What are the products of CAR-T approved for multiple myeloma
What are the products of CAR-T approved for multiple myeloma
William Casler, a patient from France, was diagnosed with multiple myeloma in 2009, and his journey of fighting cancer has been long and winding. He underwent two transplant surgeries, participated in a clinical trial of the triplet therapy with Carfilzomib/Daratumumab/Dexamethasone, and later received Pomalidomide treatment. However, his blood counts (red blood cells, white blood cells, and platelets) struggled to reach normal levels.
Fortunately, he later received CAR-T cell therapy at the Saint-Louis Hospital in Paris, which alleviated some of his symptoms. His light chain levels decreased from nearly 900 to 6, and the measurable M-spike level was 4. With a series of subsequent treatments, William’s condition significantly improved.
I. What is Multiple Myeloma
Multiple myeloma (MM) is a malignant plasma cell neoplasm, accounting for approximately 10% of hematological malignancies. It is characterized by the clonal proliferation of malignant plasma cells in the bone marrow and the overproduction of a monoclonal immunoglobulin (M-protein), accompanied by end-organ damage.
Although the survival outcomes of multiple myeloma patients have improved significantly with the application of new therapeutic drugs such as monoclonal antibodies (e.g., Isatuximab, Daratumumab), proteasome inhibitors (Bortezomib, Carfilzomib), and immunomodulatory drugs (e.g., Thalidomide, Pomalidomide), almost all patients inevitably relapse due to drug resistance. Therefore, there is an urgent clinical need to explore novel treatment approaches.
Fortunately, with the development of precision medicine in recent years, researchers have identified specific therapeutic targets for multiple myeloma and developed emerging CAR-T cell therapies, which have been approved by the U.S. Food and Drug Administration (FDA), bringing new hope to patients with multiple myeloma.
II. CAR-T Cells with Built-in “GPS” for Precise Targeting of Multiple Myeloma
CAR-T cell therapy (Chimeric Antigen Receptor T-cell therapy) is a form of cellular immunotherapy that involves genetically modifying a patient’s T cells to express a specific chimeric antigen receptor (CAR), inducing an anti-tumor response.
The CAR mentioned here is a recombinant receptor for a specific antigen. Once infused back into the patient, it can rapidly generate tumor-specific T cells upon encountering the tumor, acting like a “navigation head” and mediating tumor killing through various mechanisms, including the release of cytotoxic granules containing perforin and granzymes, the production of pro-inflammatory cytokines, and the activation of the Fas/FasL pathway.
Currently, the B-cell maturation antigen (BCMA) is a widely used target for CAR-T cell therapy in multiple myeloma, bringing new hope to patients with relapsed or refractory disease.
III. Prominent CAR-T Products for the Treatment of Multiple Myeloma
1. Abecma – The World’s First Anti-BCMA CAR-T Therapy, with an Objective Response Rate of 72%
Abecma (Idecabtagene vicleucel) is the world’s first CAR-T therapy targeting BCMA, approved by the U.S. Food and Drug Administration (FDA) and the Japanese Ministry of Health, Labor, and Welfare for the treatment of relapsed or refractory multiple myeloma (R/R MM).
This approval was based on the pivotal Phase II “KarMMa” clinical trial, which enrolled 127 adult patients with relapsed or refractory multiple myeloma who had received at least three prior lines of anti-myeloma therapy (including immunomodulatory drugs, anti-CD38 monoclonal antibodies, and proteasome inhibitors).
After receiving Abecma treatment, the objective response rate (ORR) in the 100 evaluable patients was 72%, with a complete response rate of 28% and a median duration of response of 10.7 months.
2. Carvykti – The First FDA-Approved Domestic CAR-T Therapy, with an Objective Response Rate of 85%
Carvykti (Ciltacabtagene Autoleucel, cilta-cel) is the first FDA-approved domestic CAR-T therapy, independently developed by Legend Biotech. It was launched in the European Union and Japan in May and September 2022, respectively, and is primarily used to treat relapsed or refractory multiple myeloma (R/R MM).
This approval was based on the results of the CARTITUDE-1 study, which enrolled 97 adult patients with R/R MM who had received at least three prior lines of therapy. The results showed that almost all patients (98%) responded to the treatment, with 78% achieving complete remission in their bone marrow or blood, and a median duration of response of 22 months.
Currently, Carvykti-related trials have progressed to CARTITUDE-4, and Legend Biotech presented the latest research data at the 2023 ASCO meeting. The study enrolled 419 patients who had previously received one to three lines of therapy and were randomly assigned to the Ciltacabtagene Autoleucel group (cilta-cel, n=208) or the standard-of-care group (SOC, n=211).
After a median follow-up of 16 months, the risk of death or disease progression was reduced by 74% in the cilta-cel group, with an ORR of 85% and a complete response rate (CR) of 73%. In the SOC group, the ORR was 67%, and the CR was 22%. These results further validate the impressive performance of cilta-cel in the treatment of relapsed or refractory multiple myeloma.
3. Equecabtagene Autoleucel – China’s First Approved Cellular Therapy Product for Multiple Myeloma, with an Objective Response Rate of 96%
Equecabtagene Autoleucel is the world’s first fully human BCMA-targeted CAR-T product, independently developed and produced in China. It is also China’s first approved cellular therapy product for the treatment of multiple myeloma, leaving an indelible mark in China’s history of cancer treatment.
Developed jointly by IASO Bio and Innovent Biologics, Equecabtagene Autoleucel was approved by the National Medical Products Administration (NMPA) of China for the treatment of relapsed or refractory multiple myeloma (R/R MM) patients who had previously received at least three lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
This approval was based on data from the FUMANBA-1 multi-center Phase I/II clinical trial in China, which enrolled 103 patients with relapsed/refractory multiple myeloma. The updated results were presented at the 2023 ASCO annual meeting.
After a median follow-up of 13.8 months, in the 101 evaluable patients, the objective response rate (ORR) was 96%, with a stringent complete response/complete response rate (sCR/CR) of 74.3% (75/101), and 95% of the subjects achieved minimal residual disease (MRD) negativity.
Among the 12 patients who had previously received CAR-T therapy, 9 achieved a response, and 5 achieved a stringent complete response (sCR). In the 89 patients who had not previously received CAR-T therapy, the ORR was 98.9%, and the stringent complete response/complete response rate (sCR/CR) was 78.7%.
IV. Editor’s Remarks
Multiple myeloma accounts for approximately 10% of hematological malignancies, and its drug resistance and high relapse rate have been major factors affecting prognosis. In recent years, with the continuous development of novel drugs, targeted therapies, and immune cell therapies, especially the emergence of anti-BCMA CAR-T cell therapy, new hope has been brought to patients with relapsed or refractory multiple myeloma. 2021 marked the year of cellular immunotherapy in China, and currently, there are three CAR-T products approved globally for the treatment of multiple myeloma, two of which were developed in China, indicating China’s leading position in this field.
The editor also hopes that with the continuous advancement of CAR-T technology, more patients can benefit in the future, with longer survival and higher quality of life.