{Reference Type}: Clinical Trial, Phase II
{Title}: Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.
{Author}: van de Loosdrecht AA;Cremers EMP;Alhan C;Duetz C;In 't Hout FEM;Visser-Wisselaar HA;Chitu DA;Verbrugge A;Cunha SM;Ossenkoppele GJ;Janssen JJWM;Klein SK;Vellenga E;Huls GA;Muus P;Langemeijer SMC;de Greef GE;Te Boekhorst PAW;Raaijmakers MHG;van Marwijk Kooy M;Legdeur MC;Wegman JJ;Deenik W;de Weerdt O;van Maanen-Lamme TM;Jobse P;van Kampen RJW;Beeker A;Wijermans PW;Biemond BJ;Tanis BC;van Esser JWJ;Schaar CG;Noordzij-Nooteboom HS;Jacobs EMG;de Graaf AO;Jongen-Lavrencic M;Stevens-Kroef MJPL;Westers TM;Jansen JH;
{Journal}: Leukemia
{Volume}: 38
{Issue}: 4
{Year}: 2024 Apr 31
{Factor}: 12.883
{DOI}: 10.1038/s41375-024-02161-6
{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).