iMMagine-1 vs CARTITUDE-1 MAIC Shows Comparable Efficacy, Improved Safety With Anito-Cel in Relapsed/Refractory Multiple Myeloma

Anitocabtagene autoleucel (anito-cel) showed a favorable safety profile with efficacy comparable to that of ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with relapsed and/or refractory multiple myeloma (RRMM) who had received 4 or more prior lines of therapy, according to data from a matching-adjusted indirect comparison (MAIC) presented at the 23rd International Myeloma Society (IMS) Annual Meeting & Exposition.¹ Because no head-to-head trial has compared the 2 B-cell maturation antigen (BCMA)-directed CAR T-cell therapies, investigators used an unanchored MAIC to weight patient-level outcomes from the phase 2 iMMagine-1 trial (NCT05396885) of anito-cel against published and regulatory data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) of cilta-cel, adjusting for baseline prognostic factors identified by an expert clinical panel.

In the weighted analysis, overall response rates were statistically similar between anito-cel and cilta-cel (96% [n = 112 of 117] vs 98% [n = 95 of 97]; OR, 0.34; 95% CI, 0.06-1.89), as were rates of complete response (CR) or better (74% vs 78%; OR, 0.75; 95% CI, 0.39-1.45) and very good partial response (VGPR) or better (88% vs 95%; OR, 0.37; 95% CI, 0.12-1.11). None of the efficacy comparisons reached statistical significance (anito-cel, n = 117; cilta-cel, n = 97; effective sample size after weighting for the anito-cel efficacy population, 103).

How was the comparison conducted?

Anito-cel is an investigational BCMA-directed CAR T-cell therapy built on a novel D-domain binder and designed for durable efficacy with a favorable safety profile; it is under evaluation in iMMagine-1, an efficacy-evaluable population of 117 patients with a median follow-up of 15.9 months. Cilta-cel uses a camelid-derived, heavy chain-only binder and has been available as a standard-of-care option in the United States and other countries for 4 years; the CARTITUDE-1 population used for comparison totaled 97 patients with a median follow-up of 18 months, drawn primarily from the FDA approval publication.

Because the trials were not randomized against each other, investigators built comparator evidence from a systematic literature review and regulatory documents, prioritizing FDA sources, and reweighted the iMMagine-1 population to match CARTITUDE-1 on high-priority prognostic factors and effect modifiers identified by an expert panel. Unweighted, the anito-cel population skewed somewhat older (age ≥65, 49.6% vs 36.1%) and had more extramedullary disease (17.9% vs 13.4%) and high-risk cytogenetics (35.9% vs 23.7%) than the cilta-cel population, while rates of triple-refractory (46.2% vs 45.4%) and penta-refractory (41.0% vs 42.3%) disease were similar between the 2 groups. After weighting, the effective sample size was 103 for the efficacy comparison and 106 for the safety comparison.

What did the safety comparison show?

Anito-cel was associated with significantly lower rates of several toxicities relative to cilta-cel. Any-grade cytokine release syndrome (CRS) occurred in 85% of anito-cel–treated patients vs 95% of cilta-cel–treated patients (OR, 0.33; 95% CI, 0.11-0.94), and any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 8% vs 23% (OR, 0.28; 95% CI, 0.12-0.67); grade 3 or higher CRS (1% vs 5%) and ICANS (1% vs 5%) trended lower with anito-cel but were not statistically significant. Grade 3/4 infections were less frequent with anito-cel (9% vs 23%; OR, 0.28; 95% CI, 0.12-0.65), as was non-relapse mortality (3% vs 11%; OR, 0.20; 95% CI, 0.06-0.68). Grade 3 or higher adverse effects (AEs) of any type occurred less often with anito-cel (85% vs 100%; risk difference, −14.53%; 95% CI, −20.92% to −8.14%; P < .001), though all patients in both cohorts experienced an AE of some grade.

The most notable difference was in non-ICANS neurotoxicity: no cases of any grade occurred among the 117 anito-cel–treated patients, compared with 12 cases (12.4%) among the 97 cilta-cel–treated patients (risk difference, −12.37%; 95% CI, −18.99% to −5.75%; P < .001), including 9 cases (9.3%) of grade 3 or higher (risk difference, −9.28%; 95% CI, −14.56% to −4.00%; P < .01). Within this category, parkinsonism occurred in 0 anito-cel–treated patients vs 5 cilta-cel–treated patients (5.2%; risk difference, −5.15%; 95% CI, −9.60% to −0.71%; P = .02), and cranial nerve palsy occurred in 0 vs 3 patients (3.1%; risk difference, −3.09%; 95% CI, −6.57% to 0.39%; P = .08, not significant).

“In this matching-adjusted indirect comparison using variables that were identified from an expert panel, anito-cel had a superior safety profile in terms of all-grade CRS, all-grade ICANS, non-relapse mortality, and severe infections, while efficacy was comparable. Very importantly, there were no cases of non-ICANS neurotoxicity seen with anito-cel,” said Surbhi Sidana, an associate professor of medicine at Stanford University in California.

What are the limitations, and what comes next?

Sidana noted 2 key limitations. First, the iMMagine-1 and CARTITUDE-1 trials enrolled patients in different eras, during which supportive-care guidelines for managing CRS, ICANS, and related toxicities have evolved, which could affect the comparability of safety outcomes across trials. Second, ferritin, which was identified by the expert panel as a high-priority prognostic variable, could not be incorporated into the weighting because it was not reported in the CARTITUDE-1 comparator data, leaving that potential confounder unadjusted.

Despite those caveats, the investigators concluded that anito-cel demonstrated a distinct benefit-risk profile relative to cilta-cel, with safety differences that may factor into clinical decision-making and could potentially reduce downstream health care resource utilization in later-line RRMM. Anito-cel remains investigational; iMMagine-1 is ongoing, and additional prospective and real-world comparative data will be needed to confirm these indirect findings as anito-cel moves toward potential approval.

Reference

1. Sidana S, Martin T, Ting J, et al. Matching-adjusted indirect comparisons (MAICs) of efficacy and safety outcomes for anitocabtagene autoleucel versus ciltacabtagene autoleucel in 4L+ relapsed and/or refractory multiple myeloma (RRMM). Presented at: 23rd International Myeloma Society Annual Meeting & Exposition; September 23-26, 2026; Glasgow, Scotland. Abstract PA-298.