🩸 Breakthrough in Multiple Myeloma Treatment! 🩺

🩸 Breakthrough in Multiple Myeloma Treatment! 🩺

LANCET

🔬Targeting GPRC5D with CAR-T Cells shows immense potential in treating relapsed or refractory multiple myeloma patients.
Multiple myeloma, a malignant disease characterized by clonal plasma cell proliferation in the bone marrow, has remained incurable despite substantial progress in treatment methods such as systemic chemotherapy, radiation therapy, and hematopoietic stem cell transplantation (HSCT). However, CAR-T cell therapy targeting B-cell maturation antigen (BCMA) has demonstrated activity in treating relapsed or refractory multiple myeloma. Nonetheless, the escape of BCMA-low or BCMA-negative myeloma cells has led to treatment resistance and relapse, highlighting the need to explore new targets.

💪In February 2023, a groundbreaking study titled “GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-center, single-arm, phase 1 trial” was published in The Lancet Haematology. The study aimed to evaluate the activity and safety of G-protein-coupled receptor class 5 member D (GPRC5D) CAR-T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma.

🌈Promising Treatment Response with OriCAR-017 Infusion
All ten patients (100%) demonstrated an overall response, with 6 patients (60%) achieving a complete response and 4 patients (40%) showing very good partial responses. The patients with complete responses met stringent complete response criteria, and all patients achieved minimal residual disease (MRD) negativity by day 28. Serum M-protein concentrations gradually decreased, and patients’ clinical responses improved over time. The median time to the best response was 3.1 months, while the median time to a complete response or better was 4.1 months.

☀️Among the 5 patients who relapsed after BCMA CAR-T cell therapy, 2 patients achieved a stringent complete response, and 3 patients showed very good partial responses. Four patients had extramedullary disease at enrollment, with the largest tumor volume measuring 70 cm³. PET-CT scans revealed complete resolution of extramedullary lesions in three patients, while the extramedullary disease in one patient continued to shrink. Furthermore, no severe adverse events or treatment-related deaths were reported.

🌱Favorable Survival Outcomes after OriCAR-017 Infusion
⏰The median follow-up time for all patients was 238 days, with two patients progressing after achieving stringent complete remission. One patient experienced GPRC5D-positive relapse, with GPRC5D expression in malignant plasma cells increasing from 34.5% at baseline to 35.8% at relapse. The other patient experienced GPRC5D-negative relapse, with GPRC5D expression in malignant plasma cells decreasing from 86.8% at baseline to 6.9% at relapse. The remaining eight patients in ongoing remission were all negative for minimal residual disease, and no deaths occurred. The median progression-free survival time was not reached, but the estimated progression-free survival rate for all patients at nine months was 87.5%.

🧬Durable CAR-T Cell Persistence
✨CAR-T cell expansion was detected in all patients after infusion, with a median time to maximum CAR-T cell expansion (Cmax) of 10.0 days and a median Cmax of 7930 copies/μl. CAR-T cells exhibited favorable persistence in the body, with CAR-T cells still detectable in 90% of patients at one month, seven patients at three months, and four patients at six months.

🌟 The study results demonstrate that targeting GPRC5D with CAR-T cells in treating relapsed or refractory multiple myeloma patients is safe and shows promising activity. The observed targeted and off-target toxicities associated with GPRC5D were manageable, indicating the potential of GPRC5D as an effective immunotherapeutic target for multiple myeloma. These findings provide a foundation for subsequent phase 2 studies to further validate the efficacy and safety of targeting GPRC5D CAR-T cells in multiple myeloma.🦾

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🔬 Stay tuned for more updates on this groundbreaking research! Together, we can conquer multiple myeloma!

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