Clinicopathological analysis of primary refractory diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy

Cancer Med. 2021 Aug;10(15):5101-5109. doi: 10.1002/cam4.4062. Epub 2021 Jun 9.

Abstract

Background: Approximately 15% of patients with diffuse large B-cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab-containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL.

Methods: Sixty-nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R-CHOP] or relapse within 6 months of R-CHOP) (n = 41) or primary progressors (no response to R-CHOP) (n = 28). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test.

Results: At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non-germinal center B-cell-like type DLBCL, and 42% had double-expressor lymphoma (MYC and BCL2 expression). The 3-year overall survival rate was significantly poorer in the primary progressors group than in the partial responders' group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC-ASCT were primary progressors; only one patient survived without relapse. Although double-expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC-ASCT-treated patients (p = 0.002).

Conclusions: We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunotherapy / methods
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Recurrence
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Salvage Therapy / methods
  • Survival Rate
  • Treatment Outcome
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • BCL2 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone