Redefining Hope for High-Risk RRMM Patients Worldwide: A Singaporean Patient`s Journey to China for Groundbreaking CAR-T Therapy

Redefining Hope for High-Risk RRMM Patients Worldwide: A Singaporean Patient`s Journey to China for Groundbreaking CAR-T Therapy

Multiple Myeloma

#MultipleMyeloma #CAR_Therapy #CancerTreatment #HRMM #MM #RRMM #CART

In the fight against multiple myeloma (MM), the last few decades have seen significant advancements, yet the disease remains notoriously difficult to cure, particularly in patients with relapsed/refractory multiple myeloma (RRMM). These patients face enormous challenges, as their options become increasingly limited after multiple lines of therapy have failed. However, hope has emerged in the form of BCMA CAR-T therapy, offering deep remission and long-term survival for those who had nearly lost hope.

One such case is a 58-year-old woman from Singapore, who after exhausting all available treatments in her home country, found new hope in China`s innovative CAR-T therapy. Diagnosed with MM in May 2021 following a month of severe back pain, she underwent a series of treatments including CD38 monoclonal antibodies, immunomodulatory drugs (IMiDs), proteasome inhibitors (PI), and XPO-1 inhibitors. Unfortunately, these therapies failed to halt the progression of her disease, which had become highly resistant to treatment.

In December 2023, she traveled to Beijing Chaoyang Hospital, Capital Medical University, where Professor Chen Wenming took charge of her case. The patient was diagnosed with high-risk MM (IgG-κ type) and admitted to the hospital on November 25, 2023, for CAR-T therapy.

#### The Treatment Journey: A Detailed Overview

Given the patient’s refractory nature and multiple prior treatments, Professor Chen devised a tailored treatment plan to improve her chances of survival and quality of life. In November 2023, her lymphocytes were collected to prepare the CAR-T cells. During this period, she received two cycles of D-PACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) chemotherapy in Singapore to control the extramedullary plasmacytoma.

In February 2024, she returned to Beijing for further evaluation, where her condition was assessed as showing minimal response (MR). She was then administered a lymphodepletion regimen of fludarabine and cyclophosphamide on February 29. The following month, she received a transfusion of BCMA CAR-T cells.

Within five days post-transfusion, the patient developed a fever, which peaked at 39°C. Fortunately, her oxygen saturation and heart rate remained normal, and she was diagnosed with Grade 1 cytokine release syndrome (CRS). After symptomatic treatment, her blood counts recovered by day 15, and she was discharged in stable condition.

Two weeks post-CAR-T therapy, her response was evaluated as a very good partial response (VGPR), and by the two-month mark, her condition had improved to complete remission (CR) with minimal residual disease (MRD) negativity.

#### Insights from Leading Experts

Professor Wee Joo Chng, a specialist in high-risk MM, noted the aggressive nature of the patient’s disease, marked by genetic abnormalities like 1q21+ and t(4;14). Despite the use of multiple potent therapies, including KRd, XVd, and Isa-Pd, the patient’s disease continued to progress rapidly. The emergence of the del(17p) mutation further complicated her prognosis, indicating the need for a novel therapeutic approach.

The FUMANBA-1 study has highlighted the effectiveness of China`s indigenous CAR-T product, Equecabtagene Autoleucel, in achieving deep remission and prolonging survival in RRMM patients. This case demonstrated the therapy`s potential to overcome poor prognostic factors and extend the patient’s survival. Notably, the patient experienced only mild CRS and no immune effector cell-associated neurotoxicity syndrome (ICANS) or infections during treatment. At the two-month follow-up, the patient’s condition had improved to CR with MRD negativity, suggesting that Equecabtagene Autoleucel could be a game-changer for high-risk RRMM patients.

#### A New Frontier in CAR-T Therapy

RRMM patients with double-hit characteristics often experience early relapse and progression, leading to shortened survival times. Traditional therapies, including IMiDs, PIs, and monoclonal antibodies, have failed to overcome these poor prognostic factors, indicating the urgent need for novel treatments. Real-world studies have shown that CAR-T therapy offers comparable progression-free survival (PFS) and overall survival (OS) rates in RRMM patients, regardless of high-risk cytogenetic abnormalities.

The FUMANBA-1 study revealed impressive outcomes for Equecabtagene Autoleucel in RRMM patients, with an overall response rate (ORR) of 98.9% and an MRD negativity rate of 97.8% among CAR-T-naive patients. The CR rate was 82.4%, and 81.7% of patients maintained MRD negativity for over a year.

