Anti-CD19 CAR T-cell therapy for patients with primary or secondary CNS lymphoma

Patients with relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL) have a dismal prognosis; as such, there is a need for novel treatment strategies for these patients.¹ Several trials, including  ZUMA-1 (NCT02348216) and  JULIET (NCT02445248), have demonstrated the efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory large B-cell lymphoma¹; however, there is a lack of data on the safety and efficacy of anti-CD19 CAR T-cell therapy in patients with PCNSL/SCNSL.¹

During the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Ossami Saidy presented results from an analysis of CD19-targeted CAR T-cell therapy in patients with PCNSL or SCNSL from the EBMT and GoCART coalition.¹ We summarize this presentation below.

Study design¹

• This analysis included adult patients aged ≥18 years with PCNSL or SCNSL who received their first CAR T-cell therapy between January 2018 and February 2023.
• The primary endpoints were overall survival and progression-free survival.
• Secondary endpoints included relapse incidence, non-relapse morality, and toxicity.
• Data was obtained from the EBMT registry and a questionnaire.

Key findings¹

Patient characteristics

A total of 95 patients with a median age of 62.6 years were included in this analysis. (Table 1).

Table 1. Patient characteristics*

Auto-HSCT, autologous hematopoietic stem cell transplantation; CAR, chimeric antigen receptor; CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; PCNSL, primary central nervous system lymphoma; SCNSL, secondary CNSL. *Adapted from Ossami Saidy.1 †n = 93. ‡n = 69. §n = 93. ‖n = 89.
Patient characteristics, % (unless otherwise specified)	All patients (N = 95)
Median age, years (range)	62.6 (23–80)
Aged >70 years	25
Gender
Male, n	55
Female, n	40
Type of CNS lymphoma
PCNSL	10.5
SCNSL	89.5
ECOG Performance Status ≥2†	22.6
Number of prior lines of therapy‡
1	5.8
2	30.4
≥3	63.8
Previously auto-HSCT§	32.3
Remission status at CAR T-cell infusion‖
Stable disease/progressive disease	67.4
Partial remission	24.7
Complete remission	7.9

Survival outcomes

• After a median follow-up of 20.1 months, the 2-year progression-free survival and overall survival rates were 38.1% and 48.4%, respectively (Figure 1).
• Patients who received CAR T-cell therapy in complete or partial remission had improved survival outcomes compared with patients who had stable or progressive disease (Figure 1).

CR, complete remission; NRM, non-relapse mortality; OS, overall survival; PCNSL, primary central nervous system lymphoma; PD, progressive disease; PFS, progression-free survival; PR, partial remission; RI, relapse incidence; SCNSL, secondary central nervous system lymphoma; SD, stable disease.

*Data from Ossami Saidy¹

Toxicities

After a median follow-up of 27 months, the incidence rates of immune effector cell-associated neurotoxicity syndrome at 3 and 15 days were 17% and 43%, respectively.

Key learnings
Results suggest that anti-CD19 CAR T-cell therapy is effective in patients with PCNSL or SCNSL, with similar outcomes to patients with R/R large B-cell lymphoma without CNS involvement. Anti-CD19 CAR T-cell therapy should therefore be considered in all patients with R/R LBCL and CNS involvement.