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U.S. FDA approves medicine for the treatment of relapsed or refractory multiple myeloma

The Janssen Pharmaceutical Companies of Johnson & Johnson and its China-focused partner Legend Biotech Corp. developed a therapy to treat a type of white blood cell cancer, which was approved by the FDA on Monday.

Approval is primarily based on the pivotal phase 1b/2 CARTITUDE-1 study, which demonstrated an overall response rate (ORR) of 98 percent in patients with refractory or relapsed multiple myeloma after four or more prior lines of therapy including proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody.

CARVYKTI™ is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies. In the pivotal CARTITUDE-1 study, one-time treatment with ciltacabtagene autoleucel resulted in deep and durable responses, with 98 percent (95 percent Confidence Interval [CI], 92.7-99.7) of patients with RRMM responding to therapy (98 percent overall response rate [ORR] (n=97). Notably, 78 percent (95 percent CI, 68.8-86.1) of the patients achieving this level of response (n=76) experienced a stringent complete response (sCR), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment. At a median of 18 months follow-up, the median duration of response (DOR) was 21.8 months.

CARVYKTI™ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI™ REMS Program. The Safety Information for CARVYKTI™ includes a Boxed Warning regarding Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and prolonged and/or recurrent cytopenias. Warning and Precautions include prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, and effects on the ability to drive and use machines. The most common adverse reactions (≥20 percent) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC., said:

We are committed to harnessing our science, deep disease understanding, and capabilities to bring forward cell therapies like CARVYKTI as we continue to focus on our ultimate goal of delivering a cure for multiple myeloma.We extend our sincere gratitude to the patients, their families, and the teams of researchers and study centers who have participated in the clinical study of CARVYKTI and enabled today’s approval.

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. Despite the development of additional treatment options in recent years, most people living with multiple myeloma face poor prognoses after experiencing disease progression following treatment with three major therapy classes, which include an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Sundar Jagannath, M.D., Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and principal study investigator, said:

The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up. The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time.

As a personalized medicine, CARVYKTI™ treatment requires extensive training, preparation, and certification to ensure a positive experience for patients. Through a phased approach, Janssen and Legend Biotech will activate a limited network of certified treatment centers as the company works to scale its production capacity and increase the availability of CARVYKTI™ throughout the U.S. in 2022 and beyond, to ensure that we can provide CARVYKTI™ treatment to oncologists and their patients in a reliable and timely manner.

Mathai Mammen, M.D., Ph.D., Executive Vice President, Pharmaceuticals, Janssen Research & Development, LLC, Johnson & Johnson, said:

This approval of Janssen’s first cell therapy is a testament to our continuing commitment in oncology to deliver new therapeutic options and drive toward our vision of the elimination of cancer. Today’s approval underscores our determination to develop therapies that can help patients living with what remains an intractable blood cancer today and at the same time offer hope for the future.


The longer-term efficacy and safety profile of ciltacabtagene autoleucel is being assessed in the ongoing CARTITUDE-1 study. Two-year follow-up results recently presented at the American Society of Hematology (ASH) 2021 Annual Meeting.


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