Elranatamab Generates Deep and Durable Early Responses in RRMM

Ajay K. Nooka, MD, MPH, FACP

Treatment with erlanatamab (PF-06863135) led to early, deep, and durable responses among patients with relapsed/refractory multiple myeloma (RRMM) who received prior treatment with a BCMA-directed therapy.¹

Findings come from a pooled analysis of patients from studies in the MagnetisMM program, including the phase 1 MagnetisMM-1 (NCT03269136), phase 1 MagnetisMM-2 (NCT04798586), phase 2 MagnetisMM-3 (NCT04649359), and phase 2 MagnetisMM-9 (NCT05014412) trials.

At a median follow-up of 11.3 months (range, 0.3-32.3), patients who were given elranatamab after any prior BCMA-directed therapy (n = 87) reached an overall response rate (ORR) of 46% (95% CI, 35.2%-57.0%). This included a stringent complete response (sCR) rate of 4.6%, a complete response (CR) rate of 13.8%, a very good partial response (VGPR) rate of 24.1%, and a partial response (PR) rate of 3.4%.

For patients treated with a prior BCMA-directed antibody-drug conjugate (ADC; n = 59), the ORR was 42.4%. The sCR rate was 5.1%, CR was 13.6%, VGPR was 20.3%, and PR rate was 3.4%, respectively. Then, patients who received treatment with a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy (n = 36) had an ORR of 52.8%, including sCR, CR, VGPR, and PR rates of 2.8%, 16.7%, 27.8%, and 5.6%, respectively.

Overall, these findings support the use of elranatamab monotherapy as a treatment option for patients with RRMM after receiving BCMA-directed therapy.

“It is a new era that we are seeing, showing that you could retreat patients with BCMA-targeted treatments. This opens up a new field for us,” Ajay K. Nooka, MD, MPH, FACP, told Targeted Oncology^TM, in an interview.

In the interview, Nooka, professor and director of the Myeloma Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine, scientific director of Winship Data and Technology Applications Shared Resource at Winship Cancer Institute of Emory University in Atlanta, Georgia, discussed data from a pooled analysis of studies from the MagnetisMM program evaluating erlanatamab in RRMM.

Targeted Oncology: Can you discuss the mechanism of action of elranatamab and the rationale for studying the agent?

Nooka: Elranatamab is a BCMA-directed bispecific antibody. It targets the BCMA and the plasma cell and the CD3 on the T cells to enhance the T-cell mediated killing. What we've known was among the BCMA-naive patients, there is activity BCMA-targeting bispecific antibodies. What we do not know is what happens to these patients after they've previously been exposed to a BCMA-targeted treatment. So is it a BCMA ADC, which is an antibody drug conjugate that we have, belantamab [Blenrep], or a BCMA targeted CAR T. We have 2 of them approved, 1 of them is ide-cel and the second is cilta-cel.

What the study looked at was a post hoc analysis, a pooled analysis among 4 different studies that have enrolled patients who have previously received a BCMA-directed therapy, either an ADC or CAR T. There are a total of 87 patients that were enrolled on the trial [and] qualified.

Please explain the methods and design of the trial.

The study design is a pooled analysis. These are patients that have already been enrolled in the trial. When you look at the methodology, you're asking a few questions. The first 1 is, what is the efficacy as a primary end point? The other end points that we checked for were, is the safety profile consistent with the safety profile that we see with the BCMA patients in terms of the immune effector cell-associated neurotoxicity syndrome [ICANS], in terms of the cytokine release syndrome [CRS], in terms of the infection profile? And what is the PFS and the duration of response that you see with regiment like this as well as the CR rates?

Can you explain the efficacy findings?

It was surprising for us to see that even among these patients who have received a prior BCMA-directed therapy as ADC, or as a CAR T, you're still able to see the response rates in the range of 50%. To be precise, it's 46%. It is 52% for those patients that received a prior BCMA-directed CAR T, and 46% for those patients that receive a prior ADC. If you translate that into the duration of responses, these durations of response are durable, which means the patients who have a response continue to maintain that response for a long time. At that time, a median follow-up of 11.3 months, that was not achieved for those patients with CAR T. The time is around 17.1 months for those patients that received a prior ADC. If they get a response, they maintain that response for a long time.

Translating this to the overall survival advantage, we're talking about a new set of patient populations here, what we call penta refractory. These patients have received prior BCMA treatment as well. These 40% of patients qualify for what is called a hexarefractory status. For those patients and what the outcomes are that we have existing out there is undefined. This is a new group of patients and yet we are able to see an overall survival advantage of 1 year for these patients.

What were the safety findings?

The safety findings were exactly mimicking what we saw among the BCMA patients. Starting with overall safety, if you look at the hematological toxicities, those are almost mimicking the MagnetisMM study with MagnetisMM-3 basically enrolling patients who are naive to BCMA-targeted therapies. If you look at the toxicity profile, which is non hematological, the major toxicities are infections and CRS. Breaking down by CRS, the majority of these CRS events are grade 1 or grade 2. There was only 1 event of grade 3 among these 87 patients, and this all happened with 2 step-up dosings. The incidence decreased drastically from separate dosing 1 to step-up dosing to the full target dose and beyond the target dose or beyond the second full dose. There were only 2 patients that had low-grade CRS. The CRS profile is encouraging for us to look at. Looking at the infection profile, infections happened in around 73% of the patients, so this is 1 of the most common adverse events. But if you look at it and break it by the grade 3 and beyond toxicities, they were seen in close to 35% of the patients, which is consistent with what we see among the BCMA-naive patients.

Moving forward, how do you anticipate BCMA-targeted therapies continue to play a role in RRMM?

It is a new era that we are seeing, showing that you could retreat patients with BCMA-targeted treatments. This opens up a new field for us. Not only do we have alternate targets of GPRC5D or FCRH5 those patients that have previously received a BCMA-targeted therapy, but this study clearly shows that BCMA-targeted therapies could be reused yet attaining a good benefit for these patients.

REFERENCE:

1. Nooka AK, Lesokhin AM, Mohty M, et al. Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) and prior B-cell maturation antigen (BCMA)-directed therapies: A pooled analysis from MagnetisMM studies. J Clin Oncol. 2023;41(suppl 16):8008. doi:10.1200/JCO.2023.41.16_suppl.8008