BCMA-directed CAR-T HBI0101 Demonstrates Safety and Efficacy in Patients With Light Chain Amyloidosis


All 8 patients with light chain amyloidosis who received HBI0101 responded.

HBI0101 (NXC-201), an autologous chimeric antigen receptor (CAR) T-cell therapy which targets B-cell maturation antigen (BCMA), has demonstrated safety and efficacy in patients with light chain amyloidosis (AL). The data was presented in a late-breaking session at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.

The data came from a phase 1a/1b dose escalation and safety clinical trial (NCT04720313) evaluating the treatment in patients with AL and multiple myeloma (MM). Nathalie Asherie, PhD, of the Department of Bone Marrow Transplantation and Cancer Immunotherapy at Hadassah Medical Center, who presented that data, indicated that the trial is notable for its inclusion of patients with AL.

“AL affects 5 in 1 million people, which is 10 times less common than MM,” Asherie said. “Due to the rarity and extreme frailty of this patient population, AL patients are invariably excluded from clinical trials and thus the treatment of AL is mostly extrapolated from those of MM. This includes chemotherapy, proteasome inhibitors, immunomodulatory agents, etc. However, due to their frail condition, AL patient may suffer from high toxicity from these treatments."

Among the 8 patients with AL included in the efficacy analysis, 5 achieved a complete hematologic response, 2 achieved a very good partial hematologic response, and 1 achieved a partial hematologic response. Organ responses were observed in 6 patients, with 1 patient achieving a complete organ response. Furthermore, 5 patients were reported to be minimal residual disease (MRD) negative at 30 days posttreatment.

“The efficacy results are very encouraging. All 8 AL patients responded to HBI0101...” Asherie said. “These fast and deep hematologic responses translated into organ responses in the majority of the patients... Four patients achieved fast, deep, and prolonged [hematologic] responses lasting over 8 months. [One patient] is still in remission 15 months following CAR T-cell infusion.”

In terms of safety, 6 of the 8 patients experienced cytokine release syndrome (CRS). Excepting 2 cases of grade 3 CRS, all CRS cases were grade 1-2. Both patients with grade 3 CRS cases required high flow oxygen use and 1 required vasopresser use. There were no cases of immune effector cell-associated neurotoxicity syndrome reported in the 8 patients. Asherie also noted that 2 patients experienced organ deterioration. She characterized the overall safety profile of HBI0101 as “clinically manageable”.

Asherie noted that the 8 patients entered the trial in poor condition; 7 of the patients had cardiac involvement and 3 had concomitant MM. The number of prior lines of therapy received by the patients ranged from 3 to 10 (median, 6). All of the patients had disease that was triple-drug refractory and 6 had disease that was penta-drug refractory. Asherie pointed out that some of the patients received BCMA targeted therapy prior to receiving the CAR-T.

“To conclude, at Hadassah Medical Center, we have treated a cohort of 8 AL patients using our own self-developed antiBCMA CAR T-cells,” Asherie said. “To the best of our knowledge, this is the largest AL cohort receiving such therapy. Our results suggest that the treatment is safe and may induce fast, deep, and sustained responses in some patients, although larger cohorts and longer follow-up are required to confirm this finding. While AL remains incurable, antiBCMA CAR T-cells represent a promising and potentially transformative approach to treating this disease. The recent licensing of our therapy by Immix Biopharma should help to extend the accessibility of antiBCMA CAR T-cells worldwide.”

Asherie N. BCMA-targeted CART (HBI0101), a safe and efficacious novel modality of treatment for LC amyloidosis patients. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Oral abstract session.
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