Clinic Conversation of the Week: How to Talk to Patients About Talquetamab and Teclistimab for Multiple Myeloma

Waqas Haque, MD, MPH: Welcome to this Clinic Conversation of the Week, where we discuss groundbreaking research with our patients in the clinic. Today, I’ll be discussing a recently published clinical trial in the New England Journal of Medicine that looked at two drugs, teclistimab and talquetamab, for relapsed/refractory multiple myeloma. The goal of this series is to discuss the data with patients as if they were our own in the clinic, as if we were talking with them and they were asking us about the data and what the research shows. In this episode, I’ll be talking about the potential of this novel dual-targeting approach for multiple myeloma.

Here’s What I Would Say

“Multiple myeloma is a form of cancer that has really challenged oncologists for decades, especially in the relapsed or refractory form when it comes back even stronger than before. I’d like to discuss the promising results of a phase 1/2 trial—which means an early-phase clinical trial—that combined two groundbreaking bispecific antibodies called talquetamab and teclistimab. This combination represents a really novel approach for treating myeloma, especially for patients who have exhausted traditional treatment options, including proteasome inhibitors like bortezomib, immunomodulators like lenalidomide, or also anti-CD38 antibody treatments like daratumumab.

The clinical trial actually used a dual-targeting approach with the two drugs that I mentioned, talquetamab and teclistimab. Teclistimab targets a B-cell maturation antigen, or BCMA, which is a receptor, and it’s actually the only bispecific drug that’s approved that targets BCMA. It had a 60% response rate in a previous trial called MAJESTEC-1. The other drug that I mentioned, talquetamab, targets something with a little bit of a longer name, G protein-coupled receptor family C group 5 member D (GPRC5D). It had a 70% response rate in the MonumenTAL-1 trial.

Both antibodies are basically redirecting your immune cells or T cells through something called CD3 engagement, helping to create a two-pronged attack against myeloma cells. This dual antigen treatment is thought to enhance the potency of the treatment and also to help prevent resistance—preventing the cancer cell from becoming really smart and then having an even stronger form of cancer.

The study investigating the combination enrolled 94 patients who had relapsed or refractory myeloma, and 44 of the patients in this trial received the recommended phase 2 regimen of talquetamab at 0.8 mg/kg and teclistimab at 3 mg/kg every other week. The results were pretty impressive. What we saw were that there was an 80% response rate in patients who had the recommended dosing, and we actually saw 92% at the recommended phase 2 regimen among patients we could evaluate for disease.

The other nice thing about the results is that for patients who had myeloma outside the bone marrow and in their blood, which we call extramedullary disease, there was an 83% response rate. Even in this very aggressive form of myeloma, we saw patients with really good responses, and over half of patients had a complete response, meaning that when they did scans and imaging, they weren’t able to find any evidence of disease. There was a 33% complete for patients who had that more aggressive extramedullary disease that I talked about before. Another really nice thing is that for patients who did have a response, the chance of maintaining that response at 18 months was 86% with the recommended regimen.

When thinking about these bispecifics in the clinic, it’s really important to balance the safety of these drugs with the efficacy as well. The most common adverse side effects that we see with bispecifics are similar to other kinds of therapies called chimeric antigen receptor (CAR) T, which you might’ve heard of before. This includes cytokine release syndrome (CRS), which is an inflammatory reaction that feels like a viral infection. This can mean things like fever at its best, and at its worst, can lead to drops in blood pressure requiring oxygen and making people feel really sick. We saw really high grades of CRS in many of these patients and over half of them had some form of infection as well. These were severe for some patients. There was a small number of deaths in the study, which were generally from infection.

The one caveat that I will mention is that in myeloma, you can have patients who have low immune cells or low antibodies, so there are different ways for targeting that. But only half the patients got intravenous immune globulin (IVIG), which is a form of antibody treatment to help prevent infection. So, there are some caveats to some of the severe side effects that I mentioned earlier. There are some other side effects that these bispecifics have. Talquetamab can lead to things like some dry mouth and skin changes, which can lead to weight loss. Teclistimab can also cause infections and some motor and sensory deficits—some forms of neuropathy.

When thinking about practically implementing these therapies, it’s important to keep in mind that with all the risks of side effects, careful monitoring is important, especially when patients start this treatment. Most patients on the trial had to have some kind of treatment modification, whether that was delaying treatment for a period of time, or whether it was reducing the dose. That makes it even more important to have vigilant management, to have close patient follow up, and to ensure good caregiver support.

While the results of this study are very promising, there are several questions that remain. We need to better understand how this combination fits into the overall landscape of myeloma therapy, especially in relation to CAR T-cell therapy and other emerging treatments. We also need to investigate the role of looking at different bridging treatments while you wait to get CAR T, for people who are eligible for that. Also, I think the high infection rate warrants more investigation into how we can do other kinds of prophylactic strategies to help prevent infections in this patient group.

So, after decades of having very limited options for treating myeloma, especially for those who are very heavily pretreated and have cancer cells that have seen all sorts of drugs and are highly resistant, this combination approach is really a huge advance in the field. It’s an off-the-shelf availability drug, which means that it can be manufactured, unlike CAR T, which has to get processed specifically for the patient. I think in addition to being off-the-shelf, the fact that it has a really good durability makes it an important addition to our therapeutic arsenal for myeloma doctors, but we have to be careful about the side effects and patient management and follow-up. Thanks for listening.”

About Dr. Haque

Waqas Haque, MD, MPH, is a Hematology/Oncology Fellow at the University of Chicago. He recently completed his Internal Medicine Residency at New York University (NYU) in a Clinical Investigator Track. Dr. Haque has balanced his patient care work with a variety of research projects. During his fellowship training at the University of Chicago, he plans to further his work in innovative clinical trial design, value-based care delivery to cancer patients, and clinical investigation.