A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

A. Vera de Jonge; Erik van Werkhoven; Avinash G. Dinmohamed; Marcel Nijland; Aeilko H. Zwinderman; Patrick M. Bossuyt; Martine S. Veldhuis; Emma G.G.M. Rutten; Rogier Mous; Joost S.P. Vermaat; Yorick Sandberg; Eva de Jongh; Yavuz M. Bilgin; Rinske Boersma; Harry Koene; Marie José Kersten; Daphne de Jong; Martine E.D. Chamuleau

doi:10.1038/s41408-023-00854-2

A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

A. Vera de Jonge^*, Erik van Werkhoven, Avinash G. Dinmohamed, Marcel Nijland, Aeilko H. Zwinderman, Patrick M. Bossuyt, Martine S. Veldhuis, Emma G.G.M. Rutten, Rogier Mous, Joost S.P. Vermaat, Yorick Sandberg, Eva de Jongh, Yavuz M. Bilgin, Rinske Boersma, Harry Koene, Marie José Kersten, Daphne de Jong, Martine E.D. Chamuleau

^*Corresponding author for this work

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Abstract

Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients. [Figure not available: see fulltext.]

Original language	English
Article number	85
Journal	Blood Cancer Journal
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41408-023-00854-2
Publication status	Published - 22 May 2023

Bibliographical note

ACKNOWLEDGEMENTS:
The authors thank all study investigators and coordinators of the participating site of the HOVON-130 and HOVON-900 studies, the data-managers of the Netherlands Cancer Registry who helped retrieve the data, in particular Henrike Bretveld, and the HOVON Data Center in Rotterdam. Celgene provided financial support of the HOVON-130 trial (004414). Dutch Cancer Society (KWF) provided financial support of the HOVON-900 (VUMC 2013-6269) and HOVON-130 (EMCR 2014-7436).

Publisher Copyright:
© 2023, The Author(s).

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de Jonge, A. V., van Werkhoven, E., Dinmohamed, A. G., Nijland, M., Zwinderman, A. H., Bossuyt, P. M., Veldhuis, M. S., Rutten, E. G. G. M., Mous, R., Vermaat, J. S. P., Sandberg, Y., de Jongh, E., Bilgin, Y. M., Boersma, R., Koene, H., Kersten, M. J., de Jong, D., & Chamuleau, M. E. D. (2023). A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients. Blood Cancer Journal, 13(1), Article 85. https://doi.org/10.1038/s41408-023-00854-2

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title = "A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients",

abstract = "Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients. [Figure not available: see fulltext.]",

author = "{de Jonge}, {A. Vera} and {van Werkhoven}, Erik and Dinmohamed, {Avinash G.} and Marcel Nijland and Zwinderman, {Aeilko H.} and Bossuyt, {Patrick M.} and Veldhuis, {Martine S.} and Rutten, {Emma G.G.M.} and Rogier Mous and Vermaat, {Joost S.P.} and Yorick Sandberg and {de Jongh}, Eva and Bilgin, {Yavuz M.} and Rinske Boersma and Harry Koene and Kersten, {Marie Jos{\'e}} and {de Jong}, Daphne and Chamuleau, {Martine E.D.}",

note = "ACKNOWLEDGEMENTS: The authors thank all study investigators and coordinators of the participating site of the HOVON-130 and HOVON-900 studies, the data-managers of the Netherlands Cancer Registry who helped retrieve the data, in particular Henrike Bretveld, and the HOVON Data Center in Rotterdam. Celgene provided financial support of the HOVON-130 trial (004414). Dutch Cancer Society (KWF) provided financial support of the HOVON-900 (VUMC 2013-6269) and HOVON-130 (EMCR 2014-7436). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

day = "22",

doi = "10.1038/s41408-023-00854-2",

language = "English",

volume = "13",

journal = "Blood Cancer Journal",

issn = "2044-5385",

publisher = "Nature Publishing Group",

number = "1",

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de Jonge, AV, van Werkhoven, E , Dinmohamed, AG, Nijland, M, Zwinderman, AH, Bossuyt, PM, Veldhuis, MS, Rutten, EGGM, Mous, R, Vermaat, JSP, Sandberg, Y, de Jongh, E, Bilgin, YM, Boersma, R, Koene, H, Kersten, MJ, de Jong, D & Chamuleau, MED 2023, 'A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients', Blood Cancer Journal, vol. 13, no. 1, 85. https://doi.org/10.1038/s41408-023-00854-2

TY - JOUR

T1 - A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

AU - de Jonge, A. Vera

AU - van Werkhoven, Erik

AU - Dinmohamed, Avinash G.

AU - Nijland, Marcel

AU - Zwinderman, Aeilko H.

AU - Bossuyt, Patrick M.

AU - Veldhuis, Martine S.

AU - Rutten, Emma G.G.M.

AU - Mous, Rogier

AU - Vermaat, Joost S.P.

AU - Sandberg, Yorick

AU - de Jongh, Eva

AU - Bilgin, Yavuz M.

AU - Boersma, Rinske

AU - Koene, Harry

AU - Kersten, Marie José

AU - de Jong, Daphne

AU - Chamuleau, Martine E.D.

N1 - ACKNOWLEDGEMENTS: The authors thank all study investigators and coordinators of the participating site of the HOVON-130 and HOVON-900 studies, the data-managers of the Netherlands Cancer Registry who helped retrieve the data, in particular Henrike Bretveld, and the HOVON Data Center in Rotterdam. Celgene provided financial support of the HOVON-130 trial (004414). Dutch Cancer Society (KWF) provided financial support of the HOVON-900 (VUMC 2013-6269) and HOVON-130 (EMCR 2014-7436). Publisher Copyright: © 2023, The Author(s).

PY - 2023/5/22

Y1 - 2023/5/22

N2 - Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients. [Figure not available: see fulltext.]

AB - Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients. [Figure not available: see fulltext.]

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U2 - 10.1038/s41408-023-00854-2

DO - 10.1038/s41408-023-00854-2

M3 - Article

C2 - 37217463

AN - SCOPUS:85159844803

SN - 2044-5385

VL - 13

JO - Blood Cancer Journal

JF - Blood Cancer Journal

IS - 1

M1 - 85

ER -

A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

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