Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis
Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis
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DOI：
10.1016/j.leukres.2021.106576
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发表时间：
2021-04-08
影响因子：
2.7
通讯作者：
Richardson, Paul G.
中科院分区：
文献类型：
--
作者：
Bringhen, Sara;Pour, Ludek;Richardson, Paul G.
复发性/难治性多发性骨髓瘤（RRMM）患者会经历多次复发，并且对连续治疗变得难治。在ICARIA-MM试验（NCT 02990338）中，isatuximab联合泊马度胺-地塞米松延长了RRMM患者的中位无进展生存期（PFS）。ICARIA-MM的亚组分析根据既往治疗线和难治性状态评估了isatuximab的治疗获益。共有307例患者随机分配至isatuximab-pomalidomide-地塞米松组（n = 154）或pomalidomide-地塞米松组（n = 153）。在第一个28天周期中每周一次给予Isatuximab（10 mg/kg静脉给药），然后每隔一周给药一次。给予标准泊马度胺-地塞米松剂量。根据既往线和难治性状态评估PFS。总体而言，102例（66%）接受isatuximab-pomalidomide-地塞米松治疗的患者和101例（66%）接受pomalidomide-地塞米松治疗的患者接受了2？3条既往线;分别有52例（34%）和52例（34%）接受过>3条既往线。对于接受2？既往接受过3种治疗（12.3 vs 7.8个月）和>3种既往治疗（9.4 vs 4.3个月）。在来那度胺难治性（11.4 vs. 5.6个月）、来那度胺末线治疗难治性（11.6 vs. 5.7个月）、蛋白酶体抑制剂（PI）难治性（11.4 vs. 5.6个月）和双重难治性（11.2 vs. 4.8个月）患者中，isatuximab-pomalidomide-地塞米松组的中位PFS高于pomalidomide-地塞米松组。在来那度胺难治性患者中，接受isatuximab-泊马度胺-地塞米松与泊马度胺-地塞米松治疗的患者的总缓解率（ORR）分别为59.0%与31.4%;在PI难治性患者中分别为60.2%与32.2%;在双重难治性患者中分别为58.6%与29.9%。无论既往治疗线或难治性状态如何，Isatuximab-pomalidomide-地塞米松均可改善PFS和ORR，与总体人群中的获益一致。
Patients with relapsed/refractory multiple myeloma (RRMM) experience several relapses, and become refractory to successive therapies. In the ICARIA-MM trial (NCT02990338), isatuximab plus pomalidomide-dexamethasone prolonged median progression-free survival (PFS) in patients with RRMM. This subgroup analysis of ICARIA-MM assessed the treatment benefit of isatuximab by prior lines of therapy and refractory status. A total of 307 patients were randomized to isatuximab-pomalidomide-dexamethasone (n = 154) or pomalidomide-dexamethasone (n = 153). Isatuximab (10 mg/kg intravenously) was given weekly in the first 28-day cycle, then every other week. Standard pomalidomide-dexamethasone doses were given. PFS was assessed by prior lines and refractory status. Overall, 102 (66 %) patients receiving isatuximab-pomalidomide-dexamethasone and 101 (66 %) patients receiving pomalidomidedexamethasone had received 2?3 prior lines; 52 (34 %) and 52 (34 %) had received >3 prior lines, respectively. Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who received 2?3 prior lines of therapy (12.3 vs. 7.8 months) and >3 prior lines of therapy (9.4 vs. 4.3 months). Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who were lenalidomide-refractory (11.4 vs. 5.6 months), lenalidomide-refractory at last line (11.6 vs. 5.7 months), refractory to a proteasome inhibitor (PI) (11.4 vs. 5.6 months), and double-refractory (11.2 vs. 4.8 months). Overall response rate (ORR) in patients receiving isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone was 59.0 % versus 31.4 % in lenalidomide-refractory; 60.2 % versus 32.2 % in PI-refractory; and 58.6 % versus 29.9 % in doublerefractory patients. Isatuximab-pomalidomide-dexamethasone improved PFS and ORR regardless of prior lines of therapy or refractory status, consistent with the benefit in the overall population.