Contributions
Abstract: EP791
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
ZUMA-5 is a Phase 2 study of axi-cel anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL; follicular lymphoma [FL]; marginal zone lymphoma [MZL]). In the primary analysis, 11 patients (9 FL; 2 MZL) were retreated with axi-cel, achieving an overall response rate (ORR) of 100% (91% complete response [CR] rate) at a median follow-up of 2.3 months post-retreatment, with no Grade ≥3 cytokine release syndrome (CRS) or neurologic events (Chavez et al. ASH 2020. #2036).
Aims
To report updated clinical and translational outcomes with longer follow-up of axi-cel retreatment in patients with R/R iNHL in ZUMA-5.
Methods
Eligible adults with FL or MZL had R/R disease after ≥2 lines of therapy. Patients were considered for retreatment if they progressed after a response at month 3, had no evidence of CD19-negative relapse in biopsy, had no axi-cel–neutralizing antibodies, and had no Grade 4 CRS or neurologic events with first treatment. Retreatment was per investigator discretion. At both treatments, patients received axi-cel (2×106 CAR T cells/kg) after conditioning chemotherapy.
Results
As of 9/14/2020, 13 patients with iNHL (11 FL; 2 MZL) received axi-cel retreatment, with 2 patients retreated after the primary analysis. Before their first treatment, patients had median 4 prior lines of therapy; 85% had stage 3–4 disease; 82% had FLIPI of ≥3; 46% were POD24, and 77% had refractory disease.
Among the 13 retreated patients, 85% had a CR to first treatment. Median first duration of response (DOR) was 8.2 months. Detectable CD19 was confirmed in all evaluable biopsies from retreated patients at relapse, and median time from first treatment to retreatment was 10.6 months. Following retreatment, the ORR was 100% (77% CR rate). After a median follow-up of 11.4 months, the median DOR had not yet been reached; 46% of retreated patients had ongoing responses at data cutoff.
At first treatment, CRS occurred in 9 patients (5 Grade 1, 4 Grade 2); neurologic events occurred in 5 (3 Grade 1, 1 Grade 2, 1 Grade 3). At retreatment, CRS occurred in 8 patients (6 Grade 1, 2 Grade 2); neurologic events occurred in 4 (3 Grade 1, 1 Grade 2). Median peak levels of biomarkers typically associated with severe CRS and neurologic events were similar at retreatment and first treatment (IL-6, 7.7 vs 5.7 pg/mL; IL-2, 1.8 vs 0.9 pg/mL; IFN-γ, 62.9 vs 64.2 pg/mL).
In the 11 retreated patients with FL, tumor burden (median sum of product diameters [SPD]) was lower before retreatment vs first treatment (1416 vs 4770 mm2). Engraftment index (CAR T-cell expansion relative to sum of product diameters) is an indirect proxy for effector:target ratio and a key covariate of response to axi-cel (Locke et al. Blood Adv. 2020). Although median peak CAR T-cell levels appeared lower at retreatment vs first treatment (5.2 vs 14.3 CAR+ cells/µL blood), engraftment index was similar (0.003 vs 0.005 cells/µL×mm2).
Conclusion
Axi-cel retreatment achieved deep and durable responses, with an acceptable safety profile. Tumor CD19 positivity was maintained at relapse, and engraftment index was similar at both treatments, comparing favorably to previous reports in aggressive lymphomas (Locke et al. ASCO 2020. #8012). These data suggest axi-cel retreatment is a promising option for patients with R/R iNHL.
Keyword(s): CAR-T, Follicular lymphoma, Marginal zone, Retreatment
Abstract: EP791
Type: E-Poster Presentation
Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical
Background
ZUMA-5 is a Phase 2 study of axi-cel anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL; follicular lymphoma [FL]; marginal zone lymphoma [MZL]). In the primary analysis, 11 patients (9 FL; 2 MZL) were retreated with axi-cel, achieving an overall response rate (ORR) of 100% (91% complete response [CR] rate) at a median follow-up of 2.3 months post-retreatment, with no Grade ≥3 cytokine release syndrome (CRS) or neurologic events (Chavez et al. ASH 2020. #2036).
Aims
To report updated clinical and translational outcomes with longer follow-up of axi-cel retreatment in patients with R/R iNHL in ZUMA-5.
Methods
Eligible adults with FL or MZL had R/R disease after ≥2 lines of therapy. Patients were considered for retreatment if they progressed after a response at month 3, had no evidence of CD19-negative relapse in biopsy, had no axi-cel–neutralizing antibodies, and had no Grade 4 CRS or neurologic events with first treatment. Retreatment was per investigator discretion. At both treatments, patients received axi-cel (2×106 CAR T cells/kg) after conditioning chemotherapy.
Results
As of 9/14/2020, 13 patients with iNHL (11 FL; 2 MZL) received axi-cel retreatment, with 2 patients retreated after the primary analysis. Before their first treatment, patients had median 4 prior lines of therapy; 85% had stage 3–4 disease; 82% had FLIPI of ≥3; 46% were POD24, and 77% had refractory disease.
Among the 13 retreated patients, 85% had a CR to first treatment. Median first duration of response (DOR) was 8.2 months. Detectable CD19 was confirmed in all evaluable biopsies from retreated patients at relapse, and median time from first treatment to retreatment was 10.6 months. Following retreatment, the ORR was 100% (77% CR rate). After a median follow-up of 11.4 months, the median DOR had not yet been reached; 46% of retreated patients had ongoing responses at data cutoff.
At first treatment, CRS occurred in 9 patients (5 Grade 1, 4 Grade 2); neurologic events occurred in 5 (3 Grade 1, 1 Grade 2, 1 Grade 3). At retreatment, CRS occurred in 8 patients (6 Grade 1, 2 Grade 2); neurologic events occurred in 4 (3 Grade 1, 1 Grade 2). Median peak levels of biomarkers typically associated with severe CRS and neurologic events were similar at retreatment and first treatment (IL-6, 7.7 vs 5.7 pg/mL; IL-2, 1.8 vs 0.9 pg/mL; IFN-γ, 62.9 vs 64.2 pg/mL).
In the 11 retreated patients with FL, tumor burden (median sum of product diameters [SPD]) was lower before retreatment vs first treatment (1416 vs 4770 mm2). Engraftment index (CAR T-cell expansion relative to sum of product diameters) is an indirect proxy for effector:target ratio and a key covariate of response to axi-cel (Locke et al. Blood Adv. 2020). Although median peak CAR T-cell levels appeared lower at retreatment vs first treatment (5.2 vs 14.3 CAR+ cells/µL blood), engraftment index was similar (0.003 vs 0.005 cells/µL×mm2).
Conclusion
Axi-cel retreatment achieved deep and durable responses, with an acceptable safety profile. Tumor CD19 positivity was maintained at relapse, and engraftment index was similar at both treatments, comparing favorably to previous reports in aggressive lymphomas (Locke et al. ASCO 2020. #8012). These data suggest axi-cel retreatment is a promising option for patients with R/R iNHL.
Keyword(s): CAR-T, Follicular lymphoma, Marginal zone, Retreatment