Elranatamab Shows Activity, Safety as Compassionate Use in R/R Multiple Myeloma

Mohamad Mohty, MD, PhD

Findings from a retrospective analysis demonstrated that elranatamab-bcmm (Elrexfio) was active and safe in patients with relapsed/refractory multiple myeloma who were treated as part of the French compassionate use program.

Real-world data presented at the 2024 EHA Congress revealed at a median follow-up of 15.5 months (range, 3.4-18.8), a heavily pretreated population of patients with relapsed/refractory multiple myeloma administered elranatamab (n = 101) achieved an overall response rate (ORR) of 51.5%, including a very good partial response (VGPR) or better rate of 42%. Notably, 22% of patients experienced a VGPR or better after 1 cycle of treatment.

Additional data showed the median duration of response (DOR) was 11 months (95% CI, 8–not applicable), and 1-year DOR rate was 48% (95% CI, 31.1%-64%). The median overall survival (OS) was 10.1 months (95% CI, 6.79-13), and the 1-year OS rate was 41.9% (95% CI, 31.7%-52.1%).

Regarding safety, the rates of grade 1 and 2 cytokine release syndrome (CRS) were 35% and 10%, respectively, and no instances of grade 3 or higher CRS were reported. Grade 1, grade 2, and grade 5 immune effector cell–associated neurotoxicity syndrome occurred in 1 patient (1%) each. The rates of any-grade infections and serious grade 3 or higher infections were 49% and 24%, respectively.

“This compassionate use program proved to be extremely useful to patients who were in need and who otherwise wouldn't have had any other treatment option,” Mohamad Mohty, MD, PhD, said in an interview with OncLive®.

In the interview, Mohty expanded on the goal of the French compassionate use program, how data were gathered for patients treated in the program, and the efficacy and safety findings for elranatamab in this patient population.

Mohty is a professor of hematology and head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, and leader of the translational research team at Saint-Antoine Research Center in Paris, France. He is also chairman of the Acute Leukemia Working Party and past president of the European Society for Blood and Marrow Transplantation.

OncLive: What was the rationale behind evaluating elranatamab in this real-world population of patients with relapsed/refractory multiple myeloma? What key differences are worth noting between this compassionate use population and a clinical trial population?

Mohty: We have seen some incredible advances in the [treatment] of [patients with] relapsed/refractory multiple myeloma, especially those patients who are triple class–exposed or triple class–refractory. These are the patients who [previously] received an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug. At the time of relapse, these are patients who I would consider hard to treat. This is why immune therapies are bringing much hope for this population. Immune therapies can [include] either CAR T-cell therapies or bispecific antibodies.

The choice of the target [for immune therapies] is a crucial parameter. BCMA has proved to be an attractive target, and this is why [the CAR T-cell therapies] idecabtagene vicleucel [ide-cel; Abecma] and ciltacabtagene autoleucel [cilta-cel; Carvykti] are directed against BCMA. Both [CAR T-cell therapies] are approved and used [in practice].

However, we also have bispecific antibodies approved [that are] directed against BCMA: teclistamab-cqyv [Tecvayli] and elranatamab. Both of these agents were approved based on [data from] single-arm, phase 2 clinical trials, which could establish the efficacy, feasibility, and safety profile of these agents.

After getting data from a clinical trial and approval, it's also important to get information about patients who are treated outside of a clinical trial, especially, for instance, those patients who are treated as part of a compassionate use program. We know these are the patients who received the drug very early, and that these are the most difficult patients [to treat]. This is what we aimed to do as part of the analysis of the compassionate use program of elranatamab in France.

How did you collect and analyze data from patients treated with elranatamab through the French compassionate use program?

We asked centers that used the drug in patients [who were part of the compassionate use program] to report on the [patient] characteristics and features of the disease. We asked them to report on responses, as well as the safety profile and complications.

In a short period of time, we gathered a cohort of 101 patients who received [elranatamab] in the compassionate use program. When we went a little bit deeper into the characteristics of these patients, we found that they had highly advanced [disease], were fragile, and were heavily pretreated patients. Nearly 35% of patients had an ECOG performance status of 2 or higher. You would imagine how frail these patients were, and most of them were in a situation of supportive care. They didn't have any other [treatment] options. Suddenly, this compassionate use program emerged, and physicians applied to get access to the drug [for these patients].

These were patients who received a median of 5 prior lines of treatment [range, 1-17; interquartile range, 3-6]. They had received all the available agents at the time of the compassionate use program in France. Additionally, 34.5% of patients had extramedullary disease, and we know extramedullary disease [is associated with poorer] outcomes. A significant proportion of these patients [16.8%] received prior anti-BCMA therapy, particularly CAR T-cell therapies. Eight percent also had severe kidney dysfunction [with a creatinine clearance below 30 mL/min].

If you [consider] all of these characteristics, these [patients] were quite different from the patients who were included in the [phase 2 MagnetisMM-3] trial [NCT04649359]. [The majority of the patients in the compassionate use program] wouldn't have been included in the clinical trial.

It is important to figure out the efficacy and safety profile of elranatamab in a difficult-to-treat patient population whose [baseline] characteristics are worse than those patients included in the registrational MagnetisMM-3 trial.

What were the key efficacy data presented at the 2024 EHA Congress?

When it comes to efficacy in this compassionate use program—despite having the [most difficult-to-treat] group of patients in terms of disease characteristics and features—we were pleased and impressed to observe an ORR of 51.5%. This is in line with what we know about the efficacy of elranatamab. The other important piece of information is that the VGPR or better [rate was 42%]. This is very important because obviously a good response—whether it be a complete remission or a VGPR—is going to correlate with an improved outcome.

When it comes to progression-free survival, unfortunately, it's difficult to draw conclusions, because these were not patients who were treated in a clinical trial. There was no prespecified assessment for the time for progression. What we could capture in a more accurate fashion was the DOR, and the median DOR was 11 months, which is quite amazing for this [patient] population. The overall efficacy of elranatamab, even in the hard-to-treat patients, in my opinion, is well established.

What was reported in terms of safety?

The other important piece of information is about safety. For me, this is the key message of this study. Despite the [poor] general status of these patients, we saw a rate of infectious complications that was significantly lower to what was observed in [MagnetisMM-3]. This can be explained by the fact that at time of the compassionate use program, we had generated an important campaign of awareness around the management of infectious complications [for patients being treated with elranatamab]. This is a reason why 50% of patients included in the compassionate use program received supplementation with immunoglobulin, and that helped to reduce the rate of infections. There were strong recommendations on monitoring and screening of infectious complications.

We ended up with a severe infection [grade 3 or higher] rate of 24% compared with the rates of approximately 50% to 60% seen in other registrational trials for bispecific antibodies.

Putting the safety and efficacy data [together], we have robust information about elranatamab, even in a difficult-to-treat patient population. I would like to emphasize the feasibility of using bispecific antibodies in patients with kidney failure, even in those who receiving dialysis. We've published case reports about patients receiving bispecific antibodies, whether teclistamab or elranatamab, who receive dialysis.

Reference

Malard F, Bobin A, Labopin M, et al. Efficacy and safety of elranatamab monotherapy in the real-world setting in relapsed-refractory multiple myeloma (RRMM): results of the French compassionate use program on behalf of the IFM. Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract P906.