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Clinical Trial
. 2025 Jan;104(1):685-690.
doi: 10.1007/s00277-024-06076-1. Epub 2024 Nov 5.

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

Cécile Tomowiak  1   2 , Stéphanie Poulain  3   4 , Morgane Nudel  5 , Pierre Feugier  6 , Charles Herbaux  7 , Béatrice Mahé  8 , Pierre Morel  9 , Thérèse Aurran  10 , Olivier Tournilhac  11 , Stéphane Leprêtre  12 , Souad Assaad  13 , Bruno Villemagne  14 , Olivier Casasnovas  15 , Adeline Lhermitte  16 , Damien Roos-Weil  17 , José Torregrosa-Diaz  18 , Sylvie Chevret  19 , Véronique Leblond  17 ; on the behalf of the FILO group
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Clinical Trial

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

Cécile Tomowiak et al. Ann Hematol. 2025 Jan.

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).

Keywords: Idélalisib; Obinutuzumab; Relapse/refractroy; Waldenstrom magroglobulinemia.

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Conflict of interest statement

Declarations. Ethical approval: This study is in accordance with the principles laid down by the 18th World Medical Assembly (Helsinki, 1964) and amendments laid down by the 29th (Tokyo, 1975), the 35th (Venice, 1983) and the 41st (Hong Kong, 1989), the 48th (Somerset West, 1996), the 52nd ( Edinburg, 2000) World Medical Assemblies, the 64th (Fortazela, 2013) notes for clarification added by the WMA General Assembly on paragraph 29 (Washington 2002) and on Paragraph 30 (Tokyo 2004) and amendment laid down by the 59th (Seoul, October 2008) World Medical Assemblies. The trial was approved by the following competent authorities: health autority (ANSM) autorisation date: August 25, 2016 and ethics comittee (CPP OUEST III): August 31, 2016. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Impact of CXCR4 (a, b) and TP53 (c, d) mutations on survival rates. Blue line: presence of mutation (MUT), red line: absence of mutation (WT). PFS: progression-free survival, OS: overall survival
Fig. 2
Fig. 2
Progression-free survival after relapse (PFS2). PFS: progression-free survival, vs: versus
See this image and copyright information in PMC

References

    1. Garcia-Sanz R, Varettoni M, Jiménez C, Ferrero S, Poulain S, San-Miguel JF, Guerrera ML, Drandi D, Bagratuni T, McMaster M, Roccaro AM, Roos-Weil D, Leiba M, Li Y, Qiu L, Hou J, De Larrea CF, Castillo JJ, Dimopoulos M, Owen RG, Treon SP, Hunter ZR (2023) Report of Consensus Panel 3 from the 11th International workshop on Waldenström’s Macroglobulinemia: Recommendations for molecular diagnosis in Waldenström’s Macroglobulinemia. Semin Hematol 60(2):90–96 - PubMed
    1. Castillo JJ, Advani RH, Branagan AR, Buske C, Dimopoulos MA, D’Sa S et al (2020) Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol 7(11):e827–e837 - PubMed
    1. Castillo JJ, Allan JN, Siddiqi T, Advani RH, Meid K, Leventoff C et al (2022) Venetoclax in Previously Treated Waldenström Macroglobulinemia. J Clin Oncol 40(1):63–71 - PMC - PubMed
    1. Treon SP, Meid K, Hunter ZR, Flynn CA, Sarosiek SR, Leventoff CR et al (2021) Phase 1 study of ibrutinib and the CXCR4 antagonist ulocuplumab in CXCR4-mutated Waldenstrom macroglobulinemia. Blood 138(17):1535–1539 - PMC - PubMed
    1. Treon SP, Buske C, Thomas SK, Castillo JJ, Branagan AR, Dimopoulos MA et al (2021) Preliminary clinical response data from a phase 1b study of mavorixafor in combination with ibrutinib in patients with Waldenstrom’s acroglobulinemia with MYD88 and CXCR4 mutations. Blood 138(Supplement 1):1362

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