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Nivolumab with CAR T-cell therapy in progressive DLBCL: final analysis of a phase II study

May 8, 2024
Learning objective: After reading this article, learners will be able to cite a new development in the treatment of diffuse large B-cell lymphoma.

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Chimeric antigen receptor (CAR) T-cell therapy can improve outcomes for patients with diffuse large B-cell lymphoma (DLBCL); however, patients with rapid progressive disease at lymphodepletion have poor outcomes.1 The addition of checkpoint inhibitors targeting PD-1 to CAR T-cell therapy may improve outcomes in patients with DLBCL.1

During the 50th Annual Meeting of the EBMT, Amit presented final results from a phase II trial (NCT05385263) investigating the addition of nivolumab, a checkpoint inhibitor targeting PD-1, to CAR T-cell therapy in patients with DLBCL with progressive disease.1 Below, we summarize the key findings.

Study design1,2

  • This study included patients with DLBCL with progressive disease who were enrolled in a CAR T-cell therapy trial.
  • Patients received the first dose of nivolumab on Day 5 after CAR T-cell infusion.
    • Patients with <100 CAR T cells/μL on Day 7 received a second dose of nivolumab on Day 19.
  • Endpoints included safety, response, and durability of response.

Key findings1

Patient characteristics

  • In total, 20 patients were included in this trial, of which 12 patients were eligible for nivolumab treatment.
    • Eight patients were not eligible to receive nivolumab due to ongoing toxicity following CAR T-cell therapy.
  • The median age was 67 years (range, 40–79).
  • In total, 95% of patients had progressive disease at lymphodepletion.


In the nivolumab group, 50% of patients experienced post-nivolumab cytokine-release syndrome (Table 1).

Table 1. Toxicity profile*

Domain, %

All patients (n = 20)

Patients receiving nivolumab (n = 12)

Patients’ ineligible for nivolumab (n = 8)

Overall CRS




Grade 3–4 CRS




Overall ICANS




Grade 3–4 ICANS




Post nivolumab CRS/ICANS




Grade 3–4 ICAHT









Overall IEC-HS




Grade 3–4 IEC-HS




Patients with infections by 3 months




Patients with IgG <3.5 gr/L




NRM at 1 month




CRS, cytokine release syndrome; ICAHT, immune effector cell–associated hematotoxicity; ICANS, immune effector cell associated neurotoxicity syndrome; IEC-HS, immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome; IgG, immunoglobulin G; NRM, non-relapse mortality.
*Adapted from Amit1

All Grade 1–2 CRS.


  • At 1-month post-CAR T-cell infusion, in all patients, the overall response and complete response rates were 84% and 53%, respectively.
    • Response rates were similar between patients who received nivolumab treatment and those who were ineligible due to ongoing toxicities.

Survival outcomes

  • There were no major differences in the survival outcomes between patients who received nivolumab vs those who were ineligible for nivolumab.
  • The 6- and 12-month survival outcomes for all patients are shown in Figure 1.

Figure 1. 6- and 12-month progression-free survival and overall survival rates* 

*Data from Amit1


  • Patterns of expansion as assessed by quantitative polymerase chain reaction and area under the curve showed no difference between treatment groups.
  • There were no differences in CAR-T cell subtypes and the percentage of activation/inhibitory markers in the infused product between treatment groups.
    • CAR T-cell subtypes in the peripheral blood at Day 7 were also similar between treatment groups.
  • Within the nivolumab group, PD-1 expression was significantly decreased in all mononuclear cells (p = 0.001), in CAR T-cells (p = 0.0034), and in CD3+ non-CAR T-cells (n = 0.001) when compared with patients who did not receive nivolumab.
  • CD8+/CD45RO−/CD27+ cells were enriched in both CAR T-cells and CD3+ cells in patients who received nivolumab.
Key learnings
  • The addition of nivolumab to CAR T-cell therapy was relatively well tolerated; however, some patients were ineligible to receive nivolumab due to CAR T-cell toxicities.
  • The addition of nivolumab demonstrated favorable efficacy compared with historical controls of patients with progressive DLBCL; however, durability of response was suboptimal.
  • Nivolumab treatment increased the number of CD8+/CD45RO−/CD27+ cells which may promote CAR T-cells and bystander lymphocytes to improve efficacy.

  1. Amit O. Addition of nivolumab tailored by expansion of CAR-T cells in patients with progressive DLBCL at lymphodepletion – A phase 2, prospective interventional study – final analysis. Oral abstract #GS02–09. 50th Annual Meeting of the EBMT; Apr 15, 2024. Glasgow, UK.
  2. Ram R, Amit O, Perry C, et al. Addition of nivolumab tailored by expansion of CAR-T cells in patients with progressive DLBCL at lymphodepletion – A phase 2, prospective interventional study – final analysis. Abstract #GS02-07. 50th Annual Meeting of the EBMT; Apr 15, 2024. Glasgow, UK.

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