How I manage patients with relapsed/refractory diffuse large B cell lymphoma

Abstract

Despite progress in the upfront treatment of diffuse large B cell lymphoma (DLBCL), patients still experience relapses. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory (R/R) DLBCL. However, half of the patients will not be eligible for transplantation due to ineffective salvage treatment, and the other half will relapse after ASCT. In randomized studies, no salvage chemotherapy regimen is superior to another. The outcomes are affected by the secondary International Prognostic Index at relapse and various biological factors. The strategy is less clear in patients who require third-line treatment. A multicohort retrospective non-Hodgkin lymphoma research (SCHOLAR-1) study conducted in 636 patients with refractory DLBCL showed an objective response rate of 26% (complete response 7%) to the next line of therapy with a median overall survival of 6·3 months. In the case of a response followed by transplantation, long-term survival can be achieved in DLBCL patients. There is clearly a need for new drugs that improve salvage efficacy. Encouraging results have been reported with chimeric antigen receptor -T cell engineering, warranting further studies in a well-defined control group of refractory patients. The Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) was used as a handy framework to build the discussion.

Keywords: CAR-T cells; HSC transplantation; cellular therapies; chemotherapy; refractory/relapsed DLBCL.

Figure 1

Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study: main results (Gisselbrecht et al, 2010, 2012). ASCT, autologous stem cell transplantation; BEAM, carmustine, etoposide, cytarabine, melphalan; DLBCL, diffuse large B cell lymphoma; EFS, event‐free survival; OS, overall survival; PR, partial response; CR, complete response; R‐DHAP, rituximab‐dexamethasone, cytarabine, cisplatin; R‐ICE, rituximab‐ifosfamide, etoposide, carboplatin.