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

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.

Commercial anti‐CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center

“…2 Refractory/relapsed (R/R) patients usually have a very poor outcome. [3][4][5] Initially approved for R/R acute lymphoblastic leukemia (ALL) in pediatric and young adult patients in April 2017 in the USA, 6,7 tisa-cel was subsequently approved for the treatment of R/R DLBCL and transformed follicular lymphoma (trFL) after 2 or more lines of systemic therapy in August 2018 in Europe. Likewise, axi-cel was approved in August 2018 for R/R DLBCL, trFL and primary mediastinal B cell lymphoma (PMBCL) after two or more lines of systemic therapy in Europe.…”

“…Although the majority of patients are cured with first‐line immunochemotherapy, 10% to 15% have primary refractory disease, and another 20% to 35% ultimately experience relapse 2 . Refractory/relapsed (R/R) patients usually have a very poor outcome 3‐5 …”

A LYSA Phase Ib Study of Tazemetostat (EPZ-6438) plus R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) with Poor Prognosis Features

“…Age-adjusted IPI (aaIPI), a derivative of the IPI score based on lactate dehydrogenase (LDH), stage, and ECOG performance status, can stratify the patients at diagnosis and predicts outcome (3). In patients older than 60 years, DLBCL can be cured in 50% to 60% of the cases following first-line R-CHOP (4-6) and 30% to 40% will present a R-CHOP primary refractory or an early-relapse disease (7,8). Those "poor responders" to R-CHOP have a 1-year overall survival (OS) of less than 20% and still represent a group of patients with a clear unmet medical need (7).…”

Autologous Hematopoietic Stem Cell Transplantation is an Effective Treatment Option in Early Relapsed and Primary Refractory Diffuse Large B-Cell Lymphoma.

“…The response was evaluated by CT. 4 Responses to second line in a French retrospective study with 104 patients were CR 23%, with 77% patients receiving Rituximab in salvage regimens. 13 The NCIC-CTG LY.12 study showed a CR of 13.8% for GDP and 14.6% for DHAP in a population with 71% primary refractory or relapsed within 1 year. In this study, the response was also evaluated by CT. 5 Compared to these results, our patients achieved slightly higher rates of response to second line treatment.…”