Global First: Chinese CAR-T Therapy Simultaneously Cures Tumor and Lupus Erythematosus
China make advanced medical treatment affordable
Wang Fang (pseudonym), residing in Yichang, Hubei, China, underwent a life-threatening ordeal. This patient in her forties had been suffering from systemic lupus erythematosus for over 20 years. What exacerbated her agony was the excruciating pain in her right leg since June 2019, which forced her into a wheelchair. Local hospital diagnosis revealed an aggressively invasive tumor—diffuse large B-cell lymphoma.
In mid-August 2019, Wang Fang followed a relative’s advice and sought treatment at Peking University Shenzhen Hospital (hereinafter referred to as “PKU Shenzhen Hospital”) in Shenzhen, where she was fortunate to participate in clinical trials for blood tumors. In mid-September 2019, she underwent the compound dual-target CAR-T (CD19/BCMA) cell immunotherapy.
Miraculous changes occurred a month after treatment; her lymphoma vanished entirely. Two months later, she was freed from the wheelchair and could walk independently. The nine-month follow-up, more astonishingly, revealed not only the complete disappearance of lymphoma but also the reversal of her long-standing stubborn lupus erythematosus antibodies, signifying her clinical cure from lupus.
This is the first documented instance globally where compound dual-target CAR-T cell immunotherapy cured diffuse large B-cell lymphoma and refractory lupus erythematosus—a significant breakthrough in Shenzhen’s oncology clinical research and treatment field.
This patient, originally from another region, had relied on steroids and other drugs to manage her condition for over 20 years due to systemic lupus erythematosus. However, the intensified pain in her right leg in June 2019 led to the diagnosis of an invasive tumor, rapidly deteriorating her condition and confining her to a wheelchair.
When faced with chemotherapy recommendations at the local hospital, Wang Fang declined due to the side effects she had previously experienced. Fortunately, a relative’s recommendation brought her to PKU Shenzhen Hospital. With the doctors’ dedicated assistance, Wang Fang participated in the clinical trial of CAR-T cell immunotherapy.
CAR-T cell therapy is an advanced treatment method that transforms a patient’s own T cells into CAR-T cells capable of identifying and attacking tumor cells. Since its successful treatment of the first case of acute lymphoblastic leukemia in the United States in 2012, this treatment has gradually become a groundbreaking technology in the field of tumor therapy. The Blood Department of PKU Shenzhen Hospital, as a pioneer, has completed over 30 cases of CAR-T cell therapy clinical trials, offering hope for those patients in critical conditions with ineffective traditional treatments.
Considering the uniqueness of Wang Fang’s disease, the team designed a compound dual-target CAR-T cell immunotherapy targeting both CD19 and BCMA. The success of this advanced therapy made Wang Fang the first case globally to be cured of lupus erythematosus using CAR-T cell therapy.
One month after treatment, she no longer needed wheelchair assistance; two months later, she could walk independently; and nine months later, besides the complete eradication of the tumor, the lupus erythematosus-related antibodies turned negative, leading to her clinical cure without relying on medication for her daily life.
Director Zhang Hongyu from the Blood Department of PKU Shenzhen Hospital stated that this successful case marks a significant breakthrough in CAR-T cell therapy, offering the possibility of cure to more patients. This successful clinical trial was also reported at the 61st American Society of Hematology (ASH) Annual Meeting, highlighting PKU Shenzhen Hospital’s significant contributions to the medical field.
After enduring this arduous battle, Wang Fang has regained her health and freedom. She expresses gratitude for the exceptional skills and selfless assistance of the medical team at PKU Shenzhen Hospital. Currently, for nine months, she has not taken any medication, regaining her beautiful hair and radiating vitality, looking forward to the future.
The appearance of this successful case brings hope and inspiration to the global medical community, showcasing the potential of CAR-T cell therapy in continuous exploration. The Blood Department team at PKU Shenzhen Hospital intends to continue exploring more effective and safer treatment approaches, bringing more hope for patients.
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.