Ciltacabtagene autoleucel (Cilta-cel) therapy



Sept 2022: Because it is created from your own white blood cells that have been altered (genetically modified) to recognise and destroy your multiple myeloma cells, Cilta-Cel CAR T-Cell therapy (ciltacabtagene autoleucel) differs from other frequently used cancer medicines (such as chemotherapy). 

According to a press release from Legend Biotech Corporation, the FDA has approved ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of adults with relapsed or refractory multiple myeloma who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The FDA extended the review period for cilta-cel, a chimeric antigen receptor (CAR) T-cell therapy with two single domain antibodies that target the BCMA, from 2021 to 2023 in order to have enough time to examine information submitted about an updated analytical method that was made in response to an FDA information request.

An overall response rate (ORR) of 98% (95% CI, 92.7%-99.7%) and a stringent complete response rate (SCR) of 78% (95% CI, 68.8%-86.1%) were achieved by cilta-cel administered as a single infusion at a dose range of 0.5 to 1.0 x 106 CAR-positive viable T cells per kg of body weight in the phase 1/2 CARITUDE clinical trial (NCT035 The CAR T cells elicited robust and in-depth reactions. The median duration of the response was 21.8 months (95% CI, 21.8 to not estimable) at a median follow-up of 18 months. 

Sundar Jagannath, MD, MBBS, professor of medicine, haematology, and medical oncology at Mount Sinai, served as the principal study investigator. “The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse with fewer patients achieving a deep response as they progress through later lines of therapy,” he said in a press release.

1) The CARTITUDE-1 study’s findings, which showed that cilta-cel can generate deep and durable responses and long-term treatment-free intervals, even in this extensively pretreated multiple myeloma patient population, have piqued my interest because of this. The approval of Carvykti today fills a critical need for these patients.

97 individuals with relapsed/refractory multiple myeloma were the subject of the open-label, single-arm, multi-center CARITUDE study. The percentage of patients who experienced adverse events (AEs) and the percentage who experienced severe AEs served as the phase 1 coprimary end points. ORR served as the phase 2’s main finish point. The researchers examined progression-free survival (PFS), overall survival (OS), time to response, levels of CAR-T cells, levels of BCMA-expressing cells, levels of soluble BCMA, systemic cytokine concentrations, levels of BCMA, health-related quality of life, and change from baseline health-related quality of life as secondary end points.

The study’s two-year follow-up findings were recently reported at the annual meeting of the American Society of Hematology. According to the data, in terms of effectiveness, the median time to first reaction was 1 month, and the median time to complete response or better was 2 months (range, 1-15). When the presence of minimum residual disease (MRD) in 57 patients was assessed, 91.8% of them tested negative. The PFS rate was 66.0% (95% CI, 54.9%-75.0%) and the OS rate was 80.9% (95% CI, 71.4%-87.6%) at the 18-month timepoint. The PFS rate was 96.3% and the OS rate was 100% in the group of patients who had sustained MRD for more than 6 months and more than 12 months. PFS median was not attained.

2) Neutropenia (94.8%), anaemia (68.0%), leukopenia (60.8%), thrombocytopenia (59.8%), and lymphopenia (49.5%) were among the grade 3/4 hematologic adverse events that were seen. 94.8% of patients had cytokine release syndrome, which predominately occurred in grades 1 and 2.

The FDA-approved label for cilta-cel lists Guillain-Barré syndrome, peripheral neuropathy, cranial nerve palsies, and hemophagocytic lymphohistiocytosis in addition to the frequent grade 3/4 AEs.

The FDA gave cilta-cel breakthrough and orphan drug designations prior to approving it for the treatment of patients with relapsed or refractory multiple myeloma who had received four or more prior lines of therapy. Cilta-cel has also been submitted for approval under this indication in Europe.

How Cilta-Cel therapy works ?

