Tomowiak Cécile, Poulain Stéphanie, Nudel Morgane, Feugier Pierre, Herbaux Charles, Mahé Béatrice, Morel Pierre, Aurran Thérèse, Tournilhac Olivier, Leprêtre Stéphane, Assaad Souad, Villemagne Bruno, Casasnovas Olivier, Lhermitte Adeline, Roos-Weil Damien, Torregrosa-Diaz José, Chevret Sylvie, Leblond Véronique
Hematology Department and CIC1402 INSERM, University Hospital, Poitiers, France.
Service d'Hématologie Et Thérapie Cellulaire, PRC, Hôpital de La Milétrie, Faculté de Médecine And Inserm CIC 1402, CHU, 2 Rue de La Milétrie, 86021, Poitiers Cedex, France.
Ann Hematol. 2025 Jan;104(1):685-690. doi: 10.1007/s00277-024-06076-1. Epub 2024 Nov 5.
We present the 6-year update of a phase 2 study evaluating the combination of obinutuzumab and idelalisib in relapse/refractory Waldenstrom macroglobulinemia. The results of the REMODEL trial demonstrated interesting efficacy in a high-risk genotype profile population. The primary endpoint was achieved with a median PFS of 25.4 months (95% CI, 15.7 to 29.0). However, a major limitation of idelalisib is its toxicity. With a median follow-up of 70.9 months, median OS was still not reached, and 5-year OS was 72.9% (95% CI, 61.3 to 86.6). We confirm that CXCR4 mutations had no impact on PFS or OS. However, TP53 mutated patients had shorter OS. At the time of analysis, six patients are alive without relapse and 40 had progressive disease. Among the 38 patients who received a new treatment, the median time to second progression was not reached in ibrutinib treated patients (n = 17) versus 30.8 months in patients treated with other options (95% CI, 16.9 to NA), p = 0.005. With longer follow-up our prospective study is the first to show an impact of TP53 mutations in patients treated with fixed duration chemo-free regimen leading to a significant shorter OS in this population. Moreover, ibrutinib remains an effective treatment after this combination. This study was registered on the clinicaltrial.gov web (NCT02962401, November 9, 2016).
我们展示了一项2期研究的6年更新结果，该研究评估了奥妥珠单抗和idelalisib联合用于复发/难治性华氏巨球蛋白血症的疗效。REMODEL试验的结果在高风险基因型谱人群中显示出有趣的疗效。主要终点得以实现，中位无进展生存期（PFS）为25.4个月（95%置信区间，15.7至29.0）。然而，idelalisib的一个主要局限性是其毒性。中位随访70.9个月时，中位总生存期（OS）仍未达到，5年总生存率为72.9%（95%置信区间，61.3至86.6）。我们证实CXCR4突变对PFS或OS没有影响。然而，TP53突变的患者总生存期较短。在分析时，6例患者存活且未复发，40例患者病情进展。在接受新治疗的38例患者中，接受伊布替尼治疗的患者（n = 17）未达到第二次进展的中位时间，而接受其他治疗方案的患者为30.8个月（95%置信区间，16.9至无可用数据），p = 0.005。随着随访时间延长，我们的前瞻性研究首次表明TP53突变对接受固定疗程无化疗方案治疗的患者有影响，导致该人群的总生存期显著缩短。此外，在这种联合治疗后，伊布替尼仍然是一种有效的治疗方法。本研究已在clinicaltrial.gov网站注册（NCT02962401，2016年11月9日）。
