1. Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes:the HOVON89 trial
- Author
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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., 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., and Jansen, J. H.
- 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).
- Published
- 2024