Darren Pan, MD, is an assistant professor of Medicine at the University of California, San Francisco School of Medicine.

Dr Pan on Late-Onset Toxicities Associated With CAR T-Cell Therapy in Multiple Myeloma

"Between the delayed neurotoxicity and the delayed enterocolitis, those are likely the most significant toxicities, albeit rare. They are ones that we're trying to learn more about, both in terms of pathogenesis and clinical management. Hopefully, in the coming years, we will be better equipped to prevent and manage these AEs that we're seeing from CAR T-cell therapy"

Darren Pan, MD, assistant professor of Medicine at the University of California, San Francisco (UCSF) School of Medicine, described key late-onset toxicities associated with CAR T-cell therapies in patients with multiple myeloma.

Late-onset neurologic toxicities are among the most commonly observed delayed complications. These include cranial nerve palsies, Parkinsonism, and Guillain-Barré Syndrome, all of which have been reported in a minority of patients, Pan began. He noted that ongoing research at UCSF Health has identified older age as a potential risk factor for developing these delayed neurologic events following CAR T-cell therapy.

In addition to neurotoxicity, immune effector cell enterocolitis has emerged as a severe but rare complication, manifesting as inflammatory diarrhea that can occur several months after treatment, Pan continued. Although the incidence is low, the clinical significance of this toxicity, which may present with 5 or more episodes of diarrhea per day and lead to dehydration, malabsorption, and, in severe cases, the need for parenteral nutrition, Pan underscored. Some patients may experience life-threatening complications related to enterocolitis, he added.

Both delayed neurotoxicity and enterocolitis are areas of active investigation, particularly with regard to pathogenesis and optimal management strategies, Pan emphasized. As clinical experience with CAR T-cell therapy expands, understanding and mitigating these late toxicities remains a priority. Of investigational agents such as anitocabtagene autoleucel continue to demonstrate favorable toxicity profiles, they may offer a preferred option in patients at risk for these late adverse effects, Pan concluded.

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Darren Pan, MD, outlines late-onset toxicities related to CAR T-cell therapies in multiple myeloma and their management.
 

Darren Pan, MD, highlights the novelty of anito-cel in relapsed/refractory multiple myeloma, including the difference in safety profile vs cilta-cel.

Dr Pan on the Novel Therapy Anito-Cel in Relapsed/Refractory Myeloma

“At EHA, the one [abstract] that was the most exciting, parallel with cilta-cel was the iMMagine-1 trial. There’s been a lot of buzz about anito-cel, which had a high bar to clear than cilta-cel.”

Darren Pan, MD, an assistant professor of Medicine at the University of California, San Francisco School of Medicine, highlighted the novelty of anitocabtagene autoleucel (anito-cel; CART-ddBCMA) for the treatment of patients with relapsed/refractory multiple myeloma.

Data from the phase 2 iMMagine-1 trial (NCT05396885) revealed that in 117 patients with relapsed/refractory multiple myeloma, the overall response rate was 97%, which included a stringent complete response (sCR)/CR rate of 68%. Of note, 93% (n = 70/75) were negative for minimal residual disease at a minimum sensitivity of 10

. Furthermore, the 6- and 12-month progression-free survival rates were 91.9% (95% CI, 85.0%-95.7%) and 79.3% (95% CI, 68.6%-86.7%), respectively. Additionally, the respective overall survival rates at 6 and 12 months were 96.6% (95% CI, 91.1%-98.7%) and 95.2% (95% CI, 88.7%-98.0%), respectively.

A parallel to ciltacabtagene autoleucel (cilta-cel; Carvykti), of which long-term follow-up is notably being evaluated in the phase 1b/2 CARTITUDE-1 trial (NCT03548207), anito-cel has garnered attention in the multiple myeloma landscape, Pan began. He noted that cilta-cel has gained traction in the space and has set a high bar for other CAR T-cell therapies, including anito-cel, following its established efficacy and safety data.

However, anito-cel has also grabbed some attention, especially after updated data were presented at the 

2025 European Hematology Association Congress

, Pan said. Although the follow-up for anito-cel is early compared with cilta-cel, he emphasized that anito-cel has demonstrated similar efficacy to cilta-cel and with a significant difference in terms of safety profile. In particular, with longer follow-up, delayed neurotoxicities have not been observed at a high rate compared with cilta-cel, he noted. Even common adverse effects (AE), such as cranial nerve palsies, were not reported in patients treated with anito-cel, Pan asserted. Notably, signs of Parkinsonism have not been observed, which has been acknowledged as a rare AE associated with cilta-cel infusion, he said. Still, there could be chances of later-onset toxicities as more patients begin to receive anito-cel, Pan concluded.

Darren Pan, MD

Articles

Dr Pan on Late-Onset Toxicities Associated With CAR T-Cell Therapy in Multiple Myeloma

Dr Pan on the Novel Therapy Anito-Cel in Relapsed/Refractory Myeloma