AACR 2026: Cilta-cel Shows Rapid, Durable Responses in High-Risk Smoldering Myeloma

By: Wendy LaGrego
Posted: Monday, May 4, 2026

At the 2026 American Association for Cancer Research (AACR) Annual Meeting, Omar Nadeem, of Dana-Farber Cancer Institute, and colleagues, reported results from the phase II CAR-PRISM trial evaluating early use of the B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients with high-risk smoldering multiple myeloma.

The study explores a shift in myeloma management—intervening at a precursor disease stage rather than waiting for progression to symptomatic multiple myeloma. Cilta-cel is already approved in relapsed or refractory multiple myeloma, but its use in high-risk smoldering multiple myeloma aims to deepen responses and potentially achieve curative outcomes.

Study Details

In this single-center trial, 20 patients (median age = 58 years) received a single infusion of cilta-cel at a target dose of 0.3, 0.5, or > 0.5×10⁶ CAR+ T cells/kg following lymphodepleting chemotherapy, without induction or bridging therapy. High-risk disease was defined using established clinical criteria, including the 20/2/20 model. The primary objective focused on safety (particularly dose-limiting toxicities), while secondary endpoints included overall response and measurable residual disease (MRD) negativity.

Key Results

The therapy demonstrated a manageable safety profile. No dose-limiting toxicities were observed during dose escalation. Hematologic adverse events were common but transient, particularly grade 3 to 4 neutropenia. Cytokine-release syndrome was observed in all patients, though it was limited to grade 1 or 2. Neurologic toxicities were seen in a subset of patients, including non–immune effector cell–associated neurotoxicity syndrome events such as tremor or paresthesia, with more complex neurocognitive effects in rare cases. These findings led investigators to refine dosing strategies and incorporate biomarker-guided mitigation approaches, including dose reduction and preemptive corticosteroids in select patients.

At a median follow-up of 12 months, all treated patients achieved MRD negativity at a sensitivity threshold of 10⁻⁶ within 2 months, with responses sustained over time. Among patients with at least 6 months of follow-up, the best overall response rate was 100% complete response. No disease progression or deaths were reported, and patients followed beyond 18 months remained MRD-negative.

These findings suggest that early intervention with CAR T-cell therapy may significantly alter the natural history of high-risk smoldering myeloma.

The study authors concluded: “In this first study of CAR T-cell therapy in a precursor malignancy, cilta-cel induced rapid, deep, and sustained MRD-negative responses in all patients with high-risk smoldering multiple myeloma in the absence of induction therapy. Biomarker-guided mitigation strategies may further optimize neurologic safety.”

DISCLOSURE: For full disclosures of the study authors, visit abstractsonline.com.

AACR Annual Meeting 2026 (Abstract CT013)

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