Arlo-Cel Produces Deep Responses in Pretreated R/R Multiple Myeloma

The investigational GPRC5D-targeting CAR T-cell therapy arlocabtagene autoleucel (arlo-cel) elicited high, enduring responses among patients with previously treated relapsed/refractory multiple myeloma, according to a presentation on findings from a single cohort in a phase 1 study (NCT04674813) at the European Hematology Association (EHA) 2026 Congress.

A single infusion of arlo-cel produced an overall response rate (ORR) of 94% among 31 evaluable patients, which included a complete response (CR) or better in 71%. Additionally, the median time to response (TTR) was 0.99 months (IQR, 0.95-1.68), and the 18-month duration of response (DOR) rate was 64.6%. Among 20 patients with evaluable minimal residual disease (MRD), the MRD-negative CR rate was 65% (95% CI, 40.8%-84.6%).

Additional efficacy data revealed a progression-free survival (PFS) rate of 73.0% (95% CI, 53.2%-85.5%) at 12 months and 62.6% (95% CI, 42.7%-77.3%) at 18 months. Furthermore, the overall survival (OS) rate was 100% (95% CI, 100%-100%) at both 12 and 18 months.

“Arlo-cel cell demonstrated deep and clinically meaningful responses after a single infusion, with an ORR of 94%, a CR rate of 71%, an 18-month PFS rate of 63%, and OS [rate] of 100%,” study investigator Susan Bal, MD, from the University of Alabama at Birmingham, in Birmingham, Alabama, stated in the presentation. “These results support arlo-cel as a potentially effective early-line treatment option in patients with relapsed and refractory multiple myeloma.”

In cohort C of this first-in-human phase 1 study, patients with 1 to 3 prior lines of treatment for relapsed/refractory multiple myeloma were assigned to receive arlo-cel at the recommended phase 2 dose of 150 x 10⁶ CAR T cells following lymphodepleting chemotherapy.

The trial’s primary end point was safety and tolerability. Secondary end points included ORR, CR rate, DOR, and TTR based on International Myeloma Working Group criteria; PFS; and OS. MRD-negative status and pharmacodynamics were assessed as exploratory end points.

Patients 18 years and older with relapsed/refractory multiple myeloma at no more than 12 months after completing the most recent line of therapy and an ECOG performances status of 0 or 1 were eligible for enrollment on the trial. Having 1 to 3 prior lines of treatment, including a proteasome inhibitor and an immunomodulatory agent, was another requirement for study entry.

The median patient age was 62.0 years (range, 31-78), and most were male (67.7%) and White (67.7%). Of note, patients received a median of 2 (range, 1-3) prior lines of treatment, and 29.0% received 3 prior lines. Additionally, most patients had refractory disease following lenalidomide (Revlimid; 90.3%).

Arlo-cel appeared to be well tolerated among patients; investigators observed no new safety signals. Treatment-emergent adverse effects (TEAEs) of any grade and grade 3/4 occurred in 100% and 87.1% of patients, respectively. The most common hematologic TEAEs of any grade included neutropenia (83.9%), thrombocytopenia (71.0%), and anemia (45.2%). Additionally, the most common non-hematologic TEAEs included hypocalcemia (41.9%), hyperglycemia (38.7%), and dysgeusia (35.5%). Of note, 61.3% of patients experienced infections.

There were no grade 3 or higher treatment-related AEs (TRAEs) of special interest such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS occurred in 83.9% and 9.7% of patients, respectively.

Select on-target, off-tumor (OTOT) events were typically grade 1/2, and most events resolved. OTOT events of note included skin (25.8%), oral (41.9%), nail (38.7%), and weight loss (3.2%).

Disclosures: Bal noted receiving consultancy/honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Janssen, Kite/Arcellx, and Pfizer. She also noted receiving researching funding from AbbVie, BeiGene, Bristol Myers Squibb, Fate Therapeutics, and Pfizer.

Reference

Bal S, Htut M, Berdeja J, et al. Arlocabtagene autoleucel, a GPRC5D-targeted CAR T-cell therapy for patients with relapsed/refractory multiple myeloma: updated phase 1 safety and efficacy results in patients with 1-3 prior regimens. Presented at: European Hematology Association 2026 Congress; June 11–14, 2026; Stockholm, Sweden. Abstract S200.