CD19/20-Directed CAR-T Produces High Durable CR Rate in R/R Non-Hodgkin Lymphoma
Among 11 treated patients, 8 achieved a complete response.
CART19/20, an investigational autologous anti-CD19/anti-CD20 chimeric antigen receptor T-cell (CAR-T) therapy being evaluated in a phase 1 clinical trial (NCT04007029) for the treatment of relapsed/refractory (r/r) non-Hodgkin lymphoma, has produced a high durable complete response (CR) rate, according to data presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, 2023, in Orlando, Florida.
Among 11 patients who were treated with CART19/20 and were evaluable, 8 patients (73%) achieved a CR. Furthermore, 2 of these patients have maintained their CRs for 3 years. The overall response rate (ORR) was 91%. Benjamin R. Puliafito, a hematology/oncology fellow and clinical investigator at the University of California, Los Angeles, who presented the data, pointed out that 1 patient who achieved a CR but relapsed at 18 months post-treatment achieved a second CR after re-infusion with CART19/20. Puliafito additionally noted that at a median follow-up of 20.7 months, the median progression free survival was 18.2 months (2.6 - NE). The median overall survival has not yet been reached (5.7 months – NE).
In terms of safety, 6 of 10 evaluable patients experienced grade 1 cases of cytokine release syndrome (CRS), which was the highest grade of CRS reported. The onset of CRS in these patients ranged from 5 to 11 days after infusion (median, 8) and the duration of CRS ranged from 0 to 3 days (median, 2.5). None of the patients required corticosteroids, but 1 patient received tocilizumab for CRS. No cases of neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in the treated patients. Puliafito noted that 1 patient met the criteria for a dose-limiting toxicity as a result of prolonged thrombocytopenia which lasted past 120 days post-infusion. The patient died from a grade 5 case of hypocellular bone marrow. Two additional patient deaths occurred: 1 patient, whose disease was refractory to CART19/20, died from disease progression, and another patient died as a result of COVID-19 infection after experiencing disease progression.
“This lack of toxicity did come somewhat as a surprise,” Puliafito said in response to an audience question regarding the CRS and ICANS rates following the presentation. “I think 1 aspect of it is that we didn't need that high of a cell dose for this product to have efficacy. At 50 million cells is really where we have our dose expansion so that might be contributing to the low amount of toxicity. The other aspect that we think might be contributing is when the CAR T-cells start to really expand, which is at 14 days—later than the commercial products seem to expand, which is closer to 7 to 11 days—we see some anti-tumor effects before we see the peak expansion and that might delay or prevent neurotoxicity and CRS.”
While 12 patients were enrolled in the trial and underwent leukapheresis, 1 of these patients was not able to receive CART19/20 as a result of a manufacturing failure. The 11 patients treated with CART19/20, who had a median age of 58 years, included 5 patients with diffuse large B-cell lymphoma, 1 patient with primary mediastinal large B-cell lymphoma, 4 patients with follicular lymphoma (FL), and 1 patient with mantle cell lymphoma. The patients had received a median of 3 lines of prior therapy; 1 patient was previously treated with a CD19 T-cell engager. Puliafito stated that all patients with FL had experienced progressive disease within 24 months of the initial infusion. Eight of the 11 patients treated with CART19/20 received a dose of 50x106 CAR-T cells and 3 of the patients received a dose of 200x106 CAR-T cells. The trial’s design allowed for bridging therapy, and 9 of 11 patients received it.
“In conclusion, our bispecific CART19/20 cells have shown robust activity and overall safety in patients with r/r non-Hodgkin lymphoma...” Puliafito stated at the end of his presentation. “Overall, CART19/20 had a high ORR with a high CR rate and durable remissions.”
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