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Front-line fludarabine-cyclophosphamide-rituximab (FCR) in 110 patients with chronic lymphocytic leukaemia (CLL): real-life experience with long-term outcomes, toxicities and responses to second-line therapies

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Abstract

Fludarabine-cyclophosphamide-rituximab (FCR) has been the gold standard front-line treatment for fit CLL patients until novel agent’s introduction. Decision between either time-limited FCR or “endless” Bruton’s tyrosine kinase inhibitor (BTKi) therapy may be difficult in fit IGHV-mutated-non-TP53 cases. We describe the outcomes after front-line FCR in 110 CLL patients from 5 centres in Catalonia, Spain, over a period of more than 10 years. ORR was 96.3% and CR 74.5%. Median second-treatment free survival (TFS1) was 6.2 years and median OS was 10.8 years. 50 (45.5%) patients required a subsequent therapy. Median third-treatment free survival was better for BTKi than for chemotherapy ± antiCD20 strategies (not reached vs 3.1 years, p = 0.003). Only 50 (45.5%) patients completed 6 cycles of FCR, and the main reason for discontinuation was cytopenia 29 (26.4%). 15 (13.6%) patients developed a second cancer, and 5 (4.5%) patients experienced a Richter's transformation (RT). At the end of follow-up, 50 (45.5%) patients remained in CR. Response rates, TFS1, OS, RT, and second cancers did not differ between patients treated with 6 vs 4 cycles of FCR. In conclusion, front-line FCR treatment leads to very long CR in almost half of patients, and BTKi yields excellent outcomes in relapsed patients.

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Authors and Affiliations

  1. Department of Clinical Hematology, Catalan Institute of Oncology (ICO)-Hospital Duran i Reynals, IDIBELL, Gran Vía 199-203, Hospitalet, 08908, Barcelona, Spain

    Ana C. Oliveira, Eva Domingo-Domenech, Patricia López, Anna Sureda & Eva González-Barca

  2. Department of Clinical Hematology, ICO-Hospital Josep Trueta, Girona, Spain

    Josep Maria Roncero & David Gallardo

  3. Department of Clinical Hematology, ICO-Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    Christelle Ferrá & Josep Maria Ribera

  4. Department of Clinical Hematology, ICO-Hospital Joan XXIII, Tarragona, Spain

    Janilson Do Nascimento & Josep Sarrá

  5. Department of Clinical Hematology, ICO-Hospital Verge de la Cinta, Tortosa, Tarragona, Spain

    Marta Rodriguez-Luaces

  6. Clinical Research Unit, ICO-Hospital Duran i Reynals, IDIBELL, Hospitalet, Barcelona, Spain

    Maite Encuentra

Authors
  1. Ana C. Oliveira
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Contributions

ACO: Honoraria for consultancy from Janssen-Cilag, Abbvie, Alexion; for speaker from Janssen-Cilag, Abbvie, AstraZeneca, Alexion, Takeda, Roche and for travel from Janssen-Cilag, Abbvie, Alexion. JMR: Honoraria for consultancy from Janssen-Cilag; for speaker from Abbvie, Janssen-Cilag, AstraZeneca, Roche, Gilead and for travel from Abbvie, Janssen-Cilag, Roche. CF: Honoraria for speaker from Abbvie, AstraZeneca, Janssen. MR-L: Honoraria for travel from Janssen-Cilag. ED-D: Honoraria for consultancy from Takeda, Roche; for speaker from Takeda and for travel from BMS-Cellgene, Roche. AS: Honoraria for consultancy from MSD, Roche, Janssen, Astra Zeneca Takeda, Pierre Fabre, GenMab, BMS Celgene, Kite, Novartis, Janssen, Sanofi and for speaker from Pierre Fabre, Takeda, MSD, BMS/Celgene, Novartis, Gilead Kite, Sanofi, GenMab. EG-B: Honoraria for consultancy from Janssen-Cilag, Abbvie, Gilead, Kiowa, EUSAPharma, Incyte, Lilly, Beigene, Novartis; for speaker from Janssen-Cilag, Abbvie, Takeda, Roche, EUSAPharma, Incyte and for travel from Janssen-Cilag, Abbvie, Roche, EUSAPharma.

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Correspondence to Ana C. Oliveira.

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Competing interests

Janilson Do Nascimento, David Gallardo, Maite Encuentra, Patricia López, Josep Maria Ribera and Josep Sarrá declare that they have no conflicts of interest.

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Oliveira, A.C., Roncero, J.M., Ferrá, C. et al. Front-line fludarabine-cyclophosphamide-rituximab (FCR) in 110 patients with chronic lymphocytic leukaemia (CLL): real-life experience with long-term outcomes, toxicities and responses to second-line therapies. Int J Hematol 117, 388–397 (2023). https://doi.org/10.1007/s12185-022-03488-5

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  • DOI: https://doi.org/10.1007/s12185-022-03488-5

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