【BLOOD】Outcome after failure of CD19 CART for aggressive B-cell lymphoma from the French DESCAR-T registry study

CD19 CAR T cell therapy is the mainstay of treatment in patients with relapsed/refractory sexually aggressive B-cell non-Hodgkin lymphoma (R/R invasive BCL
).

In the JULIET study, nearly 60% of patients progressed 6 months after CAR T cell infusion; The ZUMA 1 and TRANSCEND studies showed that about 50% of patients relapsed at 6 months; These data have also been confirmed
in multiple real-world studies.

The DESCAR-T registry study is a French national registry study designed by LYSA/LYSARC to collect real-world data
on commercial CAR-T cells (axi-cel and tisa-cel) within 15 years of CAR-T cell infusion.

Professor Catherine Thieblemont of France led the analysis of patient outcomes of progression/relapse of CAR T cells registered in DESCAR-T and determined the prognostic markers and treatment options after CAR-T in this population, and deeply studied the relationship between
treatment strategies at relapse and outcomes after CD19 CAR T failure.

fruit

patient

From August 2018 to April 12, 2021, the DESCAR-T registry study registered 680 consecutive patients with R/R invasive BCL, of which 550 received an infusion at the time of analysis and patients received axicabtagene-ciloleucel (axi-cel, n=350) or tisagenlecleucel (tisa-cel, n=200).

After a median follow-up of 7.

At the time of treatment/before the treatment was decided, most patients (n = 178, 74.

Of the 238 patients with relapse/disease progression after CAR T cell therapy, 54 patients (22.

Treatment and remission in case of CAR T failure

To further characterize treatment in patients with relapse/progression after CAR T cell therapy, the authors analyze subsequent treatments and types
.

Of the 154 patients with recurrence/progression after CAR T treatment, 120 (77.

Efficacy outcomes for different treatment types after failure of CAR T therapy

The authors further analyzed the response rate and survival outcomes after CAR-T recurrence and grouped treatments by category (Figure 1
).

The median PFS-2 after bispecific antibody, lenalidomide, targeted therapy, and immunochemotherapy was 3.

finale

In the overall patient population receiving CAR T cell therapy, the median PFS was 4.

For the 238 patients who failed, PFS-2 calculated since relapse/progression of CAR T cell infusion was 2.

The authors also analyzed PFS-2 and OS-2 for relapse/progression time after CAR T cell infusion based on CAR T treatment failure time: median PFS-2 was 1.

Prognostic factors

In the univariate model, factors significantly associated with PFS-2 deterioration include high LDH at infusion (p< 0.

Factors associated with poor OS-2 include high LDH (p< 0.
0001, HR=2.
66), ECOG PS≥2 (p=0.
0008, HR= 2.
37) during infusion, very early progression (D0-D30, p< 0.
0001, HR=2.
59), abnormal CRP and ferritin levels during infusion (CRP:p= 0.
0006, HR= 1.
05; ferritin: p= 0.
0002, HR= 1.
01); The type of treatment after CAR T also had no significant correlation with OS-2: bispecific antibodies (p=0.
2, HR=0.
51), lenalidomide (p=0.
06, HR=0.
60), targeted therapies (p=0.
7, HR=0.
91).

In multivariate analysis, factors associated with poor PFS-2 included high LDH at infusion (p< 0.
0001, HR= 3.
42) and abnormal ferritin levels during infusion (p= 0.
01, HR= 1.
02) (Table 3); There was no significant correlation between the type of therapy after CAR T and PFS-2: bispecific antibodies (p=0.
98, HR = not reached), lenalidomide (p=0.
07, HR=0.
55, with a tendency to improve), targeted therapies (p=0.
3, HR=0.
69).

The multivariate analysis of OS-2 identified the following factors associated with the poorer outcome (Table 3): high LDH (p= 0.
01, HR= 2.
10), elevated CRP (p= 0.
003, HR= 1.
11), and very early progression (D0-D30, p= 0.
0009, HR= 2.
93).

。 Some treatment types after CAR T were not significantly associated with OS-2: bispecific antibodies (p=0.
15, HR=0.
22) or targeted therapies (p=0.
078, HR=0.
47), but lenalidomide therapy was significantly associated with OS-2 optimization (p=0.
01, HR=0.
42).

discuss

CD19 CAR T cell therapy is an important breakthrough in R/R aggressive BCL therapy, but post-infusion failure is also common, with recurrence rates of up to 66%
in key clinical studies and real-world reports.
Features of patients at high risk of recurrence include total metabolic tumor volume, LDH, PS, CD19 status, etc.
, and properties of CAR T cell products such as kinetics, dose, and intrinsic factors in the tumor also have an impact
.

This DESCAR-T registry study confirmed that outcomes remain extremely poor in patients who fail after CAR T cell therapy, and even worse
if they fail within the first month.
Alternative therapeutic strategies (bispecific antibodies, lenalidomide) may improve PFS rates
in these patients.
Overall, patients with R/R invasive BCL who fail after CD-19 CAR T cell therapy still have unmet medical needs and further innovative strategies are needed to improve outcomes
in such patients.

References

Roberta Di Blasi,et al.
Outcomes of patients with aggressive B-Cell lymphoma after failure of anti-CD19 CAR T-Cell Therapy: A DESCAR-T analysis.
Blood .
2022 Sep 19; blood.
2022016945.
doi: 10.
1182/blood.
2022016945.

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