Preventative Kineret May Ease CAR-T Cell Therapy Side Effects in Multiple Myeloma

In patients with relapsed or refractory multiple myeloma (RRMM) being treated with the CAR-T cell therapy orva-cel (orvacabtagene autoleucel), the incidence of moderate or worse cytokine release syndrome (CRS) was lower in patients receiving preventative Kineret (anakinra) .

CRS is a side effect that can occur in patients being treated with immune-based treatments, such as CAR-T cell therapy, and happens when there is a large release of inflammatory cytokines into the blood stream.

The findings also showed that the use of Kineret prophylaxis (given to prevent the side effect) had no adverse effect on the incidence of neurological events (NEs), infection, macrophage activation syndrome (a severe complication of rheumatic disease)/hemophagocytic lymphohistiocytosis (a severe systemic inflammatory syndrome that can be fatal), orva-cel expansion or disease response.

The data were presented at the European Hematology Association (EHA) 2021 Virtual Congress.

To conduct their study, researchers enrolled 33 patients with RRMM who had previously received at least three prior lines of therapy in the phase 1/2 EVOLVE study. Kineret 100 mg was administered via injection the night before orva-cel infusion, three hours before the infusion on day one and every 24 hours on days two through five. If patients developed CRS, the dosing was increased to every 12 hours.

The average follow-up was three months for the Kineret prophylaxis group of 14 patients and 8.8 months in the non-Kineret prophylaxis group of 19 patients. In the Kineret prophylaxis and non-Kineret prophylaxis groups, the median number of prior regimens was six and five, respectively; bridging therapy was used in 57% and 68% of patients, respectively.

The total frequency of CRS was similar in the two groups, however there were fewer moderate events in patients receiving Kineret prophylaxis. Actemra (tocilizumab) and corticosteroid use was lower in patients treated with Kineret prophylaxis.

“Most baseline demographics and disease characteristics were similar between groups,” said Dr. Luciano J. Costa, Associate Director for Clinical Research, O’Neal Comprehensive Cancer Center at University of Alabama at Birmingham School of Medicine, during a presentation of the findings.

After a two-month assessment, the objective response rate (ORR), which shows how well the treatment is working, was 100% in the Kineret prophylaxis group and 95% in the non-Kineret prophylaxis group.

“At month six after orva-cel treatment, 87.5% of Kineret prophylaxis patients and 62% of non-Kineret prophylaxis patients retained detectable CAR transgene copy,” Costa concluded.

The authors noted that these results warrant further exploration of Kineret prophylaxis in combination with CAR-T cell therapy in these patients.

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