-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3472 Safety and Efficacy of GPRC5D CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Translational Research, drug development, Diseases, Therapies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Shiqi Li, MD1*, Zhongtao Yuan, MD2*, Lin Liu2*, Yu Li, MD1*, Le Luo, MD2*, Yingnian Chen, MD1*, Lihua Zhang, MD1*, Guangchao Li, PhD3*, Min Luo, PhD4*, Kaikai Zeng, PhD5*, Donghui Ma, PhD5* and Sanbin Wang Sr., MD, PhD2*

1920th Hospital of Joint Logistics Support Force, Kunming, China
2Department of Hematology, 920th Hospital of Joint Logistics Support Force, Kunming, China
3Guangzhou Bio-gene Technology Co., Ltd, Guangzhou, China
4Guangzhou Bio-gene Technology Co., Ltd, GUANGZHOU, China
5DIMA Biotechnology, LTD, Wuhan, China

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have shown breakthrough therapeutic effects in treating relapsed/refractory (R/R) multiple myeloma patients. However, relapses, including some that are BCMA negative, remain a challenge.

Here we have developed a second-generation GPRC5D CAR-T, composed of a GPRC5D-binding scFv (derived from a humanized rabbit monoclonal antibody), a 4-1BB costimulatory domain, and a CD3ζ signaling domain. Following pre-clinical studies, we initiated a phase 1 dose-escalation clinical trial. Lymphodepletion with fludarabine and cyclophosphamide was performed before administering 3E6, 6E6, or 1E7/kg anti-GPRC5D CAR T cells.

To date, we have enrolled a total of 7 R/R MM patients, including 3 patients with prior BCMA CAR-T treatment. All patients received autologous CAR T-cell infusions and were clinically evaluated between February 7th, 2023, and June 26th, 2023. No dose-limiting toxicities (DLT) were observed, even at the highest dose of 1E7/kg. Grade 3 or higher adverse events (AEs) were mainly hematological toxicities, such as neutropenia (6 [85.7%]), anemia (3 [43%]), and thrombocytopenia (3 [43%]). Cytokine release syndrome occurred in 6 (85.7%) of 7 patients, with all cases classified as grade 1 or 2. Notably, no neuro-toxicities were observed in any of the seven patients.

The overall response rate was 85.7% (6/7 patients), comprising 3 complete responses or better, 3 partial responses, and one no-response (NR). The NR patient had previously shown no response to BCMA CAR-T therapy, with FACS analysis confirming the absence of both BCMA and GPRC5D on their tumor cells. Interestingly, the other two patients previously treated with BCMA CAR T-cell therapy, one reached complete response (CR), and the other reached partial response (PR). Remarkably, one patient diagnosed as COVID-19 positive two days before CAR-T infusion still received the CAR-T cell product, which led to a dramatic in vivo expansion of CAR-T cells, resulting in CR within one month after cell infusion.

In conclusion, GPRC5D CAR T-cell therapy demonstrated promising clinical efficacy and tolerable safety in patients with R/R MM. For those who relapsed after anti-BCMA CAR T-cell therapy, GPRC5D CAR T-cell therapy offered an effective option (NCT05739188)."

Disclosures: Li: Guangzhou Bio-gene Technology: Current Employment. Luo: Guangzhou Bio-gene Technology: Current Employment. Zeng: DIMA Biotechnology, LTD: Current Employment. Ma: DIMA Biotechnology, LTD: Current Employment.

*signifies non-member of ASH