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

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.

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Correspondence to Steven Le Gouill.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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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