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Clinical Trial
. 2023 Aug 8;7(15):3968-3977.
doi: 10.1182/bloodadvances.2022008888.

Central nervous system relapse in younger patients with diffuse large B-cell lymphoma: a LYSA and GLA/DSHNHL analysis

Catherine Thieblemont  1 , Bettina Altmann  2 , Fabian Frontzek  3 , Loïc Renaud  1 , Loic Chartier  4 , Nicolas Ketterer  5 , Christian Récher  6 , Viola Poeschel  7 , Olivier Fitoussi  8 , Gerhard Held  9 , Olivier Casasnovas  10 , Corinne Haioun  11 , Franck Morschhauser  12 , Bertram Glass  13 , Nicolas Mounier  14 , Herve Tilly  15 , Andreas Rosenwald  16 , German Ott  17 , Georg Lenz  3 , Thierry Molina  18 , Marita Ziepert  2 , Norbert Schmitz  3
Affiliations
Clinical Trial

Central nervous system relapse in younger patients with diffuse large B-cell lymphoma: a LYSA and GLA/DSHNHL analysis

Catherine Thieblemont et al. Blood Adv. .

Abstract

Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients with progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in frontline therapy has not been systematically investigated in this context. To this end, we analyzed a large cohort of 2203 younger patients with DLBCL treated on 10 German (German Lymphoma Alliance [GLA]/The German High Grade Non-Hodgkin's Lymphoma Study Group [DSHNHL]) and French (The Lymphoma Study Association [LYSA]) prospective phase 2 and 3 trials after first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone) followed by consolidation including multiple drugs crossing the blood-brain barrier (BBB). Patients with DLBCL with an age-adjusted International Prognostic Index (aaIPI) of 0 to 1 showed very low cumulative incidence rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year cumulative incidences 0%-1%). Younger high-risk patients with aaIPI of 2 to 3 had 3-year cumulative incidence rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (hazard ratio 2.4; 95% confidence interval: 0.8-7.4; P = .118). Thus, for younger high-risk patients, frontline regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.

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Conflict of interest statement

Conflict-of-interest disclosure: C.T. received honoraria from Roche, Amgen, Janssen, Celgene, and Gilead Science/Kyte Beigene; is in a consulting/advisory role for Roche, Gilead Sciences, Janssen, Celgene, Novartis, BeiGene, and Bristol Myers Squibb (BMS)/Celgene; and received research funding, travel, and accommodations expenses from Roche and Novartis outside the submitted work. C.R. received research grants from AbbVie, Amgen, Novartis, BMS-Celgene, Jazz Pharmaceuticals, Agios, Chugai, MaaT Pharma, Astellas, Roche, Daiichi-Sankyo, and IQVIA, and is an adviser for AbbVie, Janssen, Jazz Pharmaceuticals, Novartis, Celgene, Otsuka, Astellas, Daiichi-Sankyo, Macrogenics, Pfizer, Roche, Servier, and Takeda. V.P. received travel support from AbbVie, Amgen, BMS, Gilead, and Roche. O.S. received research funding from Roche, Takeda, and Gilead, and is on the advisory board of and received honoraria from Celgene, Roche, Takeda, Gilead, BMS, Merck, AbbVie, and Janssen outside the submitted work. F.M. received research funding from Roche, Takeda, and Gilead, and is on the advisory board of and received honoraria from Celgene, Roche, Takeda, Gilead, BMS, Merck, AbbVie, and Janssen outside the submitted work. H.T. is on the advisory board of and received honoraria from Roche. G.L. received research funding from AstraZeneca, Agios, Aquinox, Bayer, Celgene, Gilead, Janssen, Morphosys, Novartis, Roche, and Verastem, and received honoraria from ADC Therapeutics, AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Constellation, Genmab, Gilead, Incyte, Janssen, Karyopharm, Miltenyi, Morphosys, NanoString, Novartis, and Roche. N.S. received research funding from Janssen and received honoraria from Riemser/Esteve, Takeda, Kite/Gilead, and Novartis outside the submitted work. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Survival analysis. PFS (A,C,E) and OS (B,D,F) for patients with aaIPI of 0 without bulk (A-B), aaIPI of 1 (C-D), and aaIPI of 2 to 3 (E-F) according to first-line therapy (R-ACVBP vs R-CHO(E)P). Log-rank P values are presented.
Figure 2.
Figure 2.
Cumulative incidence of CNS relapse for patients with aaIPI of 2 to 3 according to first-line therapy (R-ACVBP vs R-CHO[E]P). Adjusted hazard ratio (HR) with 95% CI is presented.
Figure 3.
Figure 3.
OS of young patients with DLBCL after CNS event (n = 40).
See this image and copyright information in PMC

References

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