Department of Hematology, Lille University Hospital, Lille, France.
Department of Hematology, University Hospital Hôtel-Dieu, Nantes, France.
Hematol Oncol. 2024 Mar;42(2):e3258. doi: 10.1002/hon.3258.
Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months). Our analysis included patients with 1q21+ (≥3 copies, with/without high-risk chromosomal abnormality [HRCA]), isolated 1q21+ (≥3 copies, without HRCA), gain(1q21) (3 copies, with/without HRCA), and amp(1q21) (≥4 copies, with/without HRCA). PFS benefit was achieved with Isa-Kd versus Kd in patients with 1q21+ (HR 0.58, 95% CI: 0.37-0.92), with isolated 1q21+ (HR 0.49, 95% CI: 0.27-0.92), with gain(1q21), or amp(1q21), consistent with the overall population and prior interim 1q21+ subgroup analyses. Median PFS with Isa-Kd versus Kd was 25.8 versus 16.2 months in 1q21+ patients and 38.2 versus 16.2 months in patients with isolated 1q21+. Clinically meaningful, higher rates of very good partial response or better, complete response or better (≥CR), minimal residual disease (MRD) negativity, and MRD negativity and ≥CR were reached with Isa-Kd versus Kd in patients with 1q21+, isolated 1q21+, gain(1q21), or amp(1q21). In Isa-Kd and Kd, the MRD negativity and ≥CR rate was 29.3% versus 15.4% in 1q21+ patients, 36.2% versus 12.9% in patients with isolated 1q21+, 27.9% versus 13.5% in patients with gain(1q21), and 31.3% versus 20.0% in patients with amp(1q21), respectively. In conclusion, addition of Isa to Kd in triplet combination therapy has shown PFS benefit and deeper responses, compared with Kd, in 1q21+ patients at higher risk of progression, including patients with isolated 1q21+, gain(1q21), and amp(1q21), thus supporting Isa-Kd an effective treatment option for patients with RRMM.
1q21 获得/扩增（≥3 个拷贝）是多发性骨髓瘤中经常观察到的染色体异常，可能会对预后产生负面影响，因为它与抗骨髓瘤治疗耐药和疾病进展有关。在这项复发/难治性多发性骨髓瘤（RRMM）的随机、3 期 IKEMA 研究（NCT03275285）的更新亚组分析中，我们评估了在长期随访（44.2 个月）中，抗 CD38 抗体 isatuximab 联合 carfilzomib-地塞米松（Isa-Kd）与 Kd 相比，在 1q21+患者和相关亚组中，无进展生存期（PFS）和反应深度。我们的分析包括 1q21+（≥3 个拷贝，有/无高危染色体异常[HRCA]）、孤立的 1q21+（≥3 个拷贝，无 HRCA）、增益（1q21）（3 个拷贝，有/无 HRCA）和扩增（1q21）（≥4 个拷贝，有/无 HRCA）患者。与 Kd 相比，Isa-Kd 在 1q21+患者（HR 0.58，95%CI：0.37-0.92）、孤立的 1q21+患者（HR 0.49，95%CI：0.27-0.92）、增益（1q21）或扩增（1q21）中达到了 PFS 获益，与总体人群和先前的 1q21+亚组分析一致。与 Kd 相比，Isa-Kd 治疗的 1q21+患者的中位 PFS 为 25.8 个月 vs. 16.2 个月，孤立的 1q21+患者为 38.2 个月 vs. 16.2 个月。与 Kd 相比，1q21+、孤立的 1q21+、增益（1q21）或扩增（1q21）患者接受 Isa-Kd 治疗后，获得了更高比例的非常好的部分缓解或更好、完全缓解或更好（≥CR）、微小残留病（MRD）阴性和 MRD 阴性和≥CR。在 Isa-Kd 和 Kd 中，1q21+患者的 MRD 阴性和≥CR 率分别为 29.3% vs. 15.4%，孤立的 1q21+患者为 36.2% vs. 12.9%，增益（1q21）患者为 27.9% vs. 13.5%，扩增（1q21）患者为 31.3% vs. 20.0%。总之，与 Kd 相比，在风险更高的进展患者中，包括孤立的 1q21+、增益（1q21）和扩增（1q21）患者，三重组合疗法中添加 Isa 至 Kd 可提高 PFS 并增加反应深度，支持 Isa-Kd 作为 RRMM 患者的有效治疗选择。
