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Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP)

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Abstract

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.

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Acknowledgments

The authors would like to thank A. La Torre, M. Lecciso, C. Plati, and F. Clemente who contributed to the collection of clinical data; medical doctors of REP and nurses; and all the patients, families, caregivers, and AIL staff who contributed to this study.

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Authors and Affiliations

  1. Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, Via San Pio X, 73039, Tricase (LE), Italy

    Anna Mele, Eleonora Prete, Clara De Risi, Stefania Citiso, Giuseppina Greco, Antonino Greco, Rosa De Francesco, Silvia Sibilla, Lorenzo Tonialini, Maria Rosaria Morciano & Vincenzo Pavone

  2. Department of Hematology and Bone Marrow Transplant, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Antonietta Pia Falcone, Grazia Sanpaolo & Nicola Cascavilla

  3. Department of Hematology, Hospital Perrino, Brindisi, Italy

    Giuseppe Mele, Angela Giannotta & Domenico Pastore

  4. Department of Hematology, Hospital Vito Fazzi, Lecce, Italy

    Carolina Vergine, Giovanni Reddiconto & Nicola Di Renzo

  5. Department of Hematology and Bone Marrow Transplant, Hospital G.Moscati, Taranto, Italy

    Giulia Palazzo, Sabrina Sabatelli & Patrizio Mazza

  6. Department of Hematology, ASL BT, Barletta, Italy

    Candida Germano, Rosanna Miccolis & Giuseppe Tarantini

  7. Department of Hematology and Bone Marrow Transplant, Policlinico, University of Bari, Bari, Italy

    Paola Curci, Rita Rizzi & Giorgina Specchia

  8. Department of Hematology, Hospital University Riuniti, Foggia, Italy

    Gaetano Palumbo & Silvana Capalbo

  9. Department of Hematology and Bone Marrow Transplant, Osp Riuniti Ancona, University of Ancona, Ancona, Italy

    Massimo Offidani

  10. Department of Hematology, Hospital IRCCS Oncologico, Bari, Italy

    Attilio Guarini

Authors
  1. Anna Mele
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  2. Eleonora Prete
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  12. Giulia Palazzo
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  14. Candida Germano
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  15. Rosanna Miccolis
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  16. Paola Curci
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  17. Gaetano Palumbo
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  19. Rita Rizzi
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  21. Domenico Pastore
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  28. Antonino Greco
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  29. Rosa De Francesco
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  30. Silvia Sibilla
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  31. Lorenzo Tonialini
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  32. Maria Rosaria Morciano
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  33. Vincenzo Pavone
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Correspondence to Anna Mele.

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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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Mele, A., Prete, E., De Risi, C. et al. Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP). Ann Hematol 100, 429–436 (2021). https://doi.org/10.1007/s00277-020-04329-3

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