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

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

doi:10.1038/s41375-024-02161-6

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

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 KooyM. 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

^*Corresponding author for this work

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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).

Original language	English
Pages (from-to)	840-850
Number of pages	11
Journal	Leukemia
Volume	38
Issue number	4
Early online date	31 Jan 2024
DOIs	https://doi.org/10.1038/s41375-024-02161-6
Publication status	Published - Apr 2024

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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., ... Jansen, J. H. (2024). Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial. Leukemia, 38(4), 840-850. https://doi.org/10.1038/s41375-024-02161-6

@article{703c590d14904dab8eafb88a413f86ac,

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

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).",

author = "{van de Loosdrecht}, {A. A.} and Cremers, {E. M.P.} and C. Alhan and C. Duetz and {in {\textquoteright}t Hout}, {F. E.M.} and Visser-Wisselaar, {H. A.} and Chitu, {D. A.} and A. Verbrugge and Cunha, {S. M.} and Ossenkoppele, {G. J.} and Janssen, {J. J.W.M.} and Klein, {S. K.} and E. Vellenga and Huls, {G. A.} and P. Muus and Langemeijer, {S. M.C.} and {de Greef}, {G. E.} and {te Boekhorst}, {P. A.W.} and Raaijmakers, {M. H.G.} and {van Marwijk Kooy}, M. and Legdeur, {M. C.} and Wegman, {J. J.} and W. Deenik and {de Weerdt}, O. and {van Maanen-Lamme}, {T. M.} and P. Jobse and {van Kampen}, {R. J.W.} and A. Beeker and Wijermans, {P. W.} and Biemond, {B. J.} and Tanis, {B. C.} and {van Esser}, {J. W.J.} and Schaar, {C. G.} and Noordzij-Nooteboom, {H. S.} and Jacobs, {E. M.G.} and {de Graaf}, {A. O.} and M. Jongen-Lavrencic and Stevens-Kroef, {M. J.P.L.} and Westers, {T. M.} and Jansen, {J. H.}",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = apr,

doi = "10.1038/s41375-024-02161-6",

language = "English",

volume = "38",

pages = "840--850",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "4",

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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 2024, 'Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial', Leukemia, vol. 38, no. 4, pp. 840-850. https://doi.org/10.1038/s41375-024-02161-6

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.

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).

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U2 - 10.1038/s41375-024-02161-6

DO - 10.1038/s41375-024-02161-6

M3 - Article

C2 - 38297135

AN - SCOPUS:85183723258

SN - 0887-6924

VL - 38

SP - 840

EP - 850

JO - Leukemia

JF - Leukemia

IS - 4

ER -

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

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