San Diego, California—Real-world evidence supports the use of axicabtagene ciloleucel (axi-cel) outside of the strict confinements of a clinical trial, although outcomes may be slightly inferior to those previously reported, according to retrospective study by Caron A. Jacobson, MD, Faber Cancer Institute, Boston, Massachusetts, and colleagues. Dr Jacobson shared findings from the study in a presentation at the 2018 ASH Annual Meeting.

Axi-Cel Use in the Real World

Existing data show that the best objective response rate (ORR) with long-term axi-cel use is 82% at 8.7 months, which was maintained over a follow-up period of 15.4 months. In addition, long-term follow-up revealed a complete response (CR) rate of 58%.

Building on these data, Dr Jacobson and colleagues evaluated the use of axi-cel outside of the clinical trial setting.

“We performed a multicenter retrospective study of axicabtagene ciloleucel given in a real-world setting where eligibility/management considerations may diverge from clinical trials. We evaluate efficacy and safety, and patient/disease factors associated with response and toxicity,” they explained.

The study included 104 patients with lymphoma; 94 (90%) of these patients had an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, 48 (46%) had a pre-lymphodepletion International Prognostic Index (IPI) score of ≥3, 28 (27%) had undergone autologous transplants, 3 (3%) had undergone allogenic stem cell transplants, 42 (40%) had bulky disease, and 42 (40%) received bridging therapy following leukapheresis.

By a follow-up of 6 months, 13 patients had their T-cells collected but had not received treatment with axi-cel because of progressive disease (n = 6), infection (n = 2), nonconforming cells (n = 3), complete response to bridging therapy (n = 1), or diagnosis of another malignancy (n = 1).

Patient Responses and Adverse Events

Among the 95 patients deemed evaluable, the best ORR was observed in 71% of patients, 44% had CR and 26% had partial response (PR). Among 51 patients with 6-months of follow-up, the ORR was 43%. Of the patients who had an initial PR, 50% went on to have a CR.

In univariate analysis, ECOG performance status, tumor bulk, IPI score, baseline C-reactive protein, and previous therapy with ibrutinib were significantly associated with a lack of response.

Approximately 95% of the treated patients had cytokine release syndrome (CRS); 17 (16%) had CRS grade ≥3 and 2 patients died. The median time to onset of CRS was 1 day, with a median duration of 6 days.

Neurologic toxicity was observed in 58 (76%) patients, 29 (38%) of whom had toxicity grade ≥3, with a median time to onset of 5 days and median duration of 8 days. One patient died because of neurologic toxicity. Tocilizumab and steroids were given to 67% and 78% of patients, respectively, to counter toxicity; 30% of patients required intensive care at a hospital or other healthcare facility.

A total of 11 axi-cel recipients have died—6 from progressive disease and 5 from toxicity.

Real-World Evidence vs ZUMA-1

Cytogenetic and immunohistochemistry staining revealed PD-L1–positive tumors refractory to CAR-T therapy in 3 patients. Peak CAR T-cell levels were seen at day 7 in all patients with increased expression of PD1, 41BB, Ki67, and CC3, indicating a positive response associated with these immune subsets. Subsequently, CAR T-cells reduced by day 14.

Dr Jacobson and colleagues noted that the deviation from the ORR and CR observed in the ZUMA-1 trial may be due to the inclusion of patients with a poorer performance status and/or different histologies.

“Rates of CRS and NT were similar to ZUMA-1, but toxicity was not associated with tumor bulk or response. It was associated with higher peak inflammatory markers and ALC [absolute lymphocyte count], which may reflect peak CAR T-cell levels, as shown previously. This suggests that unique combination approaches are necessary for specific patients/tumors,” they explained.

“These results support the use of axi-cel outside of strict clinical trial criteria, although the outcomes may be slightly inferior,” Dr Jacobson and colleagues concluded.—Janelle Bradley

Jacobson CA, Hunter B, Armand P, et al. Axicabtagene Ciloleucel in the Real World: Outcomes and Predictors of Response, Resistance and Toxicity. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 92.