Touzeau Cyrille, Leleu Xavier, Tiab Mourad, Macro Margaret, Perrot Aurore, Gay Julie, Chateleix Carine, Moreau Stéphane, Karlin Lionel, Jacquet Caroline, Manier Salomon, Hulin Cyrille, Decaux Olivier, Richez Valentine, Chalopin Thomas, Mohty Mohamad, Orsini-Piocelle Frédérique, Caillot Denis, Sonntag Cécile, Vignon Marguerite, Bobin Arthur, Avet-Loiseau Hervé, Jobert Alexandra, Planche Lucie, Corre Jill, Moreau Philippe
Service d'hématologie, Centre Hospitalo-Universitaire, Nantes, France.
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
Br J Haematol. 2025 May;206(5):1366-1372. doi: 10.1111/bjh.19978. Epub 2025 Jan 5.
Most transplant-ineligible patients present with multiple myeloma (MM) refractory to lenalidomide and/or anti-CD38 monoclonal antibody at first relapse and represent a difficult-to-treat population. The Intergroupe Francophone du Myélome phase 2 study iberdomide, ixazomib and dexamethasone (I2D) evaluated the oral triplet iberdomide, ixazomib and dexamethasone in MM patients aged ≥70 years at first relapse (NCT04998786). Seventy patients were enrolled to receive iberdomide (1.6 mg on day 1-21), ixazomib (3 mg on day 1, 8, 15) and dexamethasone (20 mg on day 1, 8, 15, 22 on cycle 1-2 and 10 mg on day 1, 8, 15, 22 on cycle 3-6) (28-day cycle) until disease progression. Median age was 76; 50% patients were frail according to the International Myeloma Working Group frailty score; 74% and 37% were refractory to lenalidomide and daratumumab respectively. With a median follow-up of 14 months, the overall response rate was 64%, including 36% very good partial response or better. The 12-month progression-free survival, duration of response and overall survival were 52%, 76% and 86% respectively. The most common (46%) grade 3-4 toxicity was neutropenia. Non-haematological adverse events were mostly grade 1 or 2. Overall, I2D demonstrated a favourable risk-benefit profile in elderly MM patients at first relapse, including in patients with lenalidomide and daratumumab refractory disease.
大多数不符合移植条件的患者在首次复发时表现为对来那度胺和/或抗CD38单克隆抗体难治的多发性骨髓瘤（MM），代表了一个难以治疗的群体。法语国家骨髓瘤研究组的2期研究iberdomide、伊沙佐米和地塞米松（I2D）评估了口服三联疗法iberdomide、伊沙佐米和地塞米松在≥70岁首次复发的MM患者中的疗效（NCT04998786）。70名患者入组接受iberdomide（第1 - 21天1.6毫克）、伊沙佐米（第1、8、15天3毫克）和地塞米松（第1、8、15、22天20毫克，第1 - 2周期；第1、8、15、22天10毫克，第3 - 6周期）（28天周期），直至疾病进展。中位年龄为76岁；根据国际骨髓瘤工作组虚弱评分，50%的患者虚弱；分别有74%和37%的患者对来那度胺和达雷妥尤单抗难治。中位随访14个月，总缓解率为64%，包括36%的非常好的部分缓解或更好。12个月的无进展生存期、缓解持续时间和总生存期分别为52%、76%和86%。最常见的（46%）3 - 4级毒性是中性粒细胞减少。非血液学不良事件大多为1级或2级。总体而言，I2D在老年MM首次复发患者中显示出良好的风险效益比，包括对来那度胺和达雷妥尤单抗难治的疾病患者。
