-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

851 A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC-Rearranged DLBCL Patients

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Predictors of Outcome
Hematology Disease Topics & Pathways:
Research, clinical trials, adult, Lymphomas, non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Combination therapy, Diseases, aggressive lymphoma, Therapies, registries, Lymphoid Malignancies, Study Population, Human
Monday, December 12, 2022: 3:45 PM

Vera de Jonge1*, Erik D. van Werkhoven, MSc2*, Avinash G. Dinmohamed3*, Marcel Nijland, MD, PhD4*, Aeilko H. Zwinderman5*, Patrick M. Bossuyt6*, Martine S. Veldhuis7*, Emma G.G.M. Rutten8*, Rogier Mous9*, Joost S.P. Vermaat, MD, PhD10, Yorick Sandberg, MD11*, Eva de Jongh, MD12*, Yavuz M. Bilgin, MD PhD13*, Rinske Boersma, MD14*, Harry R. Koene, MD, PhD15*, Marie Jose Kersten, MD, PhD16, Daphne de Jong, MD, PhD17* and Martine E.D. Chamuleau, MD, PhD18

1Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
2Hovon data center, department of Hematology, Erasmus MC Cancer institute, Rotterdam, Netherlands
3Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands
4Department of Hematology, University Medical Center Groningen and University of Groningen, Groningen, Netherlands
5Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, NLD
6Department of Clinical Epidemiology, Biostatistics, Amsterdam UMC, location University of Amsterdam, Amsterdam, NLD
7Department of Hematology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, NLD
8Department of Pathology, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, NLD
9Department of Hematology, Universitair Medisch Centrum Utrecht, Utrecht, NH, Netherlands
10Department of Hematology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
11Department of Internal Medicine, Maasstad Hospital, Rotterdam, Netherlands
12Department of Hematology, Albert Schweitzer Hospital, Dordrecht, Netherlands
13Department of Internal Medicine, Admiraal de Ruijter Hospital, Goes, Netherlands
14Department of Internal Medicine, Amphia Hospital, Breda, Netherlands
15Department of Hematology, St. Antonius Hospital, Nieuwegein, NLD
16Department of Hematology, Academic Medical Center, Amsterdam, Noord Holland, Netherlands
17Amsterdam UMC, Vrije Universiteit Amsterdam, department of Pathology, Cancer Center Amsterdam, Amsterdam, Netherlands
18Amsterdam UMC, Vrije Universiteit Amsterdam, department of Hematology, Cancer Center Amsterdam, Amsterdam, Netherlands


Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) generally have a poor prognosis following standard treatment with R-CHOP. 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 (CMR) rates and survival as more intensive chemotherapy regimens such as DA-EPOCH-R [Chamuleau, Haematologica 2020]. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed DLBCL patients treated with R-CHOP in the Netherlands, including MYC-R patients who were not included in the interventional trial due to logistic reasons. These two cohorts enable to evaluate the added value of lenalidomide to R-CHOP in first-line treatment of newly diagnosed MYC-R DLBCL patients.


In the single-arm, phase-II HOVON-130 trial, MYC-R DLBCL patients ≥ 18 years were treated with R-CHOP21 plus lenalidomide 15 mg day 1-15 for 6 cycles [Chamuleau, Haematologica 2020]. Additional inclusion criteria were Ann-Arbor stage II-IV, WHO performance status 0-3, ≥ one lesion of ≥ 1.5 cm on contrast-enhanced CT scan and ≥ one FDG-positive lesion on PET-CT scan.

In the observational screening study HOVON-900, MYC, BCL2 and BCL6 fluorescent in situ hybridization (FISH) diagnostics were advocated as part of routine procedures and reviewed by the HOVON Pathology Facility. As a control group, we selected MYC-R patients from this observational cohort who met the inclusion criteria for the interventional trial but were not included, and who were treated with standard R-CHOP. Clinical information at presentation and treatment and outcome data were retrieved from the Netherlands Cancer Registry.

We explored three statistical methods that account for baseline imbalances. First, we used multivariable regression, with baseline variables as covariates in the model. Second, we performed one-to-one matching on the IPI risk (low, intermediate, or high). Third, we performed inverse probability of treatment weighting (IPTW) using a propensity score. We calculated a propensity score for being included in the HOVON-130 trial based on the separate components of the IPI score (i.e., age, Ann Arbor stage, WHO performance score, extra-nodal localizations, serum LDH level), sex and rearrangement status. To allow for some degree of misspecification of the model for the propensity score, we used a doubly-robust estimator. Subgroup analyses were performed in single hit (SH: only MYC rearrangement), versus double hit and triple hit (DH/TH: MYC rearrangement with BCL2 and/or BCL6 rearrangement).


Patients from the interventional trial treated with R2CHOP (n=77) were younger than patients in the control cohort (n=56) treated with R-CHOP (median age 63 versus 70 years, p=0.018) and they were more likely to have a lower WHO performance score (p=0.013). Ann Arbor stage, LDH level, number of extranodal localizations and median days before treatment (15 and 19 in the R-CHOP and R2CHOP group, respectively) did not significantly differ between the groups.

Complete remission rates were 69.8% and 80.5% in the R-CHOP and R2CHOP group, respectively (p=0.209).

Multivariable analysis, 1:1 matching and weighting using the propensity score consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.53, and 0.59 (Figure 1A), respectively, for OS, and 0.59, 0.53, and 0.60 for PFS (Figure 1B). In the subgroups determined by rearrangement status, we performed unadjusted OS and PFS analysis only, because we were not able to adjust for baseline imbalances because of the low number of events within the subgroups. Both SH patients and DH/TH patients tended to have a longer OS when treated with R2CHOP with HRs of 0.34 and 0.57, respectively. Similarly, for PFS the HRs were 0.66 in the SH subgroup and 0.48 in the DH/TH subgroup.


In conclusion, this propensity score-adjusted comparison study supports the addition of lenalidomide to R-CHOP as a valuable treatment option for MYC-R DLBCL patients. R2CHOP can be administered on a full outpatient basis, with minimal hospitalization visits. Future studies will explore whether adding next-generation cereblon targeting antigens to R-CHOP can improve the observed effects.

Disclosures: Nijland: Roche: Research Funding; Takeda: Research Funding; Genmab: Consultancy. Kersten: Adicet Bio: Honoraria; Takeda: Honoraria; Roche: Honoraria, Research Funding; Novartis: Honoraria; Miltenyi Biotech: Honoraria; Kite, a Gilead Company: Honoraria, Research Funding; BMS/Celgene: Honoraria, Research Funding. Chamuleau: Gilead: Research Funding; Roche: Honoraria; Genmab: Research Funding; BMS/Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria.

OffLabel Disclosure: Lenalidomide as immunomodulatory drug for patients with MYC-rearranged Diffuse Large B Cell Lymphoma

*signifies non-member of ASH