidomide and bortezomib; 7.3% of pts had undergone surgery and 2.4% of pts had received radiation therapy. The median number of prior Tx was 3 (range 1–11); 76% of pts had received prior bortezomib, 68% had received prior thalidomide, and 46% had received both. Median duration of Rd Tx was 21.6 mos (range 13.1–37.5) and 22% of pts have received > 25 mos of the regimen. All efficacy endpoints were measured from the enrolment date of the MM-021 study. Median PFS and median TTP were both 36.0 mos. Median OS has not been reached due to the low number of deaths. Overall, 48.8% of pts had grade 3–4 treatment-emergent adverse events (TEAEs); the most common TEAEs were anemia (51.2%), decreased neutrophil count (48.8%), upper respiratory tract infection (41.5%), neutropenia (31.7%), cough (24.4%), diarrhea (22.0%), and pyrexia (22.0%). Grade ≥ 3 TEAEs included neutropenia (14.6%), anemia (4.9%), thrombocytopenia (2.4%), and pneumonia (7.3%). No TEAEs led to Tx discontinuation; however, TEAEs led to lenalidomide dose reduction (14.6%), interruption (39%), or both (14.6%). Updated efficacy, survival, and SPM analysis will be presented at the meeting.
Conclusions: After 37.5 mos of follow-up, median PFS was 36 mos, compared with the median PFS of 7.5 mos in the MM-021 final analyses (cutoff date January 4th, 2013). This indicates that long-term use of Rd is well tolerated and continues to be an effective Tx in Chinese pts with RRMM who have received multiple prior Tx.

Disclosures
DeMarco: Celgene Corporation: Employment. Zhang:Celgene Corporation: Employment. Mei:Celgene Corporation: Employment. Hou:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees.