A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide

Gamberi, B.; Berthou, C.; Hernandez, M.; Semenzato, G.; Tholouli, E.; Hájek, R.; Caers, Jo; Dimopoulos, M.; Minnema, M. C.; Andreasson, B.; Parreira, J.; Crotty, G.; Remes, K.; Kueenburg, E.; Rosettani, B.; Di Micco, A.; Peters, S.; Bacon, P.; Blau, I. W.

doi:10.1016/j.clml.2020.05.006

Article (Scientific journals)

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide

Gamberi, B.; Berthou, C.; Hernandez, M. et al.

2020 • In Clinical Lymphoma, Myeloma and Leukemia, 20, p. 629-e644

Peer reviewed

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https://hdl.handle.net/2268/249344

DOI
10.1016/j.clml.2020.05.006

PubMed
32605897

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Keywords :

Adverse events of special interest; Immunomodulatory; Incidence rate; Prospective; Real-world

Abstract :

[en] Introduction: Lenalidomide plus dexamethasone is effective and well tolerated in relapsed/refractory multiple myeloma (RRMM). In this observational, noninterventional European post-authorization safety study, the safety profile of lenalidomide plus dexamethasone was investigated and compared with that of other agents in the treatment of RRMM in a real-world setting. Patients and Methods: Patients had received ≥ 1 prior antimyeloma therapy; prior lenalidomide was excluded. Treatment was per investigator's routine practice. Adverse events were analyzed by incidence rates per 100 person-years to account for differences in observation length and treatment duration. Results: In total, 2150 patients initiated lenalidomide, and 1479 initiated any other antimyeloma therapy, predominately bortezomib (80.3%), which was primarily administered intravenously (74.3%). The incidence rate of neuropathy was lower with lenalidomide (10.5) than with bortezomib (78.9) or thalidomide (38.7). Lenalidomide also had a lower incidence rate of infections (68.7) versus bortezomib (95.9) and thalidomide (76.0). Conversely, the incidence rate of neutropenia was higher with lenalidomide (38.0) than with bortezomib (18.2) or thalidomide (25.7). The incidence rates of thrombocytopenia were 24.4, 40.4, and 14.4 with lenalidomide, bortezomib, and thalidomide, respectively. Conclusion: No new safety signals for lenalidomide were identified in this study, which is the largest prospective real-world European study of lenalidomide in patients with RRMM to date. These results confirm that the safety profile of lenalidomide plus dexamethasone in RRMM in a real-world setting is comparable to that reported in clinical trials. © 2020 The AuthorsGiven the key role of lenalidomide in the treatment of relapsed/refractory multiple myeloma, it is important to evaluate the safety of lenalidomide in real-world populations of patients who may not qualify for clinical trial participation. This noninterventional, European post-authorization safety study confirms that the real-world safety profile of lenalidomide is similar to what has been reported in clinical trials. © 2020 The Authors

Disciplines :

Hematology

Author, co-author :

Gamberi, B.; Department of Hematology, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy

Berthou, C.; Centre Hospitalier Régional Universitaire, Hôpital Auguste Morvan, Brest, France

Hernandez, M.; Hemotherapy Service, Hospital Universitario de Canarias, Tenerife, Spain

Semenzato, G.; Department of Medicine, Azienda Ospedale Università di Padova, Padova, Italy

Tholouli, E.; Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom

Hájek, R.; Department of Clinic Subjects, University Hospital Ostrava and Faculty of Medicine Ostrava, Ostrava, Czech Republic

Caers, Jo ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques

Dimopoulos, M.; National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

Minnema, M. C.; Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands

Andreasson, B.; Uddevalla Hospital, NU Hospital Group, Uddavella, Sweden

More authors (9 more)

Language :

English

Title :

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide

Publication date :

2020

Journal title :

Clinical Lymphoma, Myeloma and Leukemia

ISSN :

2152-2650

eISSN :

2152-2669

Publisher :

Elsevier Inc.