Cilta-Cel therapy CAR T-cell therapy, or chimeric antigen receptor treatment, is a new type of immunotherapy that uses specially engineered T cells to more precisely target cancer cells. The immune system is made up of cells and organs that work together to keep the body safe from infection and cancer. T cells are one type of cell that hunts down and kills aberrant cells, including cancer cells. Because cancer cells can sometimes elude the immune system, it is necessary to retrain the immune system to recognise and fight cancer cells. CAR T-cell therapy is a novel way of training the immune system to fight cancer.

After a sample of a patient’s T cells is taken from the blood, the cells are re-engineered to have specific structures on their surface called chimeric antigen receptors (CARs). The receptors on these CAR T cells may aid the T cells in identifying and attacking cancer cells throughout the body when they are reinjected into the patient.

CAR T-cell therapy is now licensed by the FDA as the standard of care for certain types of relapsed or refractory Non-Hodgkin lymphoma, multiple myeloma, and pediatric relapsed acute lymphoblastic leukaemia (ALL), and is being tested in additional types of blood cancer.

CAR T-Cell therapy is a form of immunotherapy that uses specially modified T-cells which are part of our immune system to fight cancer. A sample of patients T cells are collected from the blood, then it is modified to produce special structures called chimeric antigen receptors (CAR) on their surface. When these modified CAR cells are re infused in the patient, these new cells attack the specific antigen and kills the tumor cells.

Working of CAR T Cell therapy CAR T Cell therapy in China

What is the cost of Cilta-Cel therapy?

At present Cilta-Cel CAR T-Cell therapy cost around $465,000 USD. Currently it is available in selected centres in US. However, lot of clinical trials are underway in China and its cost is expected to come down significantly once these new trials gets approved.


Side effects of Cilta-Cell (ciltacabtagene autoleucel) therapy

Cilta-Cel (ciltacabtagene autoleucel) may cause side effects that are severe or life-threatening and can lead to death. Call your healthcare provider or get emergency help right away if you get any of the following:

  • fever (100.4°F/38°C or higher)
  • chills or shaking chills
  • fast or irregular heartbeat
  • difficulty breathing
  • very low blood pressure
  • dizziness/light headedness
  • effects on your nervous system, some of which can occur days or weeks after you receive the infusion, and may initially be subtle such as:
    • feeling confused, less alert or disoriented, having difficulty speaking or slurred speech, having difficulty reading, writing and understanding words, memory loss
    • loss of coordination affecting movement and balance, slower movements, changes in handwriting
    • personality changes including a reduced ability to express emotions, being less talkative, disinterest in activities, and reduced facial expression
    • tingling, numbness and pain of hands and feet, difficulty walking, leg and/or arm weakness, and difficulty breathing
    • facial numbness, difficulty moving muscles of face and eyes

Cilta-Cel CAR T-Cell therapy in China

Chinese regulators have granted breakthrough therapy status to Legend Biotech and Janssen’s investigational CAR T-cell therapy, ciltacabtagene autoleucel (cilta-cel), as a potential treatment for relapsed or refractory multiple myeloma.

Cilta-cel refers to both JNJ-4528, which is the name by which the therapy is recognised outside of China, and LCAR-B38M, which is the name by which it is known in China.

The National Medical Products Administration’s (NMPA) Chinese Center for Drug Evaluation (CDE) decision is intended to hasten the development and review of treatments with preliminary clinical evidence of greater promise than current treatments for critical diseases.

According to a press release from Legend, CEO Frank Zhang, PhD, “Breakthrough designation recommended by the China CDE of NMPA signifies a key regulatory milestone in the further development of cilta-cel in multiple myeloma patients.”

He continued, “Legend will continue to explore this investigational therapy in China and abroad in conjunction with Janssen.

The treatment previously held PRIME (PRIority MEdicines) certification from the European Medicines Agency for the same indication and breakthrough therapy designation from the U.S. Food and Drug Administration. Regulatory agencies in the US, EU, Japan, and Korea also classified it as an orphan drug.

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