Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial

Abstract

The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3–4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = .817) or hemorrhagic events (p = 1.000). Grade 3–4 non-hematologic TEAEs were rare (the incidence of grade 3–4 pneumonia, e.g. was 5.6% in the lenalidomide group and 2.5% in the placebo group). Common grade 1–2 non-hematologic TEAEs did not require dose modifications or treatment discontinuation. Acute myeloid leukemia and second primary malignancies incidence was similar across treatment groups. Lenalidomide had a predictable and manageable safety profile in lower-risk non-del(5q) MDS patients ineligible/refractory to ESAs. Guidance on managing lenalidomide-related TEAEs is provided to help maintain patients on therapy to achieve maximum clinical benefit.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01029262

Keywords:

• Myeloid leukemias and dysplasias
• manipulation of the immune response
• immunotherapy

Acknowledgements

A. A., P. F., G. G.-M., S. L. G., S. G., A. J., N. V., and V. S. contributed to collection of data. J. Z. performed the statistical analyses. All authors were involved in the analysis and interpretation of the data, review and revision of the work, and approval of the final version of the manuscript.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1421758. The authors received editorial and writing support provided by Christian Geest, PhD, from Excerpta Medica, funded by Celgene Corporation. The authors are fully responsible for all content and editorial decisions.

A. Almeida: Bristol-Myers Squibb – speakers bureau; Celgene Corporation – honoraria, consultancy, speakers bureau, research funding; Novartis – honoraria, consultancy, speakers bureau; Shire – speakers bureau. P. Fenaux and G. Garcia-Manero: no conflicts of interest to disclose. S. L. Goldberg: ARIAD Pharmaceuticals – research funding; Astellas Pharma – research funding; Bristol-Myers Squibb – consultancy, speakers bureau, research funding; COTA Inc. – employment, leadership, equity ownership; Celator Pharmaceuticals – research funding; Celgene Corporation – personal fees; Novartis – consultancy, speakers bureau, research funding, expert testimony; Pfizer – honoraria, travel and accommodation expense. S. Gröpper: No conflict of interest to declare. A. Jonasova: Celgene Corporation – research funding, travel and accommodation expenses. N. Vey: Amgen – honoraria; Celgene Corporation – honoraria; Roche – honoraria; Sunesis Pharmaceuticals – honoraria. C. Castaneda, J. Zhong, and C. L. Beach: Celgene Corporation – employment and equity ownership. V. Santini: Celgene Corporation – honoraria, research funding; Janssen Pharmaceuticals – honoraria; Novartis – honoraria; Otsuka – honoraria; Amgen – honoraria; AbbVie – honoraria.

Additional information

Funding

This study was supported by Celgene Corporation, Summit, NJ, USA.