Arlo-Cel Delivers High, Durable Responses With Manageable Safety in R/R Myeloma

The GPRC5D-targeted CAR T-cell therapy arlocabtagene autoleucel (arlo-cel) could represent a key treatment option for patients with relapsed/refractory multiple myeloma, including those who have been exposed to prior BCMA-directed therapies, according to Omar Nadeem, MD.

Arlo-cel produced high and durable response rates with a favorable safety profile in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy, according to findings from the phase 1 trial (NCT06121843) presented at the 22nd Annual International Myeloma Society Meeting and Exposition.1

At a median follow-up of 18.3 months (range, 3.8-24.3), the overall response rate (ORR) was 94%, including a 71% complete response (CR) rate. Minimal residual disease (MRD) negativity was achieved in 56.3% of evaluable patients, all of whom attained MRD-negative CRs. Median progression-free survival (PFS) was 24.3 months (95% CI, 12.5-not reached).

In an interview with OncLive®, Nadeem, medical oncologist at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, discussed the updated efficacy and safety data for arlo-cel, the significance of these findings in the context of current CAR T-cell therapy development, and the ongoing phase 3 trial comparing arlo-cel with standard-of-care regimens in earlier-line multiple myeloma.

OncLive: What was the rationale for investigating arlo-cel as a GPRC5D-targeted CAR T-cell therapy in multiple myeloma?

Nadeem: [Arlo-cel was] previously studied in patients who had 3 or more lines of therapy in [in the first part of the] phase 1 study, and it demonstrated a high ORR, including in patients who had prior BCMA therapy. This cohort [of patients who received 1 to 3 prior lines of therapy] is a subset within the phase 1 study that’s evaluating Arlo-cel in patients who had earlier lines of therapy. The goal here was to see if early administration of Arlo-cel, which targets GPRC5D, can lead to the same deep and durable responses in patients with relapsed/refractory myeloma.2

What was the study design and key eligibility criteria for this phase 1 trial?

Patients were eligible for this [portion of the] study if they had 1 to 3 prior lines of therapy. Prior BCMA-targeted therapy was also allowed.

Patients received Arlo-cel at a dose of 1.5 x 106 cells. Despite this being an earlier-line cohort, the median number of prior therapies was 2. This was a fairly refractory population despite being in earlier lines.

What efficacy and safety signals did the study demonstrate with arlo-cel in patients with relapsed or refractory multiple myeloma?

Cytokine release syndrome [CRS] occurred in 84% of patients, but no grade 3 or higher CRS was observed, which was reassuring. Neutropenia occurred in 84% of patients—but all cytopenias ultimately resolved. Infection rates were relatively low, with 55% of patients experiencing infections and no grade 3 or higher [infections] reported.

GPRC5D as a target is associated with certain on-target, off-tumor effects, including dysgeusia, skin changes, and nail-bed changes.] These effects were observed in approximately one-third of patients but were transient and did not persist. Two patients experienced neurotoxicities, including ataxia and gait disturbances, which were grade 2 or less and ongoing at the data cutoff after approximately 18 months of follow-up.

The efficacy results were excellent. Ninety-four percent of patients responded to therapy, with a CR rate of 71%. Responses deepened over time. At 1 year, approximately 75% of patients remained in response, and 62% of responders maintained ongoing responses at the time of data cutoff. These findings indicate encouraging activity and a favorable safety profile.

What do these findings indicate about the future role of arlo-cel within the multiple myeloma treatment landscape?

Currently, we have several BCMA-directed CAR T-cell therapies approved, as well as several BCMA-directed bispecific antibodies.] However, there is only one GPRC5D-targeting agent approved—[talquetamab-tgvs (Talvey), a bispecific antibody].

Thus, there remains an unmet need for a CAR T-cell therapy targeting this antigen, which has shown strong efficacy. Some of the AEs seen with GPRC5D targeting are transient, suggesting that this therapy could provide an important new option for patients who need a CAR T-cell therapy directed at a different antigen.

Reference

Bal S, Htut M, Berdeja JG, 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 the 22nd International Myeloma Society Annual Meeting; Toronto, Canada, September 17-20, 2025. Poster PA-080