Promising Results from Arlo-cel CAR T in Myeloma

Bristol-Myers presented interesting results from their CAR-T development product arlocabatagene autoleucel (“arlo-cel”) at the latest annual forum of the American Society of Hematology (ASH). 

What Is Different about Arlo-Cel?

There are currently two FDA-approved treatments available in the US for the treatment of myeloma: Carvykti (Johnson & Johnson) and Abecma (Bristol Myers). Both products target the BCMA protein that is present on myeloma cells. 

Arlo-cel, on the other hand, targets the protein GPRC5D. We already know about GPRC5D from prior posts about the bispecific T-Cell Engager, Talvey (talquetamab; Johnson & Johson).

Arlo-cel may possibly become a “first in class” novel treatment and was recently granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA.

This puts arlo-cel in a class of development products that will receive expedited regulatory review (and, hopefully, future approval).

To understand the early results and the exciting potential future of this product, watch the interview and continue reading below. 

Who Participated in the Arlo-Cel Study? 

86 patients were originally enrolled in the Phase I study (through August 2024) and 79 continued to be drug efficacy evaluable. 

Patients were assigned to 5 groups in the dose escalation phase, and 26 patients were infused with the Recommended Phase II dose of 150 million cells. 

A high percentage of patients fell into the class of “high risk myeloma” with 42% having del (17p) mutations and 36% had extramedullary plasmacytomas.  

In addition, 46% had prior BCMA-targeted therapy that had failed. Noteworthy is the fact that manufacturing of the CAR-T cells was 100% successful, which is a welcome change from other CAR-T cell products on the US market, and good news for patients (especially heavily pre-treated patients).

Early Results

The following data shows the early results of those who participated in the arlo-cell clinical trial. 

Response Rates:

• Overall response rate (ORR): 96%

• Stringent complete response rate (sCR): 42%

• Complete response rate (CR): 4%

• Very Good Partial Response rate  (VGPR): 42%

• Partial Response rate (PR): 8%

Adverse events related to treatment:

• Cytokine Release syndrome (CRS): all were grade 1 or 2, and all were resolved.

• ICANS (neurological toxicity): 10%; all were grade 1 or 2.

• 55% of patients reported skin, nail, and/or oral adverse events, all grade 1 or 2. About half of those patients were resolved during a median period of 55 days.

• Nail events occurred in 35% of patients, but none required treatment.

• Skin events occurred in 26 % of patients. Nearly half of those required no treatment. Others were treated with common products such as nystatin, triamcinolone, and hydrocortisone.

• Minimal residual disease (MRD): 100% of patients with sCR or CR and where MRD data were available reported as MRD-. This means those who responded to the treatment experienced very deep responses in which one in up to a million cells did not include myeloma. 

Efficacy of treatment:

• • The median time it took people to respond to the treatment was 1.0 months.

  • At the time of data cutoff for this data set (late Summer 2024), 74% of patients continued to be monitored in this study. 

  • No patient deaths have been reported so far.

  • Response to treatment continued to deepen over time for 5 % of the patients.

Key Conclusions 

Key conclusions of arlo-cel from this Phase I study are :

• Arlo-cel is safe and with a promising preliminary efficacy in relapsed/refractory myeloma patients with 1-3 prior treatments.

• The treatment has a manageable safety profile.

As this is only a phase 1 trial, more trials are needed to better understand response rates, side effect profiles, and, most importantly, the durability of outcomes. Other clinical trials can explore the combination of this arlo-cel CAR T with other therapies. 

Additional trials with arlo-cel are planned: a Phase II monotherapy study in patients with quadruple drug class exposed disease and a Phase III comparison study in patients who have become refractory to standard Revlimid (lenalidomide) therapy and 1-3 prior lines of therapy. 

These early results are encouraging, and, assuming that further studies continue to bolster the safety and efficacy data sets for arlo-cel, we may be cautiously optimistic that this product may become an additional future treatment option for our disease.

Continue reading breaking news on myeloma research here: HealthTree Myeloma Conference Coverage