The ZUMA-1 trial studied the use of the Axicabtagene ciloleucel (Axi-cel, Yescarta®) as a CD19 targeted chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory aggressive B-cell lymphomas. It reported impressive results: an overall response rate (ORR) of 82 percent and complete response (CR) rate of 58 percent.
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Now investigators have longer follow-up data from high-risk patients involved in the ZUMA-1 trial as well as from real-world patients — many of whom would not have met the criteria to join the clinical trial — who received the drug after the FDA approved it in October 2017.
“With the relatively small number of patients who have been treated with CAR T-cell therapy, it’s important to follow their long-term outcomes,” says Brian T. Hill, MD, PhD, Director of the Lymphoid Malignancies Program at Cleveland Clinic Cancer Center.
“These studies report on those outcomes, give more detail on the response rates and the outcomes of patients with high-risk features to their lymphoma and also document the real-world clinical experience of patients taking the drug after FDA approval.”
Dr. Hill, who was an investigator with ZUMA-1, is a member of the consortium of investigators that presented data from both of these follow-up studies at the 2018 American Society of Hematology meeting.
High-risk patients equivalent response rate
For the study examining ZUMA-1 patients with high-risk B-cell lymphomas — also known as double-expresser B-cell lymphoma — the investigators found the CR rate was 53 percent (29/55) in patients with disease refractory to ≥ two consecutive prior lines of therapy and 72 percent (18/25) in patients who had relapsed within 12 months after autologous stem-cell transplantation.
They also assessed the genetics of the high-risk patients using 47 evaluable pretreatment tumor samples: 37 patients (79 percent) had high grade B-cell lymphoma or double-expressor B-cell lymphoma and had an ORR of 89 percent (33/37) including a CR rate of 68 percent (25/37). Forty-two percent of patients overall had ongoing responses with a median follow-up of 15.4 months including 49 percent (18/37) of patients with high-risk genetics.
“These data suggest that high-risk patients with large B-cell lymphomas seem to have equivalent response rates as other patients who are treated with CAR T-cell therapy,” says Dr. Hill. “In addition, if these high-risk patients achieve a complete remission, they’re likely to have durable remissions with the follow-up that’s available.”
Detectable B cells
To investigate the relationship between B-cell recovery and ongoing response, the researchers assessed B-cell levels over time. Overall, of the 87 evaluable patients, 47 percent had no detectable B cells at baseline, and the remainder had levels close to or below the lower level of quantification of the assay. In patients with ongoing responses at 12 months post treatment, 19 of the 35 (54 percent) patients with evaluable samples had detectable B cells at 12 months.
“These data suggest that persistence of CAR T-cells is not required in order for a patient to maintain their remission,” says Dr. Hill. “In other words, the CAR T-cells can get in, do their job then get out, and the patient will still remain in remission as opposed to the CAR T-cells having to stay in forever to eliminate any new cancer cells that many develop.”
Real-world patients also respond
The second study, a multicenter investigation that involved 163 patients, examined how well CAR T-cell therapy worked in regular patients after FDA approval in 2017.
“What was noteworthy about this study is these patients had more comorbidities, poorer performance status and other issues than the patients enrolled in ZUMA-1,” says Dr. Hill. “In fact, about half would not have been eligible for that clinical trial.”
Despite the difference in patient populations, he says, the real-world patients responded similarly to the drug as those in the trial with an ORR of 79 percent and CR of 50 percent.
What’s more, he says, the drug’s toxicities such as cytokine release syndrome (CRS) and neurologic events (NE) were not disproportionately higher for these patients as compared with the ZUMA-1 patients.
“I think these are potentially practice-informing preliminary data,” he says, “in justifying the use of Axi-cel to patients who are less fit than those originally studied.”