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Results from the French DESCAR-T registry study: Use of cancer databases for the management of data from patients undergoing CAR-T cell therapy for the treatment of DLBCL

Aug 14, 2021
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Patients with B-cell acute lymphoblastic leukemia (B-ALL) or diffuse large B-cell lymphoma (DLBCL) with refractory or relapsed (R/R) disease can face poor clinical outcomes and reduced survival. CAR-T cell therapy with tisagenlecleucel (tisa-cel) or axicabtagene ciloleucel (axi-cel) has been shown to improve long-term outcomes for these patients. Following successful clinical trials, long-term safety and efficacy data, pharmacovigilance, and real-word data are needed to inform patient safety and the long-term use and future health economics of CAR T-cell therapy.

Steven Le Gouill presented the first results from patients with DLBCL treated with CAR T-cell therapy and enrolled in the DESCAR-T registry, at the 17th International Conference on Malignant Lymphoma (17-ICML).1 Here we summarize the work of Steven Le Gouill and colleagues,1 describing real-world results from the French national registry of patients with hematologic malignancies treated with CAR-T cell therapy, focusing on patients with DLBCL.

Study design

DESCAR-T is the French national registry for patients with DLBCL and ALL treated with CAR T-cell therapy. All patients with DLBCL registered in DESCAR-T between December 2019 and April 2021 were eligible for the study; DESCAR-T, currently, has 19 enrolling sites.

The main outcomes were clinical outcomes, including overall response rate (ORR), complete remission (CR), progressive disease (PD), overall survival (OS), progression-free survival (PFS), and duration of response (DOR), as well as safety outcomes.

Results

647 patients with DLBCL were enrolled:

  • CAR-T was ordered in 607 patients:
    • CAR-T was not ordered in 10 patients for varying reasons, including patient outside of inclusion or exclusion criteria, patient refusal, infection, disease progression, and death.
    • Thirty patients are ongoing, five of whom have completed leukapheresis and 25 of whom are pending leukapheresis.
  • Of the 607 patients for whom CAR-T was ordered, 550 were treated:
    •  Of the 57 patients for whom CAR-T was ordered but not administered, four patients are ongoing, and 53 were not administered CAR-T due to various reasons (including disease progression, leukapheresis failure, physician decision, and death before administration).
    • Of the 550 patients who were treated, 200 received tisa-cel and 350 received axi-cel.

Key clinical data for the 550 patients who received CAR-T cell therapy, including demographic and diagnostic data, can be seen in Table 1.

Table 1. Clinical and demographic data for CAR-T treated patients*

Parameter

Result

Male/female

331/219

Median age at CAR-T order, years (range)

63 (18−79)

Diagnosis at registration, %

              DLBCL, NOS

90

              PMBL

4

              HGBL

1.7

              Others/missing

4.3

Median lines of treatment (range)

3 (1−10)

Prior auto-SCT, %

22.5

Prior allo-SCT, %

2

Median days from CAR-T order to TTT (IQR)

50 (43−60)

allo-SCT, allogeneic stem cell transplant; auto-SCT, autologous stem cell transplant; CAR-T, chimeric antigen receptor T-cell therapy; DLBCL, diffuse large B-cell lymphoma; HGBL, high-grade B-cell lymphoma; IQR, interquartile range; NOS, not otherwise specified; PMBL, primary mediastinal B-cell lymphoma; TTT, time to treatment.
*Adapted from Le Gouill et al.1

Safety data and adverse events

Data on specific toxicities experienced within 10 days of receiving CAR-T cell therapy were available in 515 patients and can be seen in Table 2, along with treatments for toxicities.

Table 2. CAR-T related adverse events*

Toxicity, %

All patients
(n = 515)

Axi-cel
(n = 322)

Tisa-cel
(n = 193)

Cytokine release syndrome

              All grades

81.2

85.7

73.6

              Grade ≥3

85

9.3

7.3

Neurotoxicity

              All grades

35.7

45.7

19.2

              Grade ≥3

9.7

14.5

1.6

Medically significant/opportunistic infection

31.7

31

32.6

Treatment, %

(n = 427)

(n = 280)

(n = 147)

Intensive care admission

32.6

36.4

25.2

Tocilizumab

65.1

69.3

57.2

Siltuximab

3

4.3

0.7

Corticosteroids

41.6

48.2

27.9

*Adapted from Le Gouill et al.1

Clinical outcomes

At a median follow-up of 6.5 months (range, 6.1−7.1), ORR was 60%, with 50.7% of patients in CR and 25% with PD. By 12 months, ORR was 68.7%, with 59.9% of patients in CR and 19.0% with PD.

Comparison of OS, PFS, and DOR at 6 months can be seen in Table 3. PFS in all patients with progressive disease at 6 months of treatment is reduced, with increased risk of early relapse.

Table 3. Clinical outcomes of patients with DLBCL in the DESCAR-T registry*

Outcome

CAR-T treated patients
% (range)

Untreated patients
% (range)

OS at 6 months

83.7 (79.7−86.9)

5.5 (1.1−15.6)

PFS at 6 months

(550 patients)

44.5 (39.6−49.2)

n/a

DOR at 6 months

(356 patients with response to treatment)

57.7 (51.6−63.3)

n/a

Outcome

Axi-cel treated patients

Tisa-cel treated patients

PFS at 6 months in patients in CR/PR/SD

61.4 (50−71)

52.5 (36.7−66

PFS at 6 months in patients with PD

38.2 (29.5−46.9)

17.1 (9.7−26.4)

OS at 6 months in patients in CR/PR/SD

87 (77−92.8)

88.2 (73.8−95)

PFS at 6 months in patients with PD

69.7 (60.5−77.1)

59.1 (47−69.3)

CR, complete remission; DOR, duration of response; n/a, not available; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial remission; SD, stable disease.
*Adapted from Le Gouill et al.1

Conclusion

The data from the DESCAR-T database/registry appears to support the work previously done in clinical trials, generating real-world evidence that CAR-T therapy is an effective routine treatment for patients with DLBCL. Data are similar between axi-cel and tisa-cel with no clear evidence of superiority. The registry did not find any evidence of novel toxicity patterns in patients receiving CAR-T cell therapy, adding to existing real-world evidence.

  1. Le Gouill S, Bachy E, Di Blasi R, et al. First results of DLBCL patients treated with CAR-T cells and enrolled in DESCAR-T registry, a French real-life database for CAR-T cells in hematologic malignancies. Oral presentation #S216. EHA2021; June 9, 2021; Virtual.

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