1q21的增益/扩增(≥3个拷贝),在多发性骨髓瘤中经常观察到的染色体异常,会对预后产生负面影响,由于其参与抗骨髓瘤治疗的耐药性和疾病进展。在这个更新的随机亚组分析中,复发性/难治性多发性骨髓瘤(RRMM)的3期IKEMA研究(NCT03275285),我们评估了抗CD38抗体异妥昔单抗加卡非佐米-地塞米松(Isa-Kd)与Kd的无进展生存期(PFS)和反应深度,在1q21+患者和相关亚组,长期随访(44.2个月)。我们的分析包括1q21+患者(≥3份,有/没有高风险染色体异常[HRCA]),隔离1q21+(≥3份,没有HRCA),增益(1q21)(3份,有/无HRCA),和amp(1q21)(≥4份,有/无HRCA)。在1q21+患者中,Isa-Kd与Kd相比实现了PFS获益(HR0.58,95%CI:0.37-0.92),与分离的1q21+(HR0.49,95%CI:0.27-0.92),随着收益(1q21),或amp(1q21),与总体人群和先前的临时1q21+亚组分析一致。在1q21+患者中,Isa-Kd和Kd的平均PFS分别为25.8和16.2个月,在1q21+患者中,平均PFS分别为38.2和16.2个月。临床上有意义,非常好的部分反应率更高或更好,完全反应或更好(≥CR),微小残留病(MRD)阴性,在1q21+患者中,Isa-Kd和Kd达到MRD阴性和≥CR,隔离1q21+,增益(1q21),或amp(1q21)。在Isa-Kd和Kd,MRD阴性和≥CR率为29.3%,1q21+患者为15.4%,36.2%与分离的1q21+患者的12.9%,增益患者的27.9%与13.5%(1q21),amp(1q21)患者的31.3%和20.0%,分别。总之,在三联疗法中添加Isa到Kd已显示出PFS益处和更深层次的反应,与Kd相比,在进展风险较高的1q21+患者中,包括孤立的1q21+患者,增益(1q21),和amp(1q21),从而支持Isa-Kd成为RRMM患者的有效治疗选择。
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.