Refractory diffuse large B-cell lymphoma after first-line immuno-CT: Treatment options and outcomes

Lauriane Filliatre-Clement; Delphine Maucort-Boulch; Estelle Bourbon; Lionel Karlin; Violaine Safar; Emmanuel Bachy; Pierre Sesques; Emmanuelle Ferrant; Fadela Bouafia; Anne Lazareth; Dana Ghergus; Bertrand Coiffier; Alexandra Traverse Glehen; Gilles Salles; Hervé Ghesquieres; Clémentine Sarkozy

doi:10.1002/hon.2512

Refractory diffuse large B-cell lymphoma after first-line immuno-CT: Treatment options and outcomes

Hematol Oncol. 2018 May 2. doi: 10.1002/hon.2512. Online ahead of print.

Authors

Lauriane Filliatre-Clement^{1

2}, Delphine Maucort-Boulch^{3

4

5}, Estelle Bourbon¹, Lionel Karlin¹, Violaine Safar¹, Emmanuel Bachy^{1

6}, Pierre Sesques¹, Emmanuelle Ferrant¹, Fadela Bouafia¹, Anne Lazareth¹, Dana Ghergus¹, Bertrand Coiffier^{1

6}, Alexandra Traverse Glehen^{1

6}, Gilles Salles^{1

6}, Hervé Ghesquieres^{1

6}, Clémentine Sarkozy^{1

6}

Affiliations

¹ Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service d'Hématologie, Pierre Bénite Cedex, France.
² Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France.
³ Service de Biostatistique-Bioinformatique, Hospices Civils de Lyon, Lyon, France.
⁴ Université Lyon 1, Villeurbanne, France.
⁵ CNRS UMR 5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France.
⁶ INSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Lyon-1, Pierre Bénite Cedex, France.

PMID: 29722049
DOI: 10.1002/hon.2512

Abstract

In the rituximab era, one-third of diffuse large B-cell lymphoma patients experience relapse/refractory disease after first-line anthracycline-based immunochemotherapy. Optimal management remains an unmet medical need. The aim of this study was to report the outcomes of a cohort of refractory patients according to their patterns of refractoriness and the type of salvage option. We performed a retrospective analysis, which included 104 diffuse large B-cell lymphoma patients treated at Lyon Sud University Hospital (2002-2017) who presented with refractory disease. Refractoriness was defined as progressive/stable disease during first-line treatment (primary refractory, N = 47), a partial response after the end of first-line treatment that required subsequent treatment (residual disease, N = 19), or relapse within 1 year of diagnosis after an initial complete response (CR) (early relapse, N = 38). The 2-year overall survival (OS) rates for primary refractory, early relapse, and residual disease patients were 27%, 25%, and 52%, respectively, while the event-free survival rates for those groups were 13%, 13%, and 42%, respectively. In a univariate analysis, lactate dehydrogenase level, Ann Arbor stage, poor performance status, high age-adjusted International Prognostic Index score, and age > 65 years were associated with shorter OS. The use of rituximab and platinum-based chemo during the first salvage treatment was associated with prolonged OS. In a multivariate analysis, age (HR:2.06) and rituximab use (HR:0.54) were associated with OS. Among patients <65 years who achieved a CR, autologous stem-cell transplant was associated with higher 2-year OS (90% vs 74%, P = 0.10). Patients who were treated with a targeted therapy in the context of a clinical trial after second-line treatment had a higher 2-year OS (34% vs 19%, P = 0.06). In conclusion, patients with primary refractory disease or early relapse have very poor outcomes but may benefit from rituximab retreatment during the first salvage treatment.

Keywords: diffuse large B-cell lymphoma; refractory; rituximab.