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Multicenter Study
. 2024 Jul 9;8(13):3402-3415.
doi: 10.1182/bloodadvances.2024012760.

Defining primary refractory large B-cell lymphoma

Allison M Bock  1   2 , Raphael Mwangi  3 , Yucai Wang  1 , Arushi Khurana  1 , Matthew J Maurer  3 , Amy Ayers  4 , Brad S Kahl  5 , Peter Martin  6 , Jonathon B Cohen  7 , Carla Casulo  8 , Izidore S Lossos  9 , Umar Farooq  10 , Sabarish Ayyappan  10 , Tanner Reicks  3 , Thomas M Habermann  1 , Thomas E Witzig  1 , Christopher R Flowers  4 , James R Cerhan  2 , Loretta J Nastoupil  4 , Grzegorz S Nowakowski  1
Affiliations
Multicenter Study

Defining primary refractory large B-cell lymphoma

Allison M Bock et al. Blood Adv. .

Abstract

Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort. Patients with newly diagnosed LBCL were enrolled in the Molecular Epidemiological Resource cohort (MER; N = 949) or the Lymphoma Epidemiology of Outcomes cohort (LEO; N = 2755) from September 2002 to May 2021. Primary refractory LBCL was defined as no response (stable disease [SD]) or progressive disease (PD) during, or by the end of, frontline (1L) IC (primary PD; PPD); partial response at end of treatment (EOT PR); or relapse within 3 to 12 months after achieving CR at EOT to 1L IC (early relapse). In the MER cohort, patients with PPD had inferior overall survival (OS; 2-year OS rate: 15% MER, 31% LEO) when compared with other subgroups considered in defining primary refractory disease, EOT PR (2-year OS rate: 38% MER, 50% LEO) and early relapse (2-year OS rate: 44% MER, 58% LEO). Among patients receiving 1L IC with curative intent, we identified that patients with PPD are the key subgroup with poor outcomes. We propose a definition of primary refractory LBCL as SD or PD during, or by the end of, 1L treatment.

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Conflict of interest statement

Conflict-of-interest disclosure: A.M.B. reports consultancy or advisory role with AbbVie; and reports honoraria from Primum. Y.W. reports employment or leadership position with Merck (immediate family member); reports consultant or advisory role with Loxo, Incyte, Innocare, TG Therapeutics, Kite (a Gilead company), Lilly, Janssen, and BeiGene; reports stock ownership in Merck (immediate family member); received honoraria from Kite (a Gilead company); received research funding from InnoCare, Incyte, Novartis, Genentech, Loxo, MorphoSys, and Genmab. M.J.M. reports employment or leadership position with Exact Sciences (immediate family member); reports consultant or advisory role with Genmab and Adpative Biotechnologies; reports stock ownership in Exact Sciences (immediate family member); and received research funding from MorphoSys, Bristol Myers Squibb, Roche/Genentech, and Genmab. B.S.K. declares consultant or advisory role with Celgene, AbbVie, Pharmacyclics, Acerta Pharma, ADC Therapeutics, Genentech, Roche, AstraZeneca, BeiGene, Bayer, MEI Pharma, Kite/Gilead, MorphoSys, Janssen, Celgene, Incyte, and Genmab; and received research funding from Genentech, Acerta Pharma, ADC Therapeutics, and Celgene. P.M. reports consultant or advisory role with Janssen, BeiGene, Karyopharm Therapeutics, Kite/Gilead, Verastem, ADC Therapeutics, Bristol Myers Squibb/Celgene, Epizyme, Merck, MorphoSys, and Takeda; and received research funding from Karyopharm Therapeutics. J.B.C. reports consultant or advisory role with AbbVie, Janssen, Loxo, Kite/Gilead, AstraZeneca, Aptitude Medical, Adicet Bio, and Adaptive Biotechnologies; received research funding from Celgene, Janssen, Novartis, Takeda, AI Therapeutics, Genentech, American Society of Hematology, Lymphoma Research Foundation, Loxo, BioInvent, and AstraZeneca. C.C. reports consultant or advisory role with AbbVie; and received research funding from Gilead, SecuraBio, Genmab, and Genentech. I.S.L. reports consultant or advisory role with Janssen, Seagen, and Verastem; received honoraria from Janssen; and received research funding from the National Cancer Institute. U.F. reports consultant or advisory role with MorphoSys and Caribou; and received honoraria from Kite Pharma and Caribou. T.M.H. reports consultant or advisory role with Celgene, Kite/Gilead; received research funding from Genentech; received other remuneration/uncompensated from Tess Therapeutics, Loxo/Lilly, MorphoSys, Incyte, and BeiGene. C.R.F. and J.R.C. report consultant or advisory roles with Bristol Myers Squibb and Protagonist Therapeutics; received research funding from NanoString Technologies, Celgene, Genentech, and Genmab; and received other remuneration/uncompensated from Regeneron. L.J.N. reports a consultant or advisory role with Interius Biotherapeutics and SIRPant Immunotherapeutics; received honoraria from ADC Therapeutics, Bristol Myers Squibb, Caribou Biosciences, Epizyme, Genentech/Roche, Genmab, Gilead Sciences, Janssen Oncology, MorphoSys, Novartis, Takeda, and TG Therapeutics; and received research funding from Allogene Therapeutics, Bristol Myers Squibb/Celgene, Caribou Biosciences, Epizyme, Genentech/Roche, Gilead Sciences, IgM Biosciences, Janssen Biotech, Novartis, and Takeda. G.S.N. reports a consultant or advisory role for Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead, TG Therapeutics, Kymera, Karyopharm Therapeutics, Ryvu Therapeutics, and Bantham; and received research funding from Celgene, NanoString Technologies, and MorphoSys.

The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS from time of relapse based on timing of refractory status. (A and B) OS in MER cohort; and (C and D) OS in LEO cohort.
Figure 2.
Figure 2.
OS for PPD compared with all other patients with newly diagnosed LBCL in the LEO cohort. OS from date of last treatment (nonrelapsed patients) or date of relapse/progression (relapsed patients).
See this image and copyright information in PMC

References

    1. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–242. - PubMed
    1. Pfreundschuh M, Trümper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379–391. - PubMed
    1. Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121–3127. - PubMed
    1. Hitz F, Connors JM, Gascoyne RD, et al. Outcome of patients with primary refractory diffuse large B cell lymphoma after R-CHOP treatment. Ann Hematol. 2015;94(11):1839–1843. - PubMed
    1. Farooq U, Maurer MJ, Thompson CA, et al. Clinical heterogeneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy. Br J Haematol. 2017;179(1):50–60. - PMC - PubMed

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