Isatuximab plus carfilzomib and dexamethasone in east Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis.

person Kihyun Kim Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea info_outline Kihyun Kim, Chang Ki Min, Youngil Koh, Kenichi Ishizawa, Sung-Hyun Kim, Shigeki Ito, Tanaka Junji, Michihiro Uchiyama, Yawara Kawano, Jin Seok Kim, Philippe Moreau, Thomas G. Martin, Yvonne Dong, Marie-Laure Risse, Kenshi Suzuki

Authors person Kihyun Kim Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea info_outline Kihyun Kim, Chang Ki Min, Youngil Koh, Kenichi Ishizawa, Sung-Hyun Kim, Shigeki Ito, Tanaka Junji, Michihiro Uchiyama, Yawara Kawano, Jin Seok Kim, Philippe Moreau, Thomas G. Martin, Yvonne Dong, Marie-Laure Risse, Kenshi Suzuki Organizations Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea, Seoul National University Hospital, Seoul, South Korea, Department of Hematology and Cell Therapy, Yamagata University, Yamagata, Japan, Department of Internal Medicine, Dong-A University Medical Center, Busan, South Korea, Division of Hematology & Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan, Department of Hematology, Tokyo Women's Medical University, Tokyo, Japan, Department of Hematology, Japanese Red Cross Society, Suwa Hospital, Suwa, Japan, Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan, Department of Hematology, Severance Hospital, Seoul, South Korea, Hematology, University Hospital Hotel-Dieu, Nantes, France, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Sanofi Research & Development, Beijing, China, Sanofi R&D, Vitry-Alfortville, France, Japanese Red Cross Medical Center, Myeloma/Amyloidosis Center, Tokyo, Japan Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Sanofi Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P = 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m 2 days 1-2, 56 mg/m 2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285 East Asia ITT Isa-Kd n = 25 Kd n = 21 Isa-Kd n = 179 Kd n = 123 PFS HR 0.638 (95% CI: 0.231-1.764) 0.531 (99% CI:0.318–0.889) ≥VGPR rate, n (%) 20 (80.0) 11 (52.4) 130 (72.6) 69 (56.9) CR rate, n (%) 11 (44.0) 5 (23.8) 71 (39.7) 34 (27.6) MRD– rate, n (%) 11 (44.0) 2 (9.5) 53 (29.6) 16 (13.0) ≥Grade 3 TEAE, n (%) 19 (79.2)* 11 (55.0)** 136 (76.8) † 82 (67.2) †† Serious TEAE, n (%) 11 (45.8)* 10 (50.0)** 105 (59.3) † 70 (57.4) †† Fatal TEAE, n (%) 0* 1 (5.0)** 6 (3.4) † 4 (3.3) †† *n = 24, **n = 20, † n = 177, †† n = 122.