Advertisement

Pomalidomide, cyclophosphamide, and dexamethasone for relapsed/refractory multiple myeloma patients in a real-life setting: a single-center retrospective study

  • Sabrina Trudel
  • Benoît Tessoulin
  • Maxime Jullien
  • Nicolas Blin
  • Thomas Gastinne
  • Béatrice Mahé
  • Viviane Dubruille
  • Antoine Bonnet
  • Anne Lok
  • Patrice Chevallier
  • Pierre Peterlin
  • Alice Garnier
  • Thierry Guillaume
  • Amandine Le Bourgeois
  • Steven Le Gouill
  • Philippe Moreau
  • Cyrille TouzeauEmail author
Original Article
  • 14 Downloads

Abstract

Pomalidomide dexamethasone is a standard of care for relapsed multiple myeloma (MM) patients who received at least two prior lines of therapy, including both lenalidomide and proteasome inhibitors (PI). We report here a real-life single-center series of 49 consecutive patients with relapsed and refractory MM treated with the triplet pomalidomide cyclophosphamide dexamethasone (PCD) combination. The median of prior lines of therapy was 3 and all patients were previously exposed to proteasome inhibitors and lenalidomide. The overall response rate was 76%, including 27% very good partial response or better. With a median follow-up of 16 months, the median progression-free survival (PFS) was 7.3 months and the median overall survival was not reached. Regarding safety, most frequent toxicity was hematologic, including 37% grade 3–4 cytopenias. Nine patients (18%) discontinued therapy due to adverse event. Our study confirms that PCD combination is feasible and results in favorable response rate and PFS in comparison with pomalidomide dexamethasone alone.

Keywords

Multiple myelomas Pomalidomide Cyclophosphamide Dexamethasone Relapse PCD 

Notes

Acknowledgements

CT, PM, and SLG are members of Site de Recherche Intégrée sur le Cancer (SIRIC) « ILIAD » (INCA-DGOS-Inserm_12558).

Authorship

CT, PM, and ST designed the study. ST collected the data. ST and BT performed statistical analysis. CT and ST wrote the manuscript. All authors treated patients and critically reviewed the manuscript and gave the final approval.

