New gene therapy to treat adult patients with multiple myeloma

News 25/03/2022

EMA has recommended a conditional marketing authorisation in the European Union (EU) for Carvykti (ciltacabtagene autoleucel) for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies and whose cancer has worsened since they received their last treatment.

Multiple myeloma is a rare cancer of the plasma cells, a type of white blood cell that produces antibodies and is found in the bone marrow. In multiple myeloma, the proliferation of plasma cells is out of control, resulting in abnormal, immature plasma cells multiplying and filling up the bone marrow. When plasma cells become cancerous, they no longer protect the body from infections and produce abnormal proteins that can cause problems affecting the kidneys, bones or blood.

Despite the development and approval of a range of new medicines for the treatment of multiple myeloma over the past few years, there are limited therapeutic options for patients who have already received three major classes of drugs (immunomodulatory agents, proteasome inhibitors and monoclonal antibodies) and whose disease has come back or no longer responds to these medicines. Therefore, new medicines are needed for these patients.

Ciltacabtagene autoleucel, the active substance of Carvykti, is a chimeric antigen receptor (CAR)-T cell medicine. It is an advanced therapy for cancer that is based on collecting and modifying patient’s own immune T-cells to create a patient personalised treatment that is infused back.

Carvykti was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.

The main study on which the recommendation for a conditional marketing authorisation is based, is a single arm, open-label, multicentre clinical trial. The study investigated the efficacy and safety of ciltacabtagene-autoleucel in 113 adult patients with relapsed and refractory multiple myeloma who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and who didn’t respond to the last treatment regimen. About 84% of patients enrolled in the study responded to the treatment with a durable response (a period without disease signs or symptoms after treatment). Around 69% showed a complete response, meaning the signs of cancer disappeared.

The most common side effects are cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, infections and encephalopathy, i.e. a brain disorder. The consequences of CRS can be life-threatening and, in some cases, even fatal. Furthermore, other important safety aspects are neurologic toxicity, prolonged cytopenia and serious infections. Monitoring and mitigation strategies for these side effects are described in the product information and in the risk management plan that is an integral part of the authorisation.

Additional risk minimisation measures required from the marketing authorisation holder will ensure that centres that dispense the therapy are qualified to recognise and manage CRS and neurotoxicity associated with the treatment of Carvykti.

Additional efficacy and safety data are being collected through the submission of follow-up data from the main clinical trial and through an ongoing study that will compare the efficacy and safety of the medicine with standard triplet regimens in patients with relapsed and lenalidomide-refractory multiple myeloma.

Because Carvykti is an advanced-therapy medicinal product (ATMP), it was assessed by the Committee for Advanced Therapies (CAT), EMA's expert committee for cell- and gene-based medicines, and EMA’s human medicines committee (CHMP), which recommended approval based on the CAT assessment.

The opinion adopted by the CHMP is an intermediary step on Carvykti’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.


  1. The applicant for Carvykti is Janssen-Cilag International NV.
  2. Carvykti was designated as an orphan medicinal product on Cavrykti was accepted into the PRIME scheme
  3. Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designation should be maintained.

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