Clinical heterogeneity of diffuse large B cell lymphoma following failure of front‐line immunochemotherapy

Abstract

Summary This study aimed to describe the patterns of care and outcomes of diffuse large B cell lymphoma (DLBCL) after failure of front line anthracycline-based immunochemotherapy (IC). Patients with newly diagnosed lymphoma were prospectively enrolled in Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence. All DLBCL and primary mediastinal B-cell lymphoma (PMBL) patients treated with front-line anthracycline-based IC were followed for relapse. Patients with relapse on follow-up and subsequently retreated were included in this analysis. 1039 patients received anthracycline-based IC between 2002 and 2012, of which 244 relapsed and were subsequently retreated. Across all therapies, overall survival at 4 years (OS4) from relapse was 28% and 103 patients ultimately underwent autologous haematopoietic cell transplant (autoHCT) with OS4 from autoHCT of 51%. Patients relapsing after 12 months from initial diagnosis had OS4 of 47% but those with a transient or no response to initial therapy had OS4 of only 13%. Outcomes of relapsed or refractory DLBCL differ substantially when categorized by response to initial therapy, timing of relapse and opportunity to undergo autoHCT. The design and interpretation of uncontrolled trials should account for this heterogeneity in patients with relapsed DLBCL.

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

“…Hamadani et al reported that patients with an early relapse had shorter OS than patients with a primary refractory disease who were treated with ASCT (2‐year OS 59% vs 41%). By contrast, 3 recent reports showed that patients with an early relapse had better OS than patients with a primary refractory disease . In our report, these 2 subgroups of refractory patients had comparable outcomes.…”

“…Therefore, only half of the patients for whom an ASCT is planned present with a chemosensitive disease and ultimately receive an ASCT, yielding a 4‐year overall survival (OS) of 60% to 65% . Furthermore, previous studies have shown that patients with refractory disease have worse outcomes than patients who relapse 1 year after diagnosis . The precise definition of refractoriness can vary between studies, and analyzing the outcomes of patients according to initial chemo‐sensitivity (complete response (CR), partial response (PR), or progression during first‐line treatment) is somewhat controversial .…”

“…Furthermore, previous studies have shown that patients with refractory disease have worse outcomes than patients who relapse 1 year after diagnosis . The precise definition of refractoriness can vary between studies, and analyzing the outcomes of patients according to initial chemo‐sensitivity (complete response (CR), partial response (PR), or progression during first‐line treatment) is somewhat controversial . Recent reports have shown that patients who exhibit a PR after first‐line Immuno‐chemotherapy have a longer OS than patients who have a primary refractory disease, but the OS was still shorter among those patients than among patients with a CR …”

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)

“…Furthermore, patients with primary refractory disease were excluded and approximately two‐thirds of patients in both arms had relapsed ≥1 year after first‐line treatment initiation. Both primary refractory disease and early relapse are associated with poor prognosis (Farooq et al , ).…”

FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma

“…Although standard chemoimmunotherapy is considered curative for more than half of all patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), an estimated 20% to 30% relapse after an initial remission, and an estimated 10% of patients have primary refractory disease (1,2). High-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) is the usual standard for first relapse of DLBCL, provided that the relapse is chemosensitive, and can cure a subset of patients.…”