Between the 2025 ASCO Annual Meeting and the 2025 EHA Congress, a pair of presentations focused on long-term data from the phase 1b/2 CARTITUTDE-1 trial (NCT02548207) and findings the phase 2 iMMagine-1 trial (NCT05396885), which provided valuable insight in the multiple myeloma field, according to Darren Pan, MD.
CARTITUDE-1 assessed the safety and efficacy of a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of patients with relapsed/refractory multiple myeloma who had previously received at least 3 regimens of systemic therapy. Of note, the 5-year follow-up data presented at the 2025 ASCO Annual Meeting demonstrated that 33% of patients (n = 32/97) who received cilta-cel were treatment- and progression-free at a median follow-up of 61.3 months.1
Although patients in CARTITUDE-1 were treated with cilta-cel in later lines of therapy, Pan emphasized that earlier intervention could be beneficial to some patients. Notably, this was made possible following the April 2024 FDA approval of cilta-cel in patients with relapsed/refractory multiple myeloma after at least 1 prior line of therapy and who are refractory to lenalidomide (Revlimid).2
“One of the ways these findings help frame our approach to the treatment of [patients with] myeloma is that we’re starting to prioritize [treating] patients who are more high-risk, or those who are younger, with CAR T-cell therapy earlier,” Pan explained in an interview with OncLive®. “We know that CAR T-cell therapy has the best chance of success when used in earlier [lines of] treatment.”
During the interview, Pan also discussed the iMMagine-1 trial presented at the 2025 EHA Congress, which evaluated the novel CAR T-cell therapy anitocabtagene autoleucel (anito-cel) in patients with relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy. Data from the study revealed that at a median follow-up of 12.6 months (n = 117), the objective response rate was 97%, including a stringent complete response (CR)/CR rate of 68%. Very good partial response comprised 18% of patients, and partial response comprised 12%.3
Pan is an assistant professor of Medicine at the University of California, San Francisco (UCSF) School of Medicine.
OncLive: What multiple myeloma presentation stood out to you the most at the 2025 ASCO Annual Meeting?
Pan: The first abstract that likely got the most buzz at ASCO was the long-term follow-up of [the] CARTITUDE-1 trial. Essentially, we’ve known since the first publication that cilta-cel is highly effective in patients with late-relapsed multiple myeloma. This is a group that typically has very limited treatment options and a survival of 1 year or a short number of years. [Cilta-cel] really changed the game because it [yielded] high [overall] response rates [and] very durable responses.
The abstract that was presented at ASCO showed that one-third of patients are still in remission 5-plus years after their single one-time infusion of cilta-cel, which was really unheard of before the era of CAR T-cell therapy. What a lot of us myeloma [specialists] are excited about is that we’re starting to see a bit of a tail where the PFS curve plateaus, telling us that it’s possible [for] some of these patients who are still in remission after many years [to] stay in remission for years longer. Maybe, depending on who you ask, [these patients may] potentially be cured of their myeloma, which is something that we won’t know for sure until we continue to follow these patients for years to come.
What do these long-term data with cilta-cel mean for clinical practice?
[CARTITUDE-1 evaluated patients] in the late relapse [setting], but the earlier we seem to move these T-cell redirection therapies, the more effective they are. There are multiple reasons for that. There’s the fact that the myeloma itself is less treatment refractory. There is the fact that the patients’ immune systems have not been exposed to as many chemotherapeutic drugs, so they’re fresher because of those elements.
T-cell redirection therapies seem to work better when the disease burden is well-controlled. It’s easier to do that in the first-line setting or the second-line setting [vs] when they’ve exhausted all of the therapy options. Now we’re seeing that cilta-cel has this really incredible potential to keep patients in remission for a very long period in patients who prioritize the importance of getting long-term remission. In our patients who are diagnosed in their 40s or 50s, for example, getting them to CAR T-cell therapy at the optimal time is something that we’ll likely see more of.
What presentation stood out to you the most at the 2025 EHA Congress?
The one that was the most exciting that paralleled cilta-cel was the iMMagine-1 trial. There’s been a lot of buzz about anito-cel, which was a high bar to clear that cilta-cel set. For many of us, it’s hard to imagine how another BCMA-directed CAR T-cell therapy could fit into the market when we already cilta-cel [and idecabtagene vicleucel (Abecma)], but anito-cel has managed to get a lot of us very excited. The follow-up is still relatively early compared with our approved CAR T-cell therapies, so the jury is still out, but IMmagine-1 showed that with longer follow-up compared with prior publications, it’s achieving similar efficacy to cilta-cel, and with that with time, we’re not seeing some of these delayed neurotoxicities that we saw with longer follow-up with cilta-cel.
There are more common [adverse effects (AEs)], like cranial nerve palsies, that surprisingly, they’ve seen none of out of the over 100 patients treated with anito-cel. However, more top of mind for a lot of us is the fact that we haven’t seen any Parkinsonism, which has become a very well-recognized, although rare, AE of cilta-cel and one that, as a field, we’re still learning how to effectively prevent and manage. With anito-cel, it seems to have the best of both worlds. It has the efficacy that, at least at this early stage, seems comparable to cilta-cel, but without some of these neurologic toxicities. That’s not to say that any of these later toxicities might not still come out as more and more patients are treated. This is still a relatively small sample size of patients, but it’s an exciting initial signal.
What is known so far about late-onset toxicities related to CAR T-cell therapies?
When it comes to late toxicities, neurologic ones are the first ones we generally refer to. Cranial nerve palsies, Parkinsonism, and Guillain-Barré Syndrome are [toxicities] that we can also see in a small number of patients. There has been a lot of research, particularly at UCSF, where our CAR T-cell therapy lead, Anupama Kumar, MD, has evaluated data to show that certain patients, [such as] older patients, are at higher risk of getting some of these late toxicities.
However, aside from neurologic toxicities, the other severe, delayed toxicity that we’re beginning to see is immune effector cell enterocolitis, or essentially, inflammatory diarrhea that we’re seeing occur a couple months after CAR T-cell infusion in a few percentage points of patients, which may not seem particularly significant. [Still,] when patients do get enterocolitis, it can be so severe that they’re having diarrhea 5 [or more] times a day, [and] they can have a lot of difficulty keeping up with their fluid intake. When the diarrhea gets to this level of severity, oftentimes [patients] have difficulty absorbing nutrients because there’s so much inflammation in the gut, and they many even need to be put on parenteral nutrition. In the end, some of these patients die from this complication.
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. However, if anito-cel continues the way it’s going, it may be that we reach for a CAR T-cell therapy that doesn’t seem to have as many of these toxicities in specific patients.
References
- Jagannath S, Martin TG, Lin Y, et al. Long-term (≥5-year) remission and survival after treatment with ciltacelcabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol. Published online June 3, 2025. doi:10.1200/JCO-25-00760
- Carvykti is the first and only BCMA-targeted treatment approved by the U.S. FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. Updated April 6, 2025. Accessed July 9, 2025. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
- Kaur G, Freeman CL, Dhakal B, et al. Phase 2 registrational study of anitocabtagene autoleucel for relapsed and/or refractory multiple myeloma (RRMM): updated results from iMMagine-1. Presented at: 2025 EHA Congress; June 12-15, 2025; Milan, Italy. Abstract S201.