Globally, four CAR-T products are currently available, and a recent study presented at the 2024 European Society for Blood and Marrow Transplantation (EBMT) compared the short- and long-term efficacy of these therapies. The study’s matching-adjusted indirect comparison (MAIC) analysis revealed that Equecabtagene Autoleucel had a 12-month PFS rate of 94.2%, higher than the 75% observed with Ciltacabtagene autoleucel (CARTITUDE-1 study). Furthermore, the 12-month sustained MRD negativity rate for Equecabtagene Autoleucel was 100%, compared to 53.1% for Ciltacabtagene autoleucel.

These findings suggest that Equecabtagene Autoleucel, a Chinese-developed BCMA CAR-T therapy, offers superior long-term efficacy compared to its U.S. counterpart. As the global community celebrates the first anniversary of its approval, Equecabtagene Autoleucel continues to bring hope to RRMM patients worldwide, further solidifying China’s leading role in the field of cellular therapy.

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8 months ago CAR-T

A Miraculous Journey: Israeli Artist Finds Cure for Multiple Myeloma in Hangzhou China

A Miraculous Journey: Israeli Artist Finds Cure for Multiple Myeloma in Hangzhou China

    In a remarkable medical story, we turn our attention to the experiences of a friend seeking treatment in Hangzhou China. Tali, a well-known artist from Israel. In 2012, she was diagnosed with multiple myeloma, a malignant blood disease, and after seeking treatment in various European countries, including Israel and France, she found no definitive cure. In a moment of despair, she discovered a solution from Hangzhou, China, through the European Bone Marrow Transplant Association.

    On October 6th, Tali and her family boarded a flight from Israel to Hangzhou. Under the meticulous care of Professor Huang He and his team at Zhejiang University’s First Hospital, Tali underwent over a month of intensive treatment. Today, Tali is finally on the road to recovery, expressing her gratitude to the medical staff through her preferred medium – art.

    In the hospital room, Tali and Professor Huang He share laughs and conversations. The weather looks promising, initially being skeptical about her health when arriving in Hangzhou, encouragement from the medical team reignited her hope for recovery. Using her artistic language, she documented every moment of the treatment process.

After undergoing treatment, the excruciating bone pain gradually lessened, indicating a positive turn in her health.

    “I can feel my body improving bit by bit. Green cells are gradually replacing the red ones, and my bone pain has completely disappeared. There are no tumor cells in the bone marrow anymore – they have vanished entirely.” Tali expressed.

    The advanced treatment utilized at Zhejiang University’s First Hospital involves cutting-edge blood cell separation technology. Lymphocytes are extracted and genetically engineered to attack malignant tumor cells, successfully curing multiple myeloma. This revolutionary technique is known as CAR-T cell therapy. Zhejiang University’s First Hospital stands out as one of the earliest and most experienced clinical research centers using this technology, making it a pioneer in the field.

    In here we bring you this inspiring story from Hangzhou, where art, science, and the human spirit come together in a tale of triumph over adversity.

#HangzhouMedicalMiracle #CARTCellTherapy #InspiringStories #MedicalAdvancements

9 months ago CAR-T

The latest research findings of BCMA CAR-T therapy for multiple myeloma in 2023 | Equecabtagene Autoleucel (FUCASO)

The latest research findings of BCMA CAR-T therapy for multiple myeloma in 2023 | Equecabtagene Autoleucel (FUCASO®)

    IASO Bio and Innovent presented their latest research findings on the Equecabtagene Autoleucel injection (brand name: FUCASO®) for multiple myeloma at the 2023 American Society of Hematology (ASH) Annual Meeting. This study was primarily based on a post-hoc analysis of the FUMANBA-1 study, an Ib/II phase research assessing the efficacy and safety of this therapy in treating patients with relapsed and refractory multiple myeloma (RRMM).

    As of December 31, 2022, with a median follow-up of 18.07 months, deep and sustained responses were observed in 103 evaluable patients. Among these patients, the overall response rate (ORR) was 96.1%, and the stringent complete response/complete response (sCR/CR) rate was 77.7%. Among subjects without prior CAR-T therapy, the ORR reached 98.9%, the sCR/CR rate reached 82.4%, and the 12-month progression-free survival (PFS) rate was 85.5%.

Minimal residual disease (MRD) negativity rate is 94.2% in the total evaluable patients, and all patients who achieved CR or above were MRD negative. The median time to achieve MRD negativity was 15 days, with 80.8% of patients remaining MRD negative at 12 months post infusion.

