Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma

Cancer Med. 2020 Aug;9(16):5827-5838. doi: 10.1002/cam4.3259. Epub 2020 Jul 1.


Purpose: Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti-CD19 and anti-CD20 CAR-T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity.

Methods: Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti-CD19 and anti-CD20 CAR-T cells. Treatment response, toxicity, and persistence were monitored continuously.

Results: Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%-94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%-74.3%) had a complete response (CR). Peak levels of anti-CD19 and anti-CD20 CAR cells were associated with response (P = .007 and .002). Grade 3-4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression-free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level.

Conclusions: Coadministration of anti-CD19 and CD20 CAR-T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at as NCT03207178.

Keywords: CAR-T; CD19; CD20; DLBCL; clinical trial.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anemia / etiology
  • Antigens, CD19*
  • Antigens, CD20*
  • Antineoplastic Agents / therapeutic use
  • B-Lymphocytes
  • CD4-CD8 Ratio
  • Confidence Intervals
  • Cyclophosphamide / therapeutic use
  • Cytokine Release Syndrome / etiology
  • Female
  • Glycolysis
  • Humans
  • Ifosfamide / therapeutic use
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / therapy*
  • Male
  • Middle Aged
  • Neutropenia / etiology
  • Progression-Free Survival
  • Receptors, Chimeric Antigen / therapeutic use*
  • Recurrence
  • T-Lymphocytes / transplantation*
  • Thrombocytopenia / etiology
  • Time Factors
  • Transplantation Conditioning / methods
  • Treatment Outcome
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Young Adult


  • Antigens, CD19
  • Antigens, CD20
  • Antineoplastic Agents
  • CD19 molecule, human
  • Receptors, Chimeric Antigen
  • Cyclophosphamide
  • Vidarabine
  • fludarabine
  • Ifosfamide

Associated data