Compliance with ethical standards

Conflict of interest

CT and PM are advisory board member and received honoraria from Celgene.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111:2516–2520.  https://doi.org/10.1182/blood-2007-10-116129 CrossRefGoogle Scholar
  2. 2.
    Kumar SK, Dimopoulos MA, Kastritis E, Terpos E, Nahi H, Goldschmidt H, Hillengass J, Leleu X, Beksac M, Alsina M, Oriol A, Cavo M, Ocio EM, Mateos MV, O’Donnell EK, Vij R, Lokhorst HM, van de Donk NWCJ, Min C, Mark T, Turesson I, Hansson M, Ludwig H, Jagannath S, Delforge M, Kyriakou C, Hari P, Mellqvist U, Usmani SZ, Dytfeld D, Badros AZ, Moreau P, Kim K, Otero PR, Lee JH, Shustik C, Waller D, Chng WJ, Ozaki S, Lee JJ, de la Rubia J, Eom HS, Rosinol L, Lahuerta JJ, Sureda A, Kim JS, Durie BGM (2017) Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia 31:2443–2448.  https://doi.org/10.1038/leu.2017.138 CrossRefGoogle Scholar
  3. 3.
    San Miguel J, Weisel K, Moreau P et al (2013) Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 14:1055–1066.  https://doi.org/10.1016/S1470-2045(13)70380-2 CrossRefGoogle Scholar
  4. 4.
    Dimopoulos MA, Palumbo A, Corradini P, Cavo M, Delforge M, di Raimondo F, Weisel KC, Oriol A, Hansson M, Vacca A, Blanchard MJ, Goldschmidt H, Doyen C, Kaiser M, Petrini M, Anttila P, Cafro AM, Raymakers R, San-Miguel J, de Arriba F, Knop S, Rollig C, Ocio EM, Morgan G, Miller N, Simcock M, Peluso T, Herring J, Sternas L, Zaki MH, Moreau P (2016) Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUSTM (MM-010): a phase 3b study in refractory multiple myeloma. Blood. 128:497–503.  https://doi.org/10.1182/blood-2016-02-700872 CrossRefGoogle Scholar
  5. 5.
    Baz RC, Martin TG, Lin H-Y et al (2016) Randomized multicenter phase II study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 127:2561–2568.  https://doi.org/10.1182/blood-2015-11-682518 CrossRefGoogle Scholar
  6. 6.
    Garderet L, Kuhnowski F, Berge B, Roussel M, Escoffre-Barbe M, Lafon I, Facon T, Leleu X, Karlin L, Perrot A, Moreau P, Marit G, Stoppa AM, Royer B, Chaleteix C, Tiab M, Araujo C, Lenain P, Macro M, Voog E, Benboubker L, Allangba O, Jourdan E, Orsini-Piocelle F, Brechignac S, Eveillard JR, Belhadj K, Wetterwald M, Pegourie B, Jaccard A, Eisenmann JC, Glaisner S, Mohty M, Hulin C, Loiseau HA, Mathiot C, Attal M (2018) Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood. 132:2555–2563.  https://doi.org/10.1182/blood-2018-07-863829 CrossRefGoogle Scholar
  7. 7.
    Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, la Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omede P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A (2013) Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study. Blood 122:2799–2806.  https://doi.org/10.1182/blood-2013-03-488676 CrossRefGoogle Scholar
  8. 8.
    Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BGM, Miguel JFS (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538–e548.  https://doi.org/10.1016/S1470-2045(14)70442-5 CrossRefGoogle Scholar
  9. 9.
    Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H (2016) International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17:e328–e346.  https://doi.org/10.1016/S1470-2045(16)30206-6 CrossRefGoogle Scholar
  10. 10.
    Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BGM (2015) Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood 126:2284–2290.  https://doi.org/10.1182/blood-2015-05-643320 CrossRefGoogle Scholar
  11. 11.
    Bringhen S, Mina R, Cafro AM, Liberati AM, Spada S, Belotti A, Gaidano G, Patriarca F, Troia R, Fanin R, de Paoli L, Rossi G, Lombardo A, Bertazzoni P, Palumbo A, Sonneveld P, Boccadoro M (2018) Once-weekly carfilzomib, pomalidomide, and low-dose dexamethasone for relapsed/refractory myeloma: a phase I/II study. Leukemia 32:1803–1807.  https://doi.org/10.1038/s41375-018-0024-1 CrossRefGoogle Scholar
  12. 12.
    Chari A, Lonial S, Suvannasankha A et al (2015) Open-label, multicenter, phase 1b study of Daratumumab in combination with Pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma. Blood 126:508–508CrossRefGoogle Scholar
  13. 13.
    Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, Leleu X, LeBlanc R, Suzuki K, Raab MS, Richardson PG, Popa McKiver M, Jou YM, Shelat SG, Robbins M, Rafferty B, San-Miguel J (2018) Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med 379:1811–1822.  https://doi.org/10.1056/NEJMoa1805762 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sabrina Trudel
    • 1
  • Benoît Tessoulin
    • 1
    • 2
  • Maxime Jullien
    • 1
  • Nicolas Blin
    • 1
  • Thomas Gastinne
    • 1
  • Béatrice Mahé
    • 1
  • Viviane Dubruille
    • 1
  • Antoine Bonnet
    • 1
  • Anne Lok
    • 1
  • Patrice Chevallier
    • 1
  • Pierre Peterlin
    • 1
  • Alice Garnier
    • 1
  • Thierry Guillaume
    • 1
  • Amandine Le Bourgeois
    • 1
  • Steven Le Gouill
    • 1
    • 2
    • 3
  • Philippe Moreau
    • 1
    • 2
    • 3
  • Cyrille Touzeau
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of HematologyCentre Hospitalier UniversitaireNantesFrance
  2. 2.CRCINA, INSERM, CNRSUniversité d’Angers, Université de NantesNantesFrance
  3. 3.Site de Recherche Intégrée sur le Cancer (SIRIC) «ILIAD»NantesFrance
  4. 4.Service d’hématologie CliniqueCentre Hospitalier UniversitaireNantesFrance

Personalised recommendations