AdventHealth Cancer Institute Advances the Use of CAR T-Cell Therapy for Multiple Myeloma

The AdventHealth Cancer Institute (AHCI) was the first in Central Florida to offer Carvykti® (ciltacabtagene autoleucel), a chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory multiple myeloma. It is currently available as a second-line treatment, and based on the patient outcomes achieved, AHCI is now participating in the CARTITUDE-5 phase 3 clinical trial to evaluate Carvykti’s efficacy and safety as a frontline therapy for newly diagnosed multiple myeloma. CAR-T therapies like Carvykti hold the potential to reduce treatment burden through a one-time infusion that can lead to long-lasting remission, eliminating the need for ongoing, repetitive treatments.

“We were pioneers in offering cell therapy and continue to stay on the forefront, offering CAR-T treatments both in the clinical trial as well as the commercial FDA-approved space,” shares AHCI’s Medical Director of Stem Cell Transplant and Cellular Therapy Rushang Patel, MD, PhD. “We began offering Carvykti in 2022, soon after it became commercially available, and are excited about our involvement in the latest clinical trial. With cancer, we are always striving toward a cure and with innovative treatments like Carvykti, we believe we are getting closer to making that goal a reality for our patients with multiple myeloma.”

Improving Outcomes for Multiple Myeloma
Five-year follow-up data from the original phase 1b/2 CARTITUDE-1 study of Carvykti in patients with heavily pretreated (three or more lines of treatment) relapsed/refractory multiple myeloma were recently presented at the American Society of Clinical Oncology (ASCO) conference and revealed that five years after a single infusion, one-third of patients achieved treatment-free and relapse-free survival.

“These kinds of remarkable results have never been seen before in such heavily treated patients,” asserts Dr. Patel. “Investigators are even beginning to wonder if there is a chance of cure with this treatment.”

Additionally, the randomized phase 3 CARTITUDE-4 study compared Carvykti to physician’s choice of two standard treatments in patients with lenalidomide-refractory multiple myeloma who had received one to three lines of therapy. It found that at 12 months, 75.9% who received Carvytki achieved progression-free survival compared to 48.6% in the standard-care group. More patients in the Carvykti group had an overall response and even tested negative for minimal residual disease (MRD), the most sensitive assessment of their cancer. This resulted in FDA approval of Carvykti as a second-line treatment in April 2024.

“So now, once a patient fails their initial treatment, we can offer Carvykti, and that’s where we are seeing a lot of patients going into minimal residual disease, which means they don’t even have one myeloma cell in a million cells,” explains Dr. Patel. “At AdventHealth, we have also been on the forefront of adopting the next-generation sequencing technology to measure MRD in our patients so now we can combine a super powerful treatment with the ability to detect and quantify tiny numbers of cells. This provides us with deeper insight to guide new and future treatment strategies.”

Overcoming Challenges in Treating Multiple Myeloma
A hematologic cancer, multiple myeloma is characterized by a proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Traditionally, the three main classes of drugs used to treat it have included proteasome inhibitors, immunomodulatory drugs (IMiDs) and monoclonal antibodies. Stem cell transplant is another treatment option but is contraindicated for those of advanced age, frailty or with severe heart, kidney or lung disease. Historically, multiple myeloma has proven challenging to treat with these standard-of-care therapies because of frequent relapses due to drug resistance, disease complications that can be difficult to manage, and limited treatment options available for elderly and frail patients with comorbidities.

“These patients often undergo years of treatment,” says Dr. Patel. “In addition to its effectiveness, the beauty of a CAR-T therapy like Carvykti is that it’s ‘one and done,’ and if a patient goes into remission, they get a treatment holiday, which significantly improves their quality of life. In addition, it is tolerated by a wider range of patients, including those who are not candidates for stem cell transplant. We are even able to do CAR-T for patients in their 80s if their overall health is good.”

How Carvykti Works
Carvykti (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T-cell immunotherapy. A personalized medicine delivered through a one-time infusion, it works by redirecting the patient’s T cells to recognize and attack a target on the surface of multiple myeloma cells.

The entire treatment process generally takes about two to three months:

• The patient’s blood is collected through leukapheresis.
• The white blood cells are sent to a manufacturing center to make the Carvykti, which typically takes four to five weeks.
• While the Carvykti is being made, patients may receive other multiple myeloma treatments to help prevent disease progression.
• Prior to receiving the Carvykti infusion, the patient will receive lymphodepletion chemotherapy for three days to prepare their body for the CAR-T therapy. This helps prevent rejection of the CAR T-cells.
• The Carvykti infusion itself takes about 30-60 minutes.
• Patients are carefully monitored for 2 weeks after the infusion.

Leading the Way in Addressing Safety and Cost Challenges of CAR-T Therapy

Like other CAR-T therapies, the primary adverse effects associated with Carvykti include cytokine release syndrome (CRS) and neurotoxicity. Dr. Patel emphasizes the importance of identifying and managing symptoms early to stop them from progressing.

“That’s where it is important to have a good care team that picks up on those side effects immediately and can intervene,” he comments. “So far, looking at our own internal data, we are doing very well at managing side effects – on par or even better than what has been published in the literature.”

The expense of CAR-T can also create challenges, but Dr. Patel and his team at AHCI continually work to reduce the overall cost of treatment. One of the primary ways AHCI has been able to make CAR-T more affordable is by performing it in an outpatient setting, avoiding the higher expense of hospitalization while also making care more convenient for patients.

“We are now able to do CAR-T therapies like Carvykti safely and more cost effectively on an outpatient basis, and other institutions around the country are looking to us as a model for this,” mentions Dr. Patel. “In September, I was invited to a conference organized by the Mayo Clinic to present our approach, and over the summer, my colleague Dr. Arlene Gayle gave a similar lecture at the International Myeloma Society meeting. Both presentations were well received with a lot of ‘aha’ moments from those in attendance.”

An Ongoing Commitment to Advancing Cell Therapies

In addition to the current CARTITUDE-5 study that is exploring if Carvykti can safely and effectively be used earlier in the treatment paradigm for multiple myeloma, AHCI is participating in additional clinical trials examining the next generation of CAR T-cells. They are also looking beyond T-cells into natural killer (NK) cell therapies.

“For the first time in the history of myeloma, we are coming closer to a cure,” says Dr Patel. “Every step of the way, we are striving to stay ahead of the game and bring the latest CAR-T treatments to our patients. For example, while Carvykti targets one antigen on the myeloma cell, the next generation CAR-T therapies under investigation target two antigens to further reduce the ability of cancer cells to escape. We are committed to continue offering these types of clinical trials at AdventHealth for the benefit of our patients.”

To refer a patient for evaluation for Carvykti or one of the other CAR-T therapies available at AHCI, contact the AdventHealth Stem Cell Transplant and Cellular Therapy program at Call407-303-2070.