**Bristol Myers Squibb and 2seventy bio Suspend KarMMa-9 Clinical Trial for Newly Diagnosed Multiple Myeloma Patients**
*October 2023*
Bristol Myers Squibb (BMS) and 2seventy bio, two prominent players in the biopharmaceutical industry, have recently announced the suspension of the KarMMa-9 clinical trial, a study aimed at evaluating the efficacy of a novel CAR-T cell therapy in newly diagnosed multiple myeloma patients. This decision has raised concerns within the medical community, as the trial was seen as a potential breakthrough in the treatment of this challenging blood cancer. The suspension underscores the complexities and risks inherent in developing cutting-edge therapies, particularly in the field of immuno-oncology.
### Background on Multiple Myeloma
Multiple myeloma is a type of blood cancer that originates in plasma cells, a type of white blood cell responsible for producing antibodies. It is the second most common hematologic malignancy, with an estimated 34,000 new cases diagnosed annually in the United States alone. Despite advances in treatment, multiple myeloma remains incurable, and patients often experience relapses after initial therapy. The disease is typically treated with a combination of chemotherapy, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. However, the prognosis for newly diagnosed patients, particularly those with high-risk disease, remains poor.
### The Promise of CAR-T Cell Therapy
Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a revolutionary approach in cancer treatment. CAR-T therapy involves genetically modifying a patient’s own T-cells to express a receptor that targets specific proteins on the surface of cancer cells. Once reintroduced into the patient’s body, these engineered T-cells can recognize and destroy cancer cells with high precision.
Bristol Myers Squibb and 2seventy bio have been at the forefront of CAR-T development, particularly in the treatment of multiple myeloma. Their flagship CAR-T product, *Abecma* (idecabtagene vicleucel), was approved by the U.S. Food and Drug Administration (FDA) in 2021 for the treatment of relapsed or refractory multiple myeloma in patients who have received at least four prior lines of therapy. Abecma targets the B-cell maturation antigen (BCMA), a protein commonly expressed on the surface of multiple myeloma cells.
The KarMMa-9 trial was designed to evaluate the use of Abecma in newly diagnosed multiple myeloma patients who were considered high-risk. The hope was that by using CAR-T therapy earlier in the treatment process, patients might achieve deeper and more durable responses, potentially improving long-term outcomes.
### The KarMMa-9 Trial: A Brief Overview
The KarMMa-9 trial was a Phase 3, randomized, open-label study that aimed to assess the safety and efficacy of Abecma in combination with standard-of-care therapies for newly diagnosed multiple myeloma patients. The trial enrolled patients who were considered high-risk based on specific genetic markers or disease characteristics, such as the presence of certain chromosomal abnormalities or high tumor burden.
The primary endpoint of the trial was progression-free survival (PFS), with secondary endpoints including overall survival (OS), overall response rate (ORR), and safety. The trial was seen as a critical step in expanding the use of CAR-T therapy beyond the relapsed/refractory setting and into earlier lines of treatment.
### Reasons for the Suspension
On October 2023, Bristol Myers Squibb and 2seventy bio announced the suspension of the KarMMa-9 trial. The companies cited safety concerns as the primary reason for the decision. While specific details regarding the nature of the safety issues have not been fully disclosed, it is known that CAR-T therapies can be associated with significant side effects, including cytokine release syndrome (CRS) and neurotoxicity. These side effects, while manageable in many cases, can be life-threatening if not properly controlled.
The suspension of the trial is a precautionary measure, allowing the companies to conduct a thorough review of the safety data and determine the best path forward. It is important to note that the suspension does not necessarily mean that the therapy is ineffective or that the trial will be permanently halted. However, it does highlight the challenges of developing CAR-T therapies, particularly in patient populations that may be more vulnerable to adverse events.
### Implications for Patients and the Field of Multiple Myeloma
The suspension of the KarMMa-9 trial is undoubtedly disappointing for patients and clinicians who were hopeful that CAR-T therapy could offer a new treatment option for newly diagnosed multiple myeloma. However, it is important to recognize that clinical trials are designed to rigorously evaluate both the safety and efficacy of new therapies, and suspensions are not uncommon in the development process.
For patients currently enrolled in the trial, Bristol