Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
multiple myeloma, Biological, antibodies, Adult, Diseases, Therapies, Plasma Cell Disorders, Lymphoid Malignancies, Study Population
Methods: Eligible pts in LEPUS and CASTOR received ≥1 prior line of therapy and were randomized 2:1 in LEPUS and 1:1 in CASTOR to 8, 21-day cycles of V (1.3 mg/m2 SC) on Days 1, 4, 8, and 11, and d (20 mg, PO or IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 ± D (16 mg/kg IV) given QW for Cycles 1-3, Q3W for Cycles 4-8, and Q4W thereafter. The primary endpoint for both studies was PFS.
Results: A total of 211 (D-Vd, n=141; Vd, n=70) pts in LEPUS and 498 (D-Vd, n=251; Vd, n=247) pts in CASTOR were randomized. The median (range) age was 61 (28-82) years for Chinese and 64 (30-88) years for global pts. In general, baseline characteristics were similar between Chinese and global pts and balanced between treatment arms, with the exception of median body weight (LEPUS: 67 kg; CASTOR: 76 kg). Chinese and global pts both received a median of 2 prior lines of therapy; 79% and 66% received prior V, 27% and 28% were refractory to lenalidomide, and 64% and 32% were refractory to their last prior line of therapy, respectively.
After a median follow up of 8.2 months in LEPUS and 7.4 months in CASTOR, a consistent PFS benefit of D-Vd vs Vd was demonstrated in the pooled analysis set across age (<65, 65-74, and ≥75 years), cytogenetic risk status (standard risk and high risk), and renal function (creatinine clearance ≤60 mL/min and >60 mL/min) subgroups (Table 1). Median time to progression was also consistently prolonged with D-Vd vs Vd across pooled pt subgroups. Among response evaluable pts, D-Vd improved overall response rate, rate of very good partial response or better, and rate of complete response or better (Table 2) and prolonged median duration of response vs Vd in all pt subgroups. Additional data, including PFS2, from the pooled subgroups analysis will be presented at the meeting.
The safety profile of D-Vd was generally consistent across pts in LEPUS and CASTOR. Grade 3/4 treatment-emergent adverse events (TEAEs; D-Vd/Vd) occurring at a ≥5% frequency with D-Vd vs Vd in both Chinese and global pts included thrombocytopenia (51%/37%; 45%/33%), lymphopenia (44%/29%; 10%/3%), neutropenia (16%/6%; 13%/4%), and hypertension (12%/3%; 7%/1%). 49%/38% of Chinese and 42%/34% of global pts had ≥1 serious TEAEs. TEAEs leading to treatment discontinuation occurred in 4%/3% of Chinese and 7%/9% of global pts, and TEAEs leading to death occurred in 4%/10% of Chinese and 5%/6% of global pts. Rates of infusion-related reactions (IRRs) were similar for D-Vd across studies (LEPUS: 38%; CASTOR: 45%); most occurred during the first infusion and the majority were grade 1/2.
Conclusions: D-Vd demonstrated a clinical benefit, including significantly improved PFS, in pooled Chinese and global pts with RRMM who received ≥1 prior line of therapy, regardless of age, cytogenetic risk status, or renal function. The safety profile of D-Vd was consistent across all pts, and no new safety concerns were identified. These results support the use of D-Vd in Chinese pts with RRMM.
Disclosures: Jin: The First Affiliated Hospital of Zhejiang University: Current Employment. Spencer: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Cilag GmbH: Consultancy, Honoraria, Research Funding, Speakers Bureau. Weisel: Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Honoraria. Mateos: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nooka: Adaptive Technologies: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding. Qi: Janssen: Current Employment, Current equity holder in publicly-traded company; Johnson and Johnson: Current equity holder in publicly-traded company. Sun: Janssen: Current Employment, Current equity holder in publicly-traded company. Gai: Janssen: Current Employment, Current equity holder in publicly-traded company. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Yang: Janssen: Current Employment, Current equity holder in publicly-traded company.
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