Optimizing Bispecific Antibodies in Multiple Myeloma for Efficacy, Safety

Bispecific antibodies are revolutionizing the treatment of relapsed or refractory multiple myeloma, with ongoing research to improve their use in earlier treatment stages and manage potential side effects. However, their integration into oncology care requires key considerations for facility readiness and patient selection.

Bone marrow aspirate findings of patient with multiple myeloma / David A Litman - stock.adobe.com

At the Hematology/Oncology Pharmacy Association Annual Conference 2024 in Tampa, Florida, Drug Topics interviewed Kirollos Hanna, PharmD, on his presentation titled “Key Considerations for Operationalizing Bispecifics in Relapsed or Refractory Multiple Myeloma” to talk about considerations pharmacists should be aware of when optimizing bispecifics at their sites of care.

Drug Topics: Following the success of teclistamab-cqyv, are there any ongoing clinical trials investigating the efficacy of similar bispecific antibodies in earlier lines of treatment for multiple myeloma?

Kirollos Hanna, PharmD: When you look at the success of teclistamab-cqyv in multiple myeloma, one important thing to highlight is that we really haven't seen patients with myeloma achieve the degree of response, such as with teclistamab-cqyv, since daratumumab was first incorporated into the myeloma armamentarium. When daratumumab was first approved in 2015, 2016, we saw 40-plus percent overall response rates with daratumumab, and that was something groundbreaking, right? You didn't really have [many] novel options in myeloma since daratumumab. You had CD38 [cluster of differentiation 38] and you had elotuzumab SLAMF7 [signaling lymphocytic activation molecule F7] mechanism, but the CD38 mechanism has really blown up. [If] you're looking at daratumumab today, we're using daratumumab in frontline patient populations—transplant eligible and transplant ineligible—because it has made a significant dent in the outcomes for this disease.

The exact same trend is likely expected with the bispecifics in myeloma: teclistamab-cqyv, even [talquetamab], as well as elranatamab. These therapeutics have demonstrated very, very good efficacy profiles. Your degree of CRs [complete responses], your VGPRs [very good partial responses], and above, are very, very impressive. So, that’s the normal trajectory of drugs in myeloma; a drug gets approved [and is used in] a penta-refractory population, it gets combined with something else—and you even see better degrees of responses, more durable responses—and then we slowly start to transition these therapeutics into earlier lines of the disease because of the benefit.

READ MORE: Myeloma Expert: Earlier Use of Bispecifics Can Improve Patient Outcomes

One thing we know about myeloma is that patient attrition from line to line to line of therapy, we lose more patients. [If] you're looking at your patient attrition with your first relapse versus your patient attrition with your third or fourth relapse, you're seeing maybe 15% to 20% of patients go on to a third- or fourth-line [therapy] at that point, versus maybe 60% or 70% go on to a second-line therapy. That's just because this is an incurable disease, the nature of the disease transforms, and then these patients are only getting older—comorbidities, side effects from therapy [sometimes] does lead to treatment abandonment.

When you look at the ongoing clinical trials of things like teclistamab-cqyv and talquetamab and elranatamab, they're looking at unique strategies of, could you combine this BCMA [B-cell maturation antigen] and GPRC5D [G protein-coupled receptor, class C, group 5, member D] mechanism to induce even a better response? Could you switch the dose modification strategies? On top of all of that, there are numerous other targets being evaluated within myeloma and in many other hematologic cancers as well as solid tumor. The bispecifics are very, very exciting and I think, within myeloma, I'm expecting that we're likely going to be seeing these in earlier lines of therapy.

Drug Topics: While teclistamab-cqyv and blinatumomab have received FDA approval, how do their safety profiles differ, and how might this influence considerations for facility readiness and patient selection?

Hanna: When you look at some of the bispecifics, [therapies] like teclistamab-cqyv or blinatumomab or tebentafusp, as I mentioned, they tend to share very similar side effects of interest in terms of a safety profile. However, we do see some degree of variation—the incidence or the severity, like a grade 3 and 4 [adverse event; AE] may not be as prevalent with 1 [therapy] over the other. So, you'll look at something like teclistamab-cqyv; it has a REMs [Risk Evaluation and Mitigation Strategies] program. You'll look at something like tebentafusp; it doesn't have a REMs program. And ultimately, that's the FDA decision based on what they decide to do. However, CRS [cytokine release syndrome], ICANS [immune effector cell-associated neurotoxicity syndrome], neurotoxicities, [and] infections are shared side effects across the board. These are things that we have to be prepared to manage [in] our patients whether or not there's a REMs aspect. Now the REMS aspect will add some logistics to your overall operation, whether it's staff training, site readiness. documentation in the [electronic medical record]. But again, these AEs do tend to be shared across the board.

Now, operationally, I think there are some variabilities between these drugs, and health systems have to keep that in mind. Something like blinatumomab—it's a continuous infusion—you have to swap out bags [or] you might have to incorporate home infusion as part of blinatumomab administration. That’s something that's very different than a teclistamab-cqyv. Teclistamab-cqyv is a subcutaneous injection. You receive the injection over a few minutes, and we will see you a week or 2 weeks later. I think those operational considerations kind of provide some variability.

But I think overall, the key AEs tend to be very shared between them. Now, it doesn't mean that you won't find a bispecific therapy that doesn't have its nuanced adverse event. For example, you look at talquetamab; being that it targets GPRC5D, that is also expressed in your mouth, so in tastebuds, and it's also expressed in the [gastrointestinal] tract. When you look at something like talquetamab, patients in the clinical study experienced aphasia, they experienced taste changes, some of them completely lost their ability to taste while on treatment. And then you also [look at] patients within the study who had severe weight loss. And the data doesn't show us that taste changes were directly correlated to weight loss. So, you can have someone with taste changes that doesn't experience weight loss, and vice versa. They can lose weight, but it has nothing to do with their tastes. You’ll find some unique things but again, a lot of shared AEs that we can prep for and then operationally administration wise, you'll find some variability there between them.

READ MORE: Oncology Resource Center