Janssen Oncology, a Johnson & Johnson company announced the FDA approval of their BCMA-directed multiple myeloma cilta-cel CAR T product. The product brand name will be CARVYKTI™ (pronounced CAR-Vick-TEE) is approved for relapsed or refractory multiple myeloma patients after four or more prior lines of therapy (including a proteasome inhibitor like Velcade, an immunomodulator like Revlimid and a CD38 monoclonal antibody like Darzalex.) 

The story behind the approval is a fascinating one. Legend Biotech (a Chinese company) did the original development on a CAR T product they called LCAR-B38M. The Legend Bio CAR T product made a splash at the June 2017 ASCO conference with impressive results in a clinical trial that involved 35 patients. All (100%) of patients responded to the therapy and 33 out of 35 patients (94%) had clinical remission of multiple myeloma upon receiving the new type of immunotherapy. The data looked so good, that many thought it was too good to be true. 

In December 2017, Janssen announced a partnership with Legend Biotech USA to develop and commercialize the product, naming it ciltacabtagene autoleucel, or cilta-cel for short. 

What is unique about CARVYKTI compared to other CAR T products is that it features two BCMA-targeting antibodies instead of one. Some CAR T approaches are to hit dual targets (like BCMA and SLAM-F7) at the same time. With CARVYKTI hitting two antibodies, that dual different strategy may not be as necessary. 

The approval is based on data from the CARTITUDE-1 study which included patients who had a median of six prior lines of therapy. The study had the following outcomes: 

• Overall Response Rate: 98%
• Stringent Complete Response (for patients who had a response): 78%
• Duration of Response (with median follow-up of 18 months): 21.8 months

The two-year follow-up results recently presented at the American Society of Hematology (ASH) 2021 Annual Meeting showed that 98 percent of patients treated with cilta-cel responded to therapy and a majority of patients achieving sustained depth of response with 83 percent of patients achieving an Stringent Complete Response at the 22-month follow-up.

Sundar Jagannath, MD and 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."

Because CARVYKTI™ is manufactured based on each patients' individual T cells, the treatment requires extensive training, preparation, and certification by the facility 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.

Because patients can experience serious side effects called cytokine release syndrome (CRS), neurotoxicity and low blood counts, the product is only available under a REMS program (Risk Evaluation and Mitigation Strategy). Longer term side effects are being studied from the CARTITUDE-1 study results. 

For more information, go to CARVYKTI.com.

The challenge to date with CAR T therapy has been availability, slowed by the process itself and viral vector availability. Both the Abecma and CARVYKTI™ therapies are in great demand from patients who are relapsing after core myeloma treatment options and patients who are considering this therapy should get on a waiting list. 

This represents a very exciting and hopeful opportunity for myeloma patients who need more powerful options.