Arlo-Cel Meets Response End Points in Heavily Pretreated Myeloma

Arlocabtagene autoleucel (arlo-cel; BMS) met its primary end point of overall response rate (ORR) in the registrational phase 2 QUINTESSENTIAL trial (NCT06297226). The trial also met the key secondary end point of complete response rate (CRR) in this population. Additional ORR and CRR end points were met among patients who had received at least 3 prior lines.¹

The manufacturer described the response findings as statistically significant and clinically meaningful. The company characterized the safety profile as consistent with other CAR T-cell therapies and GPRC5D-targeted treatments in multiple myeloma; however, numerical response rates, response durability, progression-free survival, and detailed safety findings from QUINTESSENTIAL were not disclosed.¹

QUINTESSENTIAL Evaluates Treatment After Prior BCMA Therapy

QUINTESSENTIAL is an open-label, multicenter, single-arm study evaluating the efficacy and safety of a single arlo-cel infusion. Quadruple-class exposure was defined as previous treatment with an immunomodulatory drug, a proteasome inhibitor, anti-CD38 therapy, and BCMA-targeted therapy. The study also permitted patients who had previously received CAR T-cell therapy.¹˒²

The primary end point was ORR, defined as a best overall response of partial response or better, in quadruple-class–exposed patients treated with at least 4 previous regimens. Key secondary end points included CRR in this group and response outcomes among quadruple-class–exposed patients who had received at least 3 prior lines.²

This population reflects an emerging clinical challenge. Potent combination regimens are increasingly used earlier in the treatment course, leaving some patients exposed or resistant to several foundational drug classes by the time their disease relapses again. The inclusion of prior BCMA-targeted treatment is particularly important because BCMA-directed CAR T-cell therapies, bispecific antibodies, and antibody-drug conjugates have become central components of the RRMM landscape.¹

GPRC5D Offers an Alternative Cellular Target

Arlo-cel is manufactured using a patient’s own T cells, which are modified to recognize GPRC5D on myeloma cells. The treatment process includes leukapheresis, manufacturing, bridging therapy when needed, lymphodepleting chemotherapy, a single infusion, and postinfusion monitoring.¹

GPRC5D expression is independent of BCMA expression and can be maintained after BCMA-directed treatment, making it an attractive target for patients whose disease has progressed following a BCMA-based therapy. GPRC5D is highly expressed on malignant plasma cells but has more restricted expression in healthy tissues.³

Earlier phase 1 findings established the clinical rationale for advancing arlo-cel. In a dose-escalation and expansion study of 84 patients with RRMM, participants had received a median of 5 prior regimens, and 49% had previously received BCMA-targeted therapy. Among 79 efficacy-evaluable patients, the ORR was 87%, with a 53% complete response rate. Median duration of response was 18 months, median progression-free survival was 18.3 months, and the 1-year overall survival rate was 90%.³

Cytokine release syndrome (CRS) occurred in 82% of phase 1 participants, although most events were grade 1 or 2. Immune effector cell–associated neurotoxicity syndrome occurred in 10%, and other selected neurotoxicities occurred in 12%.

Transient skin, nail, and oral adverse events were also observed, consistent with on-target effects associated with GPRC5D-directed treatment. One death from CRS occurred at the highest evaluated dose.³ These results should not be interpreted as the safety findings from QUINTESSENTIAL, which remain undisclosed.

Pharmacists Will Be Central to Potential Implementation

If arlo-cel advances toward regulatory review, oncology pharmacists will contribute to patient selection, medication reconciliation, lymphodepletion planning, and supportive care. They will also help coordinate bridging therapy during manufacturing and monitor for cytokine release syndrome, neurotoxicity, cytopenias, infections, and GPRC5D-associated adverse effects.

The ongoing randomized phase 3 QUINTESSENTIAL-2 trial (NCT06615479) is comparing arlo-cel with standard regimens in adults with lenalidomide-exposed RRMM.⁴ The study should provide comparative evidence needed to clarify how GPRC5D-directed CAR T-cell therapy could move beyond the most heavily pretreated setting.

For now, the phase 2 announcement shows that QUINTESSENTIAL met its prespecified response end points in patients who had received extensive treatment, including prior BCMA-targeted therapy.

REFERENCES

1. Bristol Myers Squibb. Bristol Myers Squibb announces positive topline results from registrational phase 2 QUINTESSENTIAL trial of arlocabtagene autoleucel. Published September 8, 2026. Accessed September 9, 2026. https://news.bms.com/news/details/2026/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-from-Registrational-Phase-2-QUINTESSENTIAL-Trial-of-the-Potential-First-in-Class-GPRC5D-Directed-CAR-T-Cell-Therapy-Arlocabtagene-Autoleucel----/default.aspx

2. ClinicalTrials.gov. Study of arlocabtagene autoleucel, a GPRC5D-directed CAR T-cell therapy, in adult participants with relapsed or refractory multiple myeloma. NCT06297226. Accessed September 9, 2026. https://clinicaltrials.gov/study/NCT06297226

3. Bal S, Htut M, Nadeem O, et al. Arlocabtagene autoleucel: a GPRC5D-targeted CAR T-cell therapy for heavily pretreated relapsed/refractory multiple myeloma. Blood. 2026;148(10):1240-1250. doi:10.1182/blood.2025030750

4. ClinicalTrials.gov. Study comparing arlocabtagene autoleucel versus standard regimens in adults with relapsed or refractory and lenalidomide-exposed multiple myeloma. NCT06615479. Accessed September 9, 2026. https://clinicaltrials.gov/study/NCT06615479