Six-year follow-up of phase II study exploring chemo-free treatment association with idelalisib and obinutuzumab in symptomatic relapsed/ refractory patients with Waldenström's macroglobulinemia

被引：1

作者：

Tomowiak, Cecile ^{[1
,2
,23
,24
]}

Poulain, Stephanie ^{[3
,4
]}

Nudel, Morgane ^{[5
]}

Feugier, Pierre ^{[6
]}

Herbaux, Charles ^{[7
]}

Mahe, Beatrice ^{[8
]}

Morel, Pierre ^{[9
]}

Aurran, Therese ^{[10
]}

Tournilhac, Olivier ^{[11
,12
]}

Lepretre, Stephane ^{[13
,14
,15
]}

Assaad, Souad ^{[16
]}

Villemagne, Bruno ^{[17
]}

Casasnovas, Olivier ^{[18
,19
]}

Lhermitte, Adeline ^{[20
]}

Roos-Weil, Damien ^{[21
]}

Torregrosa-Diaz, Jose ^{[1
,2
]}

Chevret, Sylvie ^{[22
]}

Leblond, Veronique ^{[21
]}

机构：

[1] Univ Hosp, Hematol Dept, Poitiers, France

[2] Univ Hosp, INSERM CIC1402, Poitiers, France

[3] Univ Lille, INSERM 1277 CNRS 9020 UMRS 12, Lille, France

[4] CHU Lille, Biol & Pathol Ctr, Lab Hematol, F-59000 Lille, France

[5] Lille Univ Hosp, Dept Cardiac Surg, Lille, France

[6] Univ Hosp, Dept Hematol, Vandoeuvre Les Nancy, France

[7] Montpellier Univ Hosp, Pediat Oncol Dept, Montpellier, France

[8] Univ Hosp, Hematol Dept, Nantes, France

[9] Univ Hosp Amiens Picardie, Dept Gerontol, F-80054 Amiens, Picardie, France

[10] Inst Paoli Calmettes, Dept Hematol, Marseille, France

[11] Univ Clermont Auvergne, Univ Hosp Estaing, Hematol Dept, EA 7453, Clermont Ferrand, France

[12] CIC1405, Clermont Ferrand, France

[13] Ctr Henri Becquerel, Inserm U1245, Rouen, France

[14] Ctr Henri Becquerel, Dept Hematol, Rouen, France

[15] Normandie Univ UNIROUEN, Rouen, France

[16] Ctr Leon Berard, Lyon, France

[17] CHD, Hematol Dept, F-85025 La Roche Sur Yon, France

[18] Univ Hosp Dijon Bourgogne, Dept Hematol, Dijon, France

[19] INSERM1231, Dijon, France

[20] Bretonneau Univ Hosp, Hematol Lab, 2 Bld Tonnelle, F-37044 Tours, France

[21] Sorbonne Univ, Hop Pitie Salpetriere APHP, Dept Hematol, Paris, France

[22] Ctr Univ Paris, Equipe Rech Biostatist & Epidemiol Clin ECSTRRA, Paris, France

[23] Hop La Miletrie, Fac Med, Serv Hematol &Therapie Cellulaire, PRC, 2 Rue La Miletrie, F-86021 Poitiers, France

[24] CHU, Inserm CIC 1402, 2 Rue La Miletrie, F-86021 Poitiers, France

来源：

ANNALS OF HEMATOLOGY | 2025年 / 104卷 / 01期

关键词：

Waldenstrom magroglobulinemia; Relapse/refractroy; Obinutuzumab; Id & eacute; lalisib; WALDENSTROM MACROGLOBULINEMIA; IBRUTINIB; ZANUBRUTINIB; MONOTHERAPY;

D O I：

10.1007/s00277-024-06076-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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).

引用

页码：685 / 690

页数：6