MM-248 Long-Term Outcomes With Isatuximab-Carfilzomib-Dexamethasone (Isa-Kd) in Relapsed Multiple Myeloma (MM) Patients (pts) With 1q21+ Status: Updated Results from the Phase 3 IKEMA Study

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2023-09, Vol.23, p.S484-S485
• Main Authors: Facon, Thierry, Moreau, Philippe, Špicka, Ivan, Suzuki, Kenshi, Yong, Kwee, Mikhael, Joseph, Fukao, Taro, Bisht, Kamlesh, Armstrong, Nicole, Macé, Sandrine, Risse, Marie-Laure, Martin, Thomas
• Format: Article
• Language: English
• Subjects: 1q21; carfilzomib; dexamethasone; IKEMA; isatuximab; multiple myeloma; phase III
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/S2152-2650(23)01425-8

Gain or amplification of 1q21 (1q21+, ≥3 copies), a chromosomal abnormality frequently observed in MM, has a negative impact on prognosis due to its involvement in resistance to MM therapy and disease progression. In Phase 3 IKEMA trial (prespecified, interim analysis), in relapsed MM pts, treatment with Isa-Kd showed significant progression-free survival (PFS) improvement vs Kd (HR 0.538, 99% CI 0.318 to 0.889, one sided P=0.0007), confirmed at the time of long-term PFS analysis in which median PFS was reached for Isa-Kd (35.65 months) vs Kd (19.15 months) and with meaningful increase in depth of response (complete response or better [≥CR] 44.1% vs 28.5%; minimal residual disease negativity [MRD-] 33.5% vs 15.4%, MRD- ≥CR 26.3% vs 12.2%), and a manageable safety profile. To evaluate efficacy of Isa-Kd in pts with 1q21+ status (with or without high-risk chromosomal abnormalities [HRCA]) and related subgroups of IKEMA – isolated 1q21+ (≥3 copies without HRCA), gain(1q21), amp(1q21) – at long-term follow-up (44.2 months) (NCT03275285). Pts with 1–3 prior lines of therapy were randomized to Isa-Kd (n=179) or Kd (n=123). Assessment was prespecified (at 30% cutoff by FISH) for 1q21+ status as ≥3 copies, gain(1q21) as 3 copies, and amp(1q21) as ≥4 copies. In Isa-Kd and Kd arms, 41.9% and 42.3% pts had 1q21+ status, 26.3% and 25.2% isolated 1q21+, 24.0% and 30.1% gain(1q21), 17.9% and 12.2% amp(1q21) respectively. Greater PFS benefit was achieved with Isa-Kd vs Kd in pts with 1q21+ status (HR 0.58, 95% CI 0.37–0.92) and in pts with isolated 1q21+, gain(1q21), or amp(1q21). Responses deepened by adding Isa to Kd, with increased rates of very good partial response or better, ≥CR, MRD-, and MRD- ≥CR. 1q21 abnormalities affect PFS in MM pts. Our results at long-term follow-up of pts with 1q21+ status (with or without HRCA) in IKEMA study continue to show greater PFS benefit and deeper responses with Isa-Kd than Kd, consistent with overall population and earlier 1q21+ subgroup interim analyses. Thus, they support Isa-Kd as an effective treatment option also for difficultto-treat, 1q21+ pts with relapsed MM.