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Observational Study
. 2023 May 22;13(1):85.
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 #  1 , Erik van Werkhoven #  2 , Avinash G Dinmohamed  3   4   5 , Marcel Nijland  6 , Aeilko H Zwinderman  7 , Patrick M Bossuyt  7 , Martine S Veldhuis  3 , Emma G G M Rutten  8 , Rogier Mous  9 , Joost S P Vermaat  10 , Yorick Sandberg  11 , Eva de Jongh  12 , Yavuz M Bilgin  13 , Rinske Boersma  14 , Harry Koene  15 , Marie José Kersten  3 , Daphne de Jong  8 , Martine E D Chamuleau  3
Affiliations
Observational Study

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

A Vera de Jonge et al. Blood Cancer J. .

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.

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Conflict of interest statement

AVDJ, EVW, AGD, MN, AHZ, PMB, MSV, EGGMR, RM, JSPV, YS, EDJ, YM, RB, HK, and DDJ declare no competing financial interests. MJK received honoraria from Kite, Novartis, and Miltenyi Biotech, Roche, and Bristol Myers Squibb/Celgene; consultancy or advisory role for Kite, Roche, Bristol Myers Squibb/Celgene, Novartis, and Miltenyi Biotech; research funding from Kite, Roche, Takeda, and Celgene (all to institution); and travel support from Kite, Roche, Novartis, and Miltenyi Biotech. MEDC received research funding from BMS/Celgene, Gilead and GenMAb. Advisory role for AbbVie and Novartis.

Figures

Fig. 1
Fig. 1. Flow chart of patient selection.
Flow chart of the patients included in the HOVON-130 and HOVON-900 for the current comparison.
Fig. 2
Fig. 2. Overall survival analysis in MYC-R patients.
Overall survival analysis in MYC-R patients treated with R2CHOP in blue versus R-CHOP in red in A an unadjusted comparison of the overall survival by treatment, B comparison of the overall survival in the patients one-to-one matched on IPI risk score, and C doubly robust analysis using AIPTW with IPCW estimate of overall survival. Error bars represent 95% confidence interval.
Fig. 3
Fig. 3. Progression-free survival analysis in MYC-R patients.
Progression-free survival analysis in MYC-R patients treated with R2CHOP in blue versus R-CHOP in red in A an unadjusted comparison of the overall survival by treatment, B comparison of the progression-free survival in the patients one-to-one matched on IPI risk score and C doubly robust analysis using AIPTW with IPCW estimate of progression-free survival. Error bars represent 95% confidence interval.
Fig. 4
Fig. 4. Subgroup analysis of overall survival per rearrangement status.
MYC-R patients treated with R2CHOP in blue versus R-CHOP in red in an unadjusted comparison depicted for A single-hit patients and B double/triple-hit patients.
Fig. 5
Fig. 5. Subgroup analysis of progression-free survival per rearrangement status.
MYC-R patients treated with R2CHOP in blue versus R-CHOP in red in an unadjusted comparison depicted for A single-hit patients and B double/triple-hit patients.
See this image and copyright information in PMC

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