Safety and efficacy of temsirolimus in combination with three different immuno-chemotherapy regimens in relapse and refractory mantle cell lymphoma, final results of the T3 phase IB trial of the LYSA

Annals of Hematology volume 99, pages1771–1778(2020)Cite this article

Abstract

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1–3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.

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Acknowledgements

• KB, BB, TL, RG, GC, CT, CS, CH, OC, EG, OH, and SLG performed the research.

• SLG designed the research study.

• BT and SLG analyzed the data and wrote the paper.

• CJ performed the statistical analyses.

Funding

This trial was funded by Pfizer, Inc. and LYSARC was the sponsor.

Author information

Affiliations

  1. Department of Hematology, CHU de Nantes, University Hospital of Nantes, Nantes, France

    Benoît Tessoulin & Steven Le Gouill

  2. INSERM, UMR892, Equipe 10, Nantes, France

    Benoît Tessoulin & Steven Le Gouill

  3. Haematology, CHU de Bordeaux, Bordeaux, France

    Kamal Bouabdallah

  4. Pathology Department, Cochin University Hospital, AP-HP, Paris, France

    Barbara Burroni

  5. INSERM U917, CHU Pontchaillou, Rennes, France

    Thierry Lamy

  6. Hematology, CHU Grenoble, Grenoble, Grenoble, France

    Remy Gressin

  7. Department of clinical hematology, University Hospital Montpellier, Montpellier, France

    Guillaume Cartron

  8. Hôpital Saint-Louis, Paris, France

    Catherine Thieblemont

  9. Hematology, Hospices Civils de Lyon, Pierre Bénite, Lyon, France

    Clémentine Sarkozy

  10. Lymphoid Malignancies Unit, AP-HP, Groupe Hospitalier Mondor, Croéteil, France

    Corinne Haioun

  11. Hematology Department, Hopital Le Bocage, CHU Dijon, Dijon, France

    Olivier Casasnovas

  12. Department of Biostatistics, LYSARC, Lyon, France

    Clementine Joubert

  13. Service d′Hématologie et thérapie cellulaire, Centre Hospitalier Universitaire, Tours, France

    Emmanuel Gyan

  14. Hematology Department, Necker University Hospital, AP-HP, Paris, France

    Olivier Hermine

  15. INSERM, CIC 004, Nantes University Hospital, Nantes, France

    Steven Le Gouill

Authors
  1. Benoît Tessoulin
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  2. Kamal Bouabdallah
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  3. Barbara Burroni
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  7. Catherine Thieblemont
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  8. Clémentine Sarkozy
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  10. Olivier Casasnovas
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  11. Clementine Joubert
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  12. Emmanuel Gyan
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  13. Olivier Hermine
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  14. Steven Le Gouill
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Correspondence to Steven Le Gouill.

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Tessoulin, B., Bouabdallah, K., Burroni, B. et al. Safety and efficacy of temsirolimus in combination with three different immuno-chemotherapy regimens in relapse and refractory mantle cell lymphoma, final results of the T3 phase IB trial of the LYSA. Ann Hematol 99, 1771–1778 (2020). https://doi.org/10.1007/s00277-020-04159-3

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Keywords

  • Mantle cell lymphoma
  • Temsirolimus
  • Immuno-chemotherapy