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

Abstract

SummaryDespite 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.

New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

“…Overall survival (OS) has improved significantly since the new therapy based on rituximab with cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) has been in use [130]. Nevertheless, refractoriness or relapse occur in one-third of patients, and most of them show poor long-term outcomes [131]. CXCR4 regulates tissue trophism of lymphoma cells and protects them from chemotherapy-induced apoptosis by promoting leukemic blasts homing into BM niches [132].…”

Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B‐cell non‐Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306)

“…Diffuse large B‐cell lymphoma (DLBCL) represents approximately 50% of NHL cases (Kane et al , ) and follicular lymphoma (FL) 20% (Bierman, ). For the ~30–40% patients who relapse or the 10% who are refractory to initial therapy (Gisselbrecht & Van Den Neste, ), salvage therapy followed by a high‐dose myeloablative regimen and stem cell transplant (SCT) is potentially curative (Tilly et al , ; National Comprehensive Cancer Network, ). However, many relapsed patients are ineligible for SCT because of comorbidities, advanced age or failure to respond to standard salvage regimens (Kuruvilla et al , ).…”

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas

“…Therapeutic outcomes may vary according to clinical behavior, whether indolent or aggressive, and patients may suffer various patterns of recurrence requiring subsequent lines of rescue therapies. Dismal prognosis still affects a significant fraction of patients with mature B-cell lymphomas, and new treatment strategies should be conceived to improve both objective response and survival (3)(4)(5)(6)(7)(8)(9).…”