Researchers utilized a strategy of early lymphopheresis in a study aimed at optimizing CD19-based chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Results were reported in the British Journal of Haematology.
In this prospective analysis, the investigators evaluated clinical outcomes in patients receiving CD19-based CAR-T treatment for DLBCL using either early lymphopheresis (early group) or standard lymphopheresis (standard group).
Early lymphopheresis in this study occurred at first relapse prior to salvage treatment, while standard lymphopheresis occurred at the second relapse or later. Patients in the early group had primary refractory DLBCL or had experienced failure of first-line therapy within 1 year, while patients assigned to the standard group had received at least 2 lines of therapy.
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There were 22 patients in the early group and 23 patients in the standard group, and patients had a median age of 69 years in each group. The early group had received a median of 1 line of prior therapy, while the standard group had received a median of 3 prior lines of therapy (range, 2-7).
The early group showed a higher percentage of naïve T cells and greater in vitro T-cell functionality. Percentages of both CD4+ Tnaïve cells (P =.016) and CD8+ Tnaïve cells (P =.018) were significantly lower in the standard group than in the early group.
The percent of activated T cells of both CD4+ and CD8+ subpopulations in peripheral blood mononuclear cells was also significantly lower in the standard group than in patients of the early group (P =.011 for CD4+ T cells and P =.009 for CD8+ T cells). Multiple other observations regarding functionality and T-cell differentiation characteristics were also reported.
The early group showed less evidence of T-cell exhaustion, compared with the standard group, based on the markers PD-1, LAG-3, and Tim-3. Tim-3 expression either trended higher or was significantly higher in the standard group than the early group in CD4+ (P =.065) and CD8+ (P =.001) T-cell subpopulations. The standard group also showed significantly higher PD-1 expression on CD8+ T cells (P =.014) and higher LAG-3 expression on CD4+ T cells (P =.010).
Regarding clinical outcomes, there were not significant differences observed in progression-free survival (PFS) or overall survival (OS) between the groups. However, the overall response rate was significantly higher, at 60%, for the early group than for the standard group, in which it was 35% (P <.0001).
The median PFS durations were 74 days for the early group and 52 days for the standard group (hazard ratio [HR], 0.63; 95% CI, 0.255-1.572). Median OS was not reached in the early group, compared with 263 days after infusion for the standard group (HR, 0.521; 95% CI, 0.18-1.51).
“Our observations underline the multifactorial parameters involved in successful response to CART therapy, further strengthening the notion that the features of CART final product are influenced not only by the patient’s intrinsic characteristics, but also by the manufacturing process,” the investigators wrote in their report.
Reference
Dubnikov Sharon T, Assayag M, Avni B, et al. Early lymphocyte collection for anti-CD19 CART production improves T-cell fitness in patients with relapsed/refractory diffuse large B-cell lymphoma. Br J Haematol. Published online April 18, 2023. doi:10.1111/bjh.18816
