TY - JOUR
T1 - Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes
T2 - the HOVON89 trial
AU - van de Loosdrecht, A. A.
AU - Cremers, E. M. P.
AU - Alhan, C.
AU - Duetz, C.
AU - in ’t Hout, F. E. M.
AU - Visser-Wisselaar, H. A.
AU - Chitu, D. A.
AU - Verbrugge, A.
AU - Cunha, S. M.
AU - Ossenkoppele, G. J.
AU - Janssen, J. J. W. M.
AU - Klein, S. K.
AU - Vellenga, E.
AU - Huls, G. A.
AU - Muus, P.
AU - Langemeijer, S. M. C.
AU - de Greef, G. E.
AU - te Boekhorst, P. A. W.
AU - Raaijmakers, M. H. G.
AU - van Marwijk Kooy, M.
AU - Legdeur, M. C.
AU - Wegman, J. J.
AU - Deenik, W.
AU - de Weerdt, O.
AU - van Maanen-Lamme, T. M.
AU - Jobse, P.
AU - van Kampen, R. J. W.
AU - Beeker, A.
AU - Wijermans, P. W.
AU - Biemond, B. J.
AU - Tanis, B. C.
AU - van Esser, J. W. J.
AU - Schaar, C. G.
AU - Noordzij-Nooteboom, H. S.
AU - Jacobs, E. M. G.
AU - de Graaf, A. O.
AU - Jongen-Lavrencic, M.
AU - Stevens-Kroef, M. J. P. L.
AU - Westers, T. M.
AU - Jansen, J. H.
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024/4
Y1 - 2024/4
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85183723258&partnerID=8YFLogxK
U2 - 10.1038/s41375-024-02161-6
DO - 10.1038/s41375-024-02161-6
M3 - Article
C2 - 38297135
SN - 0887-6924
VL - 38
SP - 840
EP - 850
JO - Leukemia
JF - Leukemia
IS - 4
ER -