Hi, my name is Attaya Suvannasankha.
I am a myeloma physician at Indiana University School of Medicine and Simon Cancer Center.
I also practice at our Annapolis VA Medical Center.
I'm excited to share initial safety and efficacy results from a clinical trial called MagnetisMM-30.
The clinical trial is exploring two different classes of drugs, but using them together in patients with relapsed refractory multiple myeloma.
One drug is called elranatamab. It's already been approved as a single agent in patients who have failed at least four prior lines of therapy, including immunomodulatory agents, proteasome inhibitors, and the CD38 antibody.
While there is an important message in that, we would like to understand how to use them by boosting efficacy, but also be able to use them a little bit earlier in the patient's journey.
The drug works by grabbing onto the T cells and actually pulling them together to attack the cancer cell. That class of drug is called a bispecific antibody.
We're using it together with a pill called iberdomide. The drug is not yet approved, but it is a new class that is improving efficacy and also the ability to activate T cells compared to the immunomodulatory agents.
So in this case, it would appear that we're combining things that are helping each other out on how to kill a cancer, and we're exploring them together.
In the clinical trial, there are two parts. Part one is what we call dose escalation, which is really to understand the right dose and also the toxicity of the combination. Part two is going to expand to a larger number of patients.
I'm going to report the data from part one only. Patients would classically receive what we call step-up dosing of elranatamab. They start with a baby dose, then a middle dose, and then the residual dose. Once they complete that step-up dosing, they start on the combination.
The elranatamab is a standard dose: 76 mg subcutaneously once a week. The iberdomide capsule is one milligram, which is a dose commonly used across multiple clinical trials because there were some side effects occurring in the population.
We also have data from what we call a dose-minus-one, a slightly less intense dosing: elranatamab same dose, but given every other week rather than weekly, and the dose of oral iberdomide is the same.
The whole idea is to look at dose-limiting toxicity, meaning any adverse events or side effects, and also look at the overall response rate, complete remission, and so on.
So far, 22 patients have been enrolled. The first group had 13 patients, and the lower dose cohort had nine patients.
Although in theory patients could have had relapsed refractory myeloma and have held at least one line of therapy, it turned out that the group that went on were people who had failed more therapies than what’s required.
About half of the patients are triple-class refractory, meaning they’ve already progressed across all three different classes of drugs. About 86% of them progressed on the last therapy they received.
We also had patients with disease outside the bone marrow, called extramedullary disease. That's a group that is very difficult to treat. A single agent just didn't seem to achieve similar responses compared to patients without that aggressive disease.
We also included about 40% of people with high-risk cytogenetics—genetic changes that predict the cancer will be more aggressive.
The long and short of it is that the overall response rate is about 95.5%, which is quite impressive. We didn't see that kind of response with single-agent elranatamab.
Iberdomide has been combined with a variety of things, not yet approved, but across multiple studies. This 95.5% is also looking better compared to some of the iberdomide studies alone.
We mentioned two different doses. The standard and lower dose cohorts had the same response, with the second cohort actually showing 100% response. The response occurred pretty early, a little over a month into treatment, so you’ll know whether the therapy is working or not.
So far, about 45% of patients have achieved complete remission or better. With these drug classes, response tends to improve over time. Most patients have been on treatment for an average of 7.8 months, so some are still in the early part of treatment.
We are also encouraged by the side effects, which are similar to what we anticipated with either drug alone. Cytokine release syndrome—the fever, low blood pressure, oxygen changes—or the neurotoxicity seen with bispecific antibodies had similar percentages and severity to elranatamab alone.
The key side effect requiring dose reduction is a drop in neutrophils, a type of white blood cell. When neutrophils drop, patients have an increased risk of infection, and some receive growth factor support to boost their neutrophils.
Comparing the two cohorts, we were more successful at delivering the dose in the second cohort, which was easier for patients and maintained the same response rate. That’s very encouraging.
The study is still ongoing. We'll continue reporting updated side effects and responses in these patients, and more patients will be enrolled in part two to explore dose optimization. Now that we know what works, we aim to adjust it to make it easier while maintaining efficacy.
People often ask, “Do you need to choose one drug first? Is one better than the other? Can you save the other for later?”
We’ll also conduct correlative science studies to look at T-cell function in patients receiving both drugs. We already have data on their immune cells with one drug alone, and we hope to show whether the pill adds to elranatamab by boosting T-cell function.
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