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

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*

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
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)

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*

*Adapted from Le Gouill et al.1
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

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*

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
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)

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.