Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial

期刊论文
出版模式：

开放获取
发表日期：

2024年1月31日

查看全文

A. A. van de Loosdrecht,
E. M. P. Cremers,
C. Alhan,
C. Duetz,
F. E. M. in ’t Hout,
H. A. Visser-Wisselaar,
D. A. Chitu,
A. Verbrugge,
S. M. Cunha,
G. J. Ossenkoppele,
J. J. W. M. Janssen,
S. K. Klein,
E. Vellenga,
G. A. Huls,
P. Muus,
S. M. C. Langemeijer,
G. E. de Greef,
P. A. W. te Boekhorst,
M. H. G. Raaijmakers,
M. van Marwijk Kooy,
M. C. Legdeur,
J. J. Wegman,
W. Deenik,
O. de Weerdt,
T. M. van Maanen-Lamme,
P. Jobse,
R. J. W. van Kampen,
A. Beeker,
P. W. Wijermans,
B. J. Biemond,
B. C. Tanis,
J. W. J. van Esser,
C. G. Schaar,
H. S. Noordzij-Nooteboom,
E. M. G. Jacobs,
A. O. de Graaf,
M. Jongen-Lavrencic,
M. J. P. L. Stevens-Kroef,
T. M. Westers,
J. H. Jansen

摘要

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).