A New Living Drug, CAR T-Cell Therapy, Receives FDA Approval for Multiple Myeloma

For patients who have already received four or more lines of therapy and have treatment-resistant or relapsed multiple myeloma, a new treatment option was approved by the FDA (United States Food and Drug Administration) on 28 February 2022.

The approved product is CAR T-cell therapy, a living drug in the immunotherapy class. Its active ingredient is ciltacabtagene autoleucel (cilta-cel), which will be marketed in the United States by Janssen and Legend Biotech under the name Carvykti.

Multiple myeloma is a type of hematological cancer that affects plasma cells originating from the B cells of our immune system. Multiple myeloma is cancer of the plasma cells. Plasma cells that become cancerous form a tumor called a plasmacytoma. These tumors are usually found in bone and rarely in other tissues. If a person has a single plasma-cell tumor, the disease is called isolated plasmacytoma. If there is more than one tumor, it is called multiple myeloma. The first symptom is bone pain in the back, hips and skull.

Living Drugs in Multiple Myeloma Treatment

A new target for multiple myeloma treatment is chimeric antigen receptor (CAR) T-cell therapy directed against B-cell maturation antigen (BCMA).

Two other treatments targeting BCMA are already on the United States market: idecabtagene vicleucel (Abecma), another CAR T cell approved by the FDA in March 2021, and a drug conjugate approved in August 2020, belantamab mafodotin (Blenrep).

Cilta-cel’s approval is based on clinical data first presented in December 2020 at the annual meeting of the American Society of Hematology, from the CARTITUDE-1 trial.

This clinical trial included 97 patients with relapsed/refractory multiple myeloma who had previously received a median of 6 lines of therapy (range, 3 to 18), including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

For most patients living with multiple myeloma, the treatment journey is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of treatment.

The results of the CARTITUDE-1 trial are therefore truly exciting, showing that Cilta-cel can provide deep and lasting responses and prolonged treatment-free intervals even in this heavily pretreated group of multiple myeloma patients.

Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, and then transferring them back into the patient.

Results from CARTITUDE-1 indicate that this one-time treatment produced deep and lasting responses.

Results

• The overall response rate was 98%, and most patients (78%) achieved a clear complete response, in which doctors could not observe any signs or symptoms of disease through imaging or other tests after treatment.
• At a median follow-up of 18 months, the median response duration was 21.8 months.

Cilta-cel’s approval offers physicians an immunotherapy treatment option that gives patients an opportunity to be free from antimyeloma therapies for a period of time.

As with other CAR T-cell therapies, there were serious side effects, and these living cancer drugs are available only through restricted programs under a risk evaluation and mitigation strategy.

The prescribing information for Cartykti contains a boxed warning mentioning cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.

The most common adverse reactions (reported in ≥20% of patients) were fever, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections with unspecified pathogens, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, shortness of breath, edema, viral infections, coagulopathy, constipation and vomiting.