Camrelizumab Plus Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin in Relapsed/Refractory Primary Mediastinal B-Cell Lymphoma: A Single-Arm, Open-Label, Phase II Trial

Clin Cancer Res. 2020 Sep 1;26(17):4521-4530. doi: 10.1158/1078-0432.CCR-20-0514. Epub 2020 Jun 4.

Abstract

Purpose: Patients with relapsed/refractory primary mediastinal B-cell lymphoma (rrPMBCL) represent a particularly challenging population to treat, with few life-saving treatment options in the context of a dismal prognosis.

Patients and methods: In this open-label, single-arm, phase II study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL. Patients received chemo-immunotherapy every 3 weeks until the second confirmed complete response (CR) or up to 12 cycles, followed by camrelizumab monotherapy for up to 1 year. The primary endpoints were objective response rate (ORR) and safety.

Results: Twenty-seven response evaluable patients were enrolled, who received a median of three first-line therapies, 59% with bulky disease. The ORR was 74%, including 56% with a CR. A median time of 1.7 months to response was observed, with 78% exhibiting tumor shrinkage at the first evaluation. After 24.8 months median follow-up, the median duration of response was not reached, with a 65% 2-year estimated response rate. Thirteen responders remained in sustained complete remission. Estimated 24-month progression-free survival and overall survival rates were 48.2% and 81.5%, respectively. Any grade and grade 3 treatment-related adverse events (AE) occurred in 93% and 33% of patients, respectively; with no grade 4 or 5 AEs. Baseline levels of IL10, IFNγ, and soluble Fas were associated with objective response.

Conclusions: Camrelizumab plus GVD chemotherapy offers a potent option as life-saving chemo-immunotherapy with promising efficacy and a manageable safety profile for patients with rrPMBCL, especially with bulky aggressive disease.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Biomarkers, Tumor / blood
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Lymphoma, B-Cell / blood
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / pathology
  • Male
  • Mediastinal Neoplasms / blood
  • Mediastinal Neoplasms / drug therapy*
  • Mediastinal Neoplasms / mortality
  • Mediastinal Neoplasms / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Prognosis
  • Progression-Free Survival
  • Vinorelbine / administration & dosage
  • Vinorelbine / adverse effects
  • Young Adult
  • fas Receptor / blood

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • FAS protein, human
  • IFNG protein, human
  • IL10 protein, human
  • fas Receptor
  • liposomal doxorubicin
  • Interleukin-10
  • Polyethylene Glycols
  • camrelizumab
  • Doxorubicin
  • Interferon-gamma
  • Vinorelbine