CAR T-Cell Therapy in Multiple Myeloma: Managing Adverse Effects Through Collaboration

As part of the Tox Check series, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Caitlin Costello, MD, of UC San Diego Health, and Joshua Richter, MD, of Mount Sinai, to discuss the available CAR T-cell therapies for multiple myeloma, including ide-cel and cilta-cel. The panel explored the adverse effects of treatment, identified management strategies, and explained the importance of collaboration between community and academic oncologists to produce the best possible outcomes for patients.

“Communication is absolutely essential,” Dr. Richter said. “Some of the toxicities we understand reasonably well, but others we’re still learning about.”

Idecabtagene Vicleucel and Ciltacabtagene Autoleucel 

In the past few years, significant progress has been made regarding the use of CAR T-cell therapies in multiple myeloma. Initially approved in 2021 for fifth-line treatment and beyond, ide-cel received expanded approval for third-line treatment. Cilta-cel, first greenlit for later lines of therapy, is now approved for the second line and beyond.

Although Dr. Rohit Gosain called the news “very exciting,” he said the reality is that just a small number of patients in the community are exposed to these options. He said he hopes that through these discussions, physicians become “a bit more comfortable talking about these modalities so that our patients can get the best care close to home.”

A large part of the conversation centered on the adverse effects of CAR T-cell therapies. The two most commonly seen in the community setting are CRS and ICANS, according to Dr. Richter. CRS occurs more often than ICANS and is “reasonably predictable,” he said, adding that CRS usually presents about 6 to 8 days after CAR T-cell administration and can be treated with tocilizumab (an interleukin-6 receptor antagonist).

Immunosuppression and IVIG Therapy

Another key factor is immunosuppression, which occurs often in patients treated with cilta-cel. CAR T-cell therapy can deplete B cells, T cells, and plasma cells, “leaving patients without a lot of protection,” Dr. Costello said. She recommended starting patients on IVIG immediately following CAR T-cell therapy.

She advised continuing IVIG as long as 6 months to allow patients’ immune systems to recover. “This is critical. We need to be aggressive with antiviral prophylaxis,” she said, urging providers to keep an open line with academic institutions regarding which medications they recommend and for how long. “That communication is key.”

Rare Adverse Effects: Cytomegalovirus, Enterocolitis, and Parkinsonism

Additional adverse effects associated with CAR T-cell therapy are somewhat rare but still merit careful consideration, such as CMV reactivation, according to Dr. Richter. If a patient has had normal cytokine counts and then they start dropping, “something’s a little bit off,” a broader workup is needed, he said.

Another rare adverse effect, enterocolitis, has been a head-scratcher. “We still don’t have a good understanding of who develops it or when it occurs,” Dr. Richter said. “Colitis-like symptoms after CAR T should never be dismissed. They require aggressive evaluation and close communication” with the treatment center, he said.

In the past, parkinsonism sometimes presented following CAR T-cell therapy, Dr. Richter noted. Although that has become increasingly rare, it’s imperative to remain aware of the symptoms. For example, if a caregiver mentions that a patient has become less talkative or seems off, “we need to take that seriously,” he said.

Any course of treatment involves numerous factors, all of which must be discussed carefully with patients and caregivers, according to Dr. Rohit Gosain. “When we’re deciding which product is appropriate, we need to look at the patient in front of us and understand what their risk tolerance is, what their realistic lifespan is, and what they’re looking for,” he said. “While some patients are hoping for a cure, others are more focused on buying time and may not be strong enough to tolerate the side effects.”

Secondary Malignancies

Even for those who are cured or achieve prolonged remission, monitoring never stops, said Dr. Richter. “Patients can develop secondary malignancies, not necessarily as a result of the therapy, but as a result of living longer,” he said.

For community oncologists, that means ensuring patients continue to get cancer screenings appropriate for their age and sex, while also monitoring complete blood count levels for myelodysplastic syndrome, acute myeloid leukemia, and T-cell malignancies. “If you notice something or your ears perk up, it might be worthwhile to send for flow cytometry,” Dr. Richter said.

This information needs to be communicated to the entire care team, as well as to patients and caregivers, according to the panelists, all of whom emphasized the importance of collaboration throughout the care continuum.

“We need to get comfortable educating our patients on what to expect,” Dr. Rohit Gosain said. “That’s why this discussion is so important.”