학술논문
Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial
Document Type
Original Paper
Author
van de Loosdrecht, A. A.; Cremers, E. M. P.; Alhan, C.; Duetz, C.; in ’t Hout, F. E. M.; Visser-Wisselaar, H. A.; Chitu, D. A.; Verbrugge, A.; Cunha, S. M.; Ossenkoppele, G. J.; Janssen, J. J. W. M.; Klein, S. K.; Vellenga, E.; Huls, G. A.; Muus, P.; Langemeijer, S. M. C.; de Greef, G. E.; te Boekhorst, P. A. W.; Raaijmakers, M. H. G.; van Marwijk Kooy, M.; Legdeur, M. C.; Wegman, J. J.; Deenik, W.; de Weerdt, O.; van Maanen-Lamme, T. M.; Jobse, P.; van Kampen, R. J. W.; Beeker, A.; Wijermans, P. W.; Biemond, B. J.; Tanis, B. C.; van Esser, J. W. J.; Schaar, C. G.; Noordzij-Nooteboom, H. S.; Jacobs, E. M. G.; de Graaf, A. O.; Jongen-Lavrencic, M.; Stevens-Kroef, M. J. P. L.; Westers, T. M.; Jansen, J. H.
Source
Leukemia. 38(4):840-850
Subject
Language
English
ISSN
0887-6924
1476-5551
1476-5551
Abstract
A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).