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

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).

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Publication Details

Journal
Annals of Hematology
Published
2024-11-05
DOI
https://doi.org/10.1007/s00277-024-06076-1
Citations
2
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
0.88

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article

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

Souad Assaad, Stéphanie Poulain, Cécile Tomowiak, A. Lhermitte et al.
2 citations
Annals of Hematology
Chronic Lymphocytic Leukemia Research
0.88
article

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

Souad Assaad, Stéphanie Poulain, Cécile Tomowiak, A. Lhermitte, Charles Herbaux, Stéphane Leprêtre, Pierre Morel, Olivier Tournilhac, Sylvie Chevret, José Miguel Torregrosa Diaz, Olivier Casasnovas, Thérèse Aurran, Morgane Nudel, Damien Roos‐Weil, Bruno Villemagne, Véronique Leblond, Beatrice Mahé, Pierre Feugier
article en
2 citations

Abstract

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).

Annals of HematologyVol. 104(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Clermont Auvergne (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Université de Poitiers (FR), Sorbonne Université (FR), Lille’s Cardiology Hospital (FR), Centre Hospitalier Universitaire de Montpellier (FR), Centre Hospitalier Universitaire de Tours (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Bretonneau (FR), University of Clermont Auvergne (FR), Centre Léon Bérard (FR), Normandie Université (FR), Roche (France) (FR), Délégation Centre-Est (FR), Centre Hospitalier Universitaire de Poitiers (FR), Pitié-Salpêtrière Hospital (FR), Centre de Recherche en Économie et Statistique (FR), Maison des Sciences sociales et des Humanités de Dijon (FR), Centre Hospitalier Départemental Vendée (FR), Institut Paoli-Calmettes (FR), Laboratoire de Génétique Cellulaire (FR), Centre Henri Becquerel, Centre de Recherche Épidémiologie et Statistique (FR), Génomique du cancer et du cerveau, Université de Rouen Normandie (FR)
Gilead Sciences, Centre hospitalier régional universitaire de Lille
Zero hunger
Openalex Percentile: Top 23%
Chronic Lymphocytic Leukemia Research
0.88
DOIOpen Access PDFOpenAlex
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