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4 months ago Myeloma

🩸 Breakthrough in Multiple Myeloma Treatment! 🩺

🩸 Breakthrough in Multiple Myeloma Treatment! 🩺

LANCET

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!

#MultipleMyelomaResearch #CARTTherapy #GPRC5D #MedicalBreakthrough #cart #multiplemyeloma #chinesecart #cartcell #carttherapy #LANCET #Haematology #CARTCell

7 months ago CAR-T

Breakthrough medical research in China brings hope for multiple myeloma patients.

Eque-cel brings new treatment prospects for multiple myeloma.

    From December 9th to 12th, the Annual American Society of Hematology Meeting (ASH 2023) was held in San Diego, USA. At this conference, the FUMANBA-1 study, led by Professors Chunrui Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Lugui Qiu from the Institute of Hematology, Chinese Academy of Medical Sciences, conducted at 14 medical centers nationwide, demonstrated the efficacy and characteristics of sustained minimal residual disease (MRD) negativity in multiple myeloma (MM) patients treated with Eque-cel injection (CT103A). Their achievements were included in the oral presentation at the conference.

Current MM Treatment and Challenges of CAR-T Therapy CAR-T cell therapy holds significant importance in the treatment of multiple myeloma, overcoming patients’ immunodeficiency and tolerance issues. Currently, China has approved three CAR-T cell drugs targeting multiple myeloma. Compared to traditional treatments, CAR-T cell therapy enhances immune function without relying on the major histocompatibility complex (MHC), improving the activity of NK cells, T cells, and B cells while effectively activating T cells. However, despite significant advancements in CAR-T cell therapy in the MM field, some patients still struggle to maintain treatment effectiveness, leading to potential relapses, with antigen escape being one of the important mechanisms causing relapse.

Furthermore, the safety of CAR-T therapy is a major concern, including adverse reactions such as cytokine release syndrome (CRS), neurotoxicity, infections, B cell depletion, and hypogammaglobulinemia. Hence, monitoring patient indicators throughout the entire CAR-T treatment process, from pre-treatment to infusion, is crucial for timely intervention in adverse reactions.

    100% MRD Negativity Rate for CR and Above Patients! Eque-cel Injection Brings Redemption for Multiple Myeloma

    Eque-cel injection (CT103A) is a fully humanized CAR-T cell therapy drug targeting B cell maturation antigen (BCMA), approved by the National Medical Products Administration (NMPA) for adult refractory/relapsed multiple myeloma patients in China. In the Phase II FUMANBA-1 study, this treatment showed significant and sustained efficacy.

As of December 31, 2022, with a median follow-up time of 18.07 months, deep and sustained remissions were observed in 103 evaluable patients. The overall response rate (ORR) among these 103 patients was 96.1%, with a strict complete response (sCR)/complete response (CR) rate of 77.7%. Among 91 subjects with no previous CAR-T treatment history, the ORR was 98.9%, and the sCR/CR rate reached 82.4%, with a 12-month progression-free survival (PFS) rate of 85.5%.

The minimal residual disease (MRD) negativity rate for the entire population was 94.2%, reaching 100% for CR and above patients. The median time to MRD negativity was 15 days, and 80.8% of patients maintained MRD negativity 12 months post-infusion. Moreover, the Eque-cel injection exhibited a relatively long median persistence in the body, lasting up to 307.5 days.

According to Professor Chunrui Li, “The sustained MRD-negative status is closely related to the improvement in PFS of patients receiving Eque-cel treatment.”

Professor Chunrui Li’s team studied the characteristics of patients maintaining MRD negativity for ≥6 months and ≥12 months in the FUMANBA-1 study. The research revealed that among 88 patients achieving MRD negativity, 78.4% maintained MRD negativity for at least 6 months, and 74.4% sustained MRD negativity for at least 12 months. Patients with sustained MRD negativity showed longer…

Professor Chunrui Li:

Chief Physician, Doctoral Supervisor

Secretary of the Hematology Department Party Committee,  Deputy Director of Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Professional

Focus: Immunotherapy for Hematological Malignancies

Member of the 11th Committee of the Plasma Cell Disease Professional Group of the Hematology Branch of the Chinese Medical Association

Chairman of the Expert Committee on Hematology (Hubei), Geriatrics Branch, Chinese Geriatrics and Gerontology Society

Standing Committee Member of the Geriatric Medicine Branch, Chinese Geriatrics and Gerontology Society

Youth Committee Member of the Oncology Branch, Chinese Anti-Cancer Association Committee Member of the Myeloma and Plasma Cell Disease Professional Group, 5th Committee of the Chinese Society of Clinical Oncology (CSCO) Leukemia Alliance & Lymphoma Alliance

Vice Chairman of the Blood Branch of the Hubei Medical Immunology Association Principal Investigator of four National Natural Science Foundation projects; published more than 20 SCI papers as first author or corresponding author, including Blood.

 

#EqueCelTreatment #MMResearch #CARTTherapy #MRDNegativity #CancerTreatment #MedicalBreakthrough #FUMANBA1Study #Immunotherapy #CancerResearchUpdate #CancerResearch #ASH2023 #BloodCancer #EqueCel #MRD #MultipleMyeloma

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