Volume :

Pages :

e629-e644

Peer reviewed :

Peer reviewed

Funders :

BMS - Bristol-Myers Squibb [BE]
Novartis [BE]
Takeda Pharmaceutical Company

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Bibliography

Mey, U.J.M., Leitner, C., Driessen, C., Cathomas, R., Klingbiel, D., Hitz, F., Improved survival of older patients with multiple myeloma in the era of novel agents. Hematol Oncol 34 (2016), 217–223.
Sonneveld, P., Broijl, A., Treatment of relapsed and refractory multiple myeloma. Haematologica 101 (2016), 396–406.
Rajkumar, V., Myeloma today: disease definitions and treatment advances. Am J Hematol 91 (2016), 90–100.
Moreau, P., de Wit, E., Recent progress in relapsed multiple myeloma therapy: implications for treatment decisions. Br J Haematol 179 (2017), 198–218.
Binder, M., Rajkumar, S.V., Ketterling, R.P., et al. Occurrence and prognostic significance of cytogenetic evolution in patients with multiple myeloma. Blood Cancer J, 6, 2016, e401.
Robak, P., Drozdz, I., Szemraj, J., Robak, T., Drug resistance in multiple myeloma. Cancer Treat Rev 70 (2018), 199–208.
Lohr, J.G., Stojanov, P., Carter, S.L., et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 25 (2014), 91–101.
Leich, E., Weissbach, S., Klein, H.-U., et al. Multiple myeloma is affected by multiple and heterogeneous somatic mutations in adhesion- and receptor tyrosine kinase signaling molecules. Blood Cancer J, 3, 2013, e102.
Keats, J.J., Chesi, M., Egan, J.B., et al. Clonal competition with alternating dominance in multiple myeloma. Blood 120 (2012), 1067–1076.
Kumar, S.K., Dimopoulos, M.A., Kastritis, E., et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia 31 (2017), 2443–2448.
Kumar, S.K., Therneau, T.M., Gertz, M.A., et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc 79 (2004), 867–874.
Holstein, S.A., Suman, V.J., McCarthy, P.L., Update on the role of lenalidomide in patients with multiple myeloma. Ther Adv Hematol 9 (2018), 175–190.
Revlimid (lenalidomide). [Package insert], 2019, Celgene Corporation, Summit, NJ.
Lu, G., Middleton, R.E., Sun, H., et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins. Science 343 (2014), 305–309.
Lopez-Girona, A., Mendy, D., Ito, T., et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia 26 (2012), 2326–2335.
Bjorklund, C.C., Lu, L., Kang, J., et al. Rate of CRL4(CRBN) substrate ikaros and aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-myc and IRF4. Blood Cancer J, 5, 2015, e354.
Kronke, J., Udeshi, N.D., Narla, A., et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343 (2014), 301–305.
Dimopoulos, M., Spencer, A., Attal, M., et al., Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357 (2007), 2123–2132.
Weber, D.M., Chen, C., Niesvizky, R., et al., Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357 (2007), 2133–2142.
Richardson, P.G., Blood, E., Mitsiades, C.S., et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108 (2006), 3458–3464.
Chanan-Khan, A.A., Lonial, S., Weber, D., et al. Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients ≥ 65 years old with relapsed or refractory multiple myeloma. Int J Hematol 96 (2012), 254–262.
Revlimid (lenalidomide). [Summary of product characteristics]. European Medicines Agency, 2019.
Dimopoulos, M.A., Chen, C., Spencer, A., et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23 (2009), 2147–2152.
Richardson, P.G., San Miguel, J.F., Moreau, P., et al. Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting. Blood Cancer J, 8, 2018, 109.
Velcade (bortezomib). [Summary of product characteristics]. European Medicines Agency, 2019.
Velcade (bortezomib) for injection, for subcutaneous or intravenous use, ed. [Package insert], 2019, Millennium Pharmaceuticals, Inc, Cambridge, MA.
Dimopoulos, M.A., Richardson, P.G., Brandenburg, N., et al. A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 119 (2012), 2764–2767.
Musto, P., Anderson, K.C., Attal, M., et al., International Myeloma Working Group. Second primary malignancies in multiple myeloma: an overview and IMWG consensus. Ann Oncol 28 (2016), 228–245.
Faiman, B., Sidana, S., Elson, P., et al. Lenalidomide related diarrhea correlates with survival in multiple myeloma [Abstract]. Blood, 122, 2013, 5397.
Knauf, W., Aldaoud, A., Losem, C., et al. Lenalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: final results of a non-interventional study and comparison with the pivotal phase 3 clinical trials. Leuk Res 68 (2018), 90–97.
Palumbo, A., Rajkumar, S.V., Dimopoulos, M.A., et al., International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 22 (2008), 414–423.