In addition, Equecabtagene Autoleucel could persist in the body for an extended period of time the median duration was 307.5 days. 12 months after infusion, 50% of patients had a vector copy number (VCN) above the lower limit of detection; and 24 months after infusion, VCN could still be detected in 40% of the patients.

The research findings indicate a strong correlation between sustained MRD negativity and patient progression-free survival (PFS), along with the continuous presence of Equecabtagene Autoleucel in the body, which correlates positively with sustained MRD negativity.

The Equecabtagene Autoleucel injection may improve the long-term survival prospects of RRMM patients, offering enduring deep remission and holding significant importance for the sustained maintenance of MRD negativity in patients.

About Multiple Myeloma (MM)

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there’s currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma. In the United States, MM accounts for nearly 2% of all cancer cases, and more than 2% of cancer-related deaths.

According to Frost & Sullivan, the number of new MM cases in the United States rose from 30,300 in 2016 to 32,300 in 2020 and is expected to increase to 37,800 by 2025. Additionally, the total number of patients diagnosed with MM increased from 132,200 in 2016 to 144,900 in 2020 and is expected to rise to 162,300 by 2025. In China, the number of new MM cases rose from 18,900 in 2016 to 21,100 in 2020 and is expected to increase to 24,500 by 2025. The total number of patients diagnosed with MM in China increased from 69,800 in 2016 to 113,800 in 2020 and is expected to rise to 182,200 by 2025.

About Equecabtagene Autoleucel

Equecabtagene Autoleucel is an innovative fully-human anti-BCMA CAR-T cell therapy that uses lentivirus as a gene vector to transfect autologous T cells. The CAR comprises a fully-human scFv, CD8a hinge and transmembrane, as well as 4-1BB-mediated co-stimulation and CD3ζ activation domains. Through rigorous screening and comprehensive in vivo and in vitro evaluation, Equecabtagene Autoleucel has been proven to possess potent and rapid anti-myeloma activity, along with outstanding safety, efficacy, and persistence results.

Equecabtagene Autoleucel has received acceptance for New Drug Application (NDA) from China’s National Medical Products Administration (NMPA) for the treatment of RRMM and has obtained IND approval from the U.S. FDA. Additionally, the company was granted Breakthrough Therapy Designation (BTD) by the NMPA in February 2021, Orphan Drug Designation (ODD) in February 2022, and Regenerative Medicine Advanced Therapy (RMAT) and Fast Track (FT) Designations from the FDA in February 2023. Besides multiple myeloma, NMPA has accepted its IND application for the new extended indication of Neuromyelitis Optica Spectrum Disorder (NMOSD). Innovent and IASO Bio are collaboratively developing Equecabtagene Autoleucel for the treatment of RRMM in mainland China.

About IASO Biotechnology

IASO Bio is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and autoimmune diseases. Leveraging its proprietary fully human antibody discovery platform (IMARS), high-throughput chimeric antigen receptor T-cell (CAR-T) drug screening platform, and proprietary manufacturing processes, IASO Bio is developing a robust clinical-stage pipeline of multiple autologous and allogeneic CAR-T and biologics product candidates. This pipeline comprises a diversified portfolio of over 10 novel products, including IASO’s flagship asset, Equecabtagene Autoleucel (CT103A), a fully human BCMA CAR-T injection.

In addition to Equecabtagene Autoleucel, the company’s pipeline includes the fully developed in-house human CD19/CD22 dual-targeted CAR-T cell therapy, which has received two IND clearances for treating relapsed/refractory B-cell non-Hodgkin’s lymphoma (r/r B-NHL) and relapsed/refractory acute B-lymphoblastic leukemia (r/r B-ALL). CD19/CD22 is currently in Phase I clinical trials for r/r B-NHL. It was also granted ODD by the FDA in October 2021. In the approximately 20 patients dosed to date in the investigator-initiated trial, there were no immune effector cell-associated neurotoxicity syndrome (ICANS) observed in any patient, and the rate of grade 3 cytokine release syndrome (CRS) was less than 5%, with the remainder of patients experiencing no CRS or less than grade 3.

Leveraging its strong management team, innovative product pipeline, integrated manufacturing, and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfill unmet medical needs to patients in China and around the world.

#BCMACART #EquecabtageneAutoleucel #FUCASO #ASH2023 #ClinicalResearch #Hematology #CARTtherapy #MRDnegative #CancerTreatment #MedicalInnovation #BloodCancer #OncologyResearch #DrugApproval #CellTherapy #CancerSurvival #FDAapproval #NMPAapproval #Biopharmaceutical #ClinicalTrials #MM

9 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