Study of tandem CD19/CD20 CAR-engineered T cells

During the American Society of Clinical Oncology (ASCO) Virtual Meeting 2020, Yajing Zhang presented the results of an open-label, single-arm, phase I/IIa clinical trial (NCT03097770) evaluating the safety and efficacy of tandem CAR T cells targeting CD19 and CD20 in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL).¹

Study design

The study enrolled 99 patients aged 16–70 years who underwent previous therapy with anti-CD20 monoclonal antibody and anthracycline. Patients included in the study had R/R B-cell NHL, Eastern Cooperative Oncology Group (ECOG) performance status between 0–2, life expectancy ˃ 3 months, adequate organ function, and measurable or assessable disease according to the Cheson et al. (2007) criteria.^1,2

The primary objective of the study was the evaluation of safety and tolerability of the tandem CD19/CD20 CAR-engineered T cells. Secondary objectives were, overall response rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).¹

After leukapheresis and conditioning chemotherapy, 87 patients received a single infusion of tandem CD19/CD20 CAR-engineered T cells at a dose of 0.5×10⁶─10×10⁶ cells/kg of body weight on Day 0, and 74 patients were followed up ≥ 3 months before the cut-off date.¹

Patient characteristics¹

The baseline patient characteristics are reported in Table 1.

Table 1. Patient characteristics¹

ASCT, autologous stem cell transplant; CAR T-cell, chimeric antigen receptor T cell; DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; FL, follicular lymphoma; PMBCL, primary mediastinal B-cell lymphoma; tFL, transformed FL
Characteristic, n (%)	Infused patients (n = 87)
Age, years
< 60	71 (82)
≥ 60	16 (18)
ECOG performance status score
0─1	54 (62)
2	33 (38)
Disease stage at study entry
I/II	13 (15)
III/IV	74 (85)
Diagnosis on central histologic review
DLBCL	58 (66)
tFL	6 (7)
FL	13 (15)
PMBCL	5 (6)
Others	5 (6)
Previous lines of anti-neoplastic therapy
≤ 2	23 (27)
3─5	49 (56)
≥ 6	15 (17)
Refractory or relapse
Refractory	70 (80)
Relapse to second-line or later therapy	17 (20)
Refractory after ASCT	12 (14)
Relapse after previous CD19 CAR T-cell therapy	9 (10)
Double or triple hit
Yes	30 (34)
No	38 (44)
Missing data	19 (22)

Results¹

Safety

Sixty-two patients (71%) developed cytokine release syndrome (CRS), but the majority were of Grade 1 or 2 (61%). The median time from infusion to CRS onset was one day (range, 1─5) and the median CRS duration was six days (range, 1─9). Grade 3 CRS occurred in 10% of patients with a median time of onset of one day post infusion (range, 1─2).

Other commonly reported adverse events within one month of infusion that might have been related to the treatment were leukopenia, pyrexia and anorexia.

Efficacy

The efficacy analysis was performed on 74 patients. After a median follow-up of 13.5 months (interquartile range, 33.2─3.3), 62 patients (84%) had an objective response, and 55 (74%) achieved a CR. The median PFS and OS were not reached for all patients. The PFS rates at 6 and 12 months were 76% and 59%, respectively. DOR rates were 94% at 6 months and 74% at 12 months.

Conclusion

The preliminary results on the optimized tandem CD19/CD20 CAR-engineered T cells showed a tolerable safety profile with manageable CRS and a promising overall efficacy.