Department of Hematology, Lille University Hospital, Lille, France
Thierry Facon , Philippe Moreau , Ivan Spicka , Kenshi Suzuki , Kwee Yong , Joseph Mikhael , Taro Fukao , Kamlesh Bisht , Nicole Armstrong , Sandrine Macé , Marie-Laure Risse , Thomas G. Martin
Background: Gain or amplification of 1q21 (1q21+, ≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma (MM), has a negative impact on prognosis due to its potential involvement in resistance to MM therapy and disease progression. In the prespecified, long-term analysis of the Phase 3 IKEMA trial in relapsed MM patients (pts), treatment with Isa-Kd showed continued, significant improvement in progression-free survival (PFS) vs Kd (HR 0.58; 95.4% CI 0.42–0.79), 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. In this subgroup analysis of IKEMA, we evaluated efficacy of Isa-Kd in pts with 1q21+ status (with or without high-risk chromosomal abnormalities [HRCA]) and related subgroups – isolated 1q21+ (≥3 copies without HRCA), gain(1q21), amp(1q21) – at long-term follow-up (44.2 months). Methods: Pts with 1–3 prior lines of therapy were randomized to Isa-Kd (n=179) or Kd (n=123). Assessment was prespecified (at 30% cut-off by FISH) for 1q21+ status as ≥3 copies, gain(1q21) as 3 copies, and amp(1q21) as ≥4 copies. Results: In the Isa-Kd and Kd arms, 41.9% and 42.3% of 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) (Table). Responses deepened by adding Isa to Kd, with increased rates of very good partial response or better (≥VGPR), ≥CR, MRD-, and MRD- ≥CR (Table). Conclusions: 1q21 abnormalities affect PFS in MM pts. Our results at long-term follow-up of pts with 1q21+ status (with or without HRCA) in the IKEMA study continue to show greater PFS benefit and deeper responses with Isa-Kd than Kd, consistent with the overall population and earlier 1q21+ subgroup interim analyses. Thus, they support Isa-Kd as an effective treatment option also for difficult-to-treat, 1q21+ pts with relapsed MM. Clinical trial information: NCT03275285.
Standard risk | 1q21+ | Isolated 1q21+ (w/o HRCA) | Gain(1q21) | Amp(1q21) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Isa-Kd | Kd | Isa-Kd | Kd | Isa-Kd | Kd | Isa-Kd | Kd | Isa-Kd | Kd | |
n | 65 | 43 | 75 | 52 | 47 | 31 | 43 | 37 | 32 | 15 |
% | 36.3 | 35.0 | 41.9 | 42.3 | 26.3 | 25.2 | 24.0 | 30.1 | 17.9 | 12.2 |
mPFS, mo (95% CI) | 42.4 (26.3–NC) | 20.3 (15.2–28.2) | 25.8 (17.1–38.2) | 16.2 (10.2–24.8) | 38.2 (18.8–NC) | 16.2 (10.2–25.1) | 30.2 (20.8–NC) | 18.2 (10.2–25.0) | 18.4 (13.1–NC) | 14.5 (2.8–NC) |
PFS HR vs Kd (95% CI) | 0.50 (0.29–0.84) | 0.58 (0.37–0.92) | 0.50 (0.27–0.92) | 0.50 (0.28–0.90) | 0.73 (0.33–1.63) | |||||
ORR % | 90.8 | 86.0 | 86.7 | 82.7 | 91.5 | 87.1 | 90.7 | 86.5 | 81.3 | 73.3 |
≥VGPR % | 76.9 | 53.5 | 73.3 | 51.9 | 80.9 | 51.6 | 79.1 | 56.8 | 65.6 | 40.0 |
MRD- % | 44.6 | 18.6 | 34.7 | 15.4 | 40.4 | 12.9 | 34.9 | 13.5 | 34.4 | 20.0 |
MRD- ≥CR % | 33.8 | 11.6 | 29.3 | 15.4 | 36.2 | 12.9 | 27.9 | 13.5 | 31.3 | 20.0 |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Jason Westin
2022 ASCO Annual Meeting
First Author: Niels W.C.J. van de Donk
2021 ASCO Annual Meeting
First Author: Nizar J. Bahlis
2023 ASCO Annual Meeting
First Author: Philipp Harter