Scientific Reports: T cell count in peripheral blood for leukapheresis predicts response to subsequent CAR-T cell therapy

Predicting the response of chimeric antigen receptor (CAR)-T cell therapy is critical
to maximizing its therapeutic effectiveness against diffuse large B-cell lymphoma (DLBCL).
While several intrinsic risk factors for drug resistance and/or early recurrence have been identified, clinically useful markers to identify the potential activity of CAR-T cells have not been adequately studied
.
The properties of T cells during leukapheresis can serve as such a marker
.
Therefore, a research team evaluated the clinical effect
of peripheral blood CD3+ cell count on the clinical outcome of CAR-T cell therapy after leukapheresis.

A total of 44 patients with relapsed or refractory (r/r) DLBCL who received tisagen leclusel at Kyoto University Hospital were included
.
According to the CD3+ cell count, according to the analysis of the subject's operating characteristic curve, the patients were divided into CD3LOW group and CD3HIGH group
with a threshold of 553/μL.
The 1-year progression-free survival was significantly higher in the CD3HIGH group than in the CD3LOW group (68.
3% versus 17.
3%; Adjusted risk ratio [aHR], 0.
37; p = 0.
042）
。 Overall survival was also better in the CD3HIGH group (aHR, 0.
24; p = 0.
043）
。

Figure 1: Impact
of peripheral blood CD3 cell count on survival after leukapheresis.
Kaplan-Meier estimates progression-free survival (PFS)(A) and overall survival (OS)(B) based on the number of CD3 cells in leukapheresis.

Figure 2: Clinical course
of patients based on leukapheresis CD3 cell count.
The survival time (yellow bar) and survival time after progression (brown bar)
after CAR-T infusion in individual patients are shown.
Patients are divided into 2 groups (^high CD3⁺ and ^low CD3) based on CD3 cell count
at leukapheresis.
The green dots indicate the CD3 cell count
of the individual patient at leukapheresis.
The disease status [complete response (CR)/partial response (PR) or stable disease (SD)/progressive disease (PD)] is displayed at the bottom at the time
of infusion for each patient.
⁺⁺

<sup>Fig.
3: Correlation between lymphocyte count and CD3 cell count after CAR-T cell infusion by leukapheresis and its prognostic significance
.
Box plot showing lymphocyte count + low and high CD3 group patients (A)
on day 7 after CD3 infusion.
The scatterplot shows the correlation between peripheral blood CD3 cell count at leukapheresis and peripheral blood lymphocyte count on day 7 post-transfusion (B).

Kaplan-Meier estimated OS(C) based on the lymphocyte count (>1000/μL or ≤1000/μL)
on day 7.
+</sup>

In addition, higher CD3+ cell counts during leukapheresis were associated with significantly higher peripheral blood lymphocyte counts on day 7 post-CAR-T cell infusion (median 860 vs 420/μL, P = 0.
021), indicating that the transfused CAR-T cells expanded more widely in vivo
.

In conclusion, this study demonstrates that CD3+ cell counting in leukapheresis can predict the expansion of CAR-T cells after infusion and the outcome of CAR-T cell therapy, and helps to establish a comprehensive treatment strategy
at the time of leukapheresis.

Original source:

Wada, F.
, Jo, T.
, Arai, Y.
et al.
T-cell counts in peripheral blood at leukapheresis predict responses to subsequent CAR-T cell therapy.
Sci Rep12, 18696 (2022).
https://doi.
org/10.
1038/s41598-022-23589-9