Optimizing Treatment in Myeloma With Biweekly Dosing of Talquetamab

Cesar Rodriguez, MD

Talquetamab (Talvey), a bispecific T cell engager, offers a promising treatment option for relapsed/refractory multiple myeloma. According to Cesar Rodriguez, MD, findings from a new study show that biweekly dosing with talquetamab is preferred in clinical practice over weekly dosing.¹

This schedule offers greater convenience for patients and may lead to better outcomes, including improved progression-free survival and duration of response. For safety, cytokine release syndrome (CRS) is the most common adverse effect, typically grade 1, and manageable with tocilizumab.

“Talquetamab provides an effective option for patients refractory to multiple myeloma therapies, without compromising the potential efficacy of chimeric antigen receptor [CAR] T therapy in the future,” Cesar Rodriguez, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai and the clinical director for the myeloma program, center of excellence at Mount Sinai Hospital, told Targeted Oncology^TM, in an interview.

In the interview, Rodriguez discussed several key aspects of this study and the use of talquetamab in the treatment of relapsed/refractory multiple myeloma.

Multiple myeloma cells: © David A Litman - stock.adobe.com

Targeted Oncology: Would you mind giving some background on the mechanism of action of talquetamab?

Rodriguez: Talquetamab is a bispecific T cell engager that uses the immune system to identify plasma cells, particularly myeloma cells, so that the immune system can destroy myeloma. It binds to a protein on the myeloma cell surface called GPRC5D, and also binds to a protein on the T cell surface called CD3. Once bound to both cells, it activates the T cell to attack and destroy the myeloma cell.

Can you discuss your study that looked at talquetamab in clinical settings?

We took advantage of talquetamab’s approval in the US in September 2023, collecting data from 11 physicians on commercial use and some clinical trials to evaluate how this drug is being implemented. We aimed to improve our management of potential [adverse] effects in patients.

What are the primary advantages of using talquetamab with a biweekly dosing schedule, and how does that compare with traditional dosing?

Talquetamab was approved based on the phase 1/2 clinical trial called MonumenTAL-1, which evaluated two dosing schedules. One used 0.4 mg/kg weekly after two step-up doses, and the other used 0.8 mg/kg biweekly after three step-up doses. Most physicians are using biweekly dosing. Both dosing schedules are effective, but biweekly dosing is more practical for patients as it reduces visit frequency, and it may reduce [adverse] effects. Updated data also suggests that biweekly dosing might offer better outcomes regarding progression-free survival and response duration.

How did you decide between inpatient, outpatient, or hybrid settings for step-up dosing with talquetamab?

Resource availability determines whether an institution administers therapy outpatient, hybrid, or inpatient. Institutions already performing outpatient stem cell transplants can more easily adopt outpatient or hybrid dosing. Facilities with outpatient or hybrid models often have systems in place for monitoring, such as on-body devices, daily calls, or clinic visits to identify early signs of CRS, infection, or neurotoxicities and manage symptoms accordingly.

Can you discuss some of the safety findings and the most effective strategies for managing GPRC5D-related oral symptoms in patients on talquetamab?

The most common adverse effect is cytokine release syndrome [CRS]. Most patients developed grade 1 CRS, about 28% developed grade 2, and one patient developed grade 3 CRS. In practice, most patients have grade 1 CRS, which we manage with tocilizumab and/or dexamethasone. Using tocilizumab decreases the likelihood of recurrent CRS episodes, so we encourage its use. Neurotoxicity was rare, and any neurologic symptoms were managed with dexamethasone or anakinra, resolving within a day or 2 without lasting effects.

Other [adverse] effects include dysgeusia, nail changes, and skin rashes. Dysgeusia often occurs early, even with step-up doses, affecting many patients. We use dexamethasone and nystatin mouth rinses from the start of step-up doses to prevent it, with rinses done three times daily. Another preventive approach involves icing with popsicles or ice packs on the cheeks to reduce blood flow and drug circulation to the salivary glands and tongue. These strategies seem to help, though we’re still evaluating their effectiveness.

What key findings or takeaways from the study would you like community or academic oncologists to know?

Key takeaways include using biweekly dosing initially and spacing treatment to monthly once achieving the desired response to reduce [adverse] effects without affecting efficacy. Another point is that talquetamab's [adverse] effects are manageable, and the benefits for patients outweigh the risks. Few patients discontinue therapy due to [adverse] effects. Finally, talquetamab provides an effective option for patients refractory to multiple myeloma therapies, without compromising the potential efficacy of CAR T therapy in the future.

What additional real-world data or insights would help refine talquetamab dosing and symptom management for relapsed, refractory multiple myeloma?

We would like to know if talquetamab’s efficacy is impacted if therapy is stopped after a set period—such as 1 or 2 years—if the patient achieves and maintains stringent remission. Although the study was designed for ongoing treatment until disease progression, in clinical practice, finite treatment periods are desirable. Data on outcomes with limited therapy duration would be valuable in establishing future care standards.

REFERENCE:

Schinke C, Dhakal B, Mazzoni S, et al. Real-world experience with clinical management of talquetamab in relapsed/refractory multiple myeloma: a qualitative study of US healthcare providers [published correction appears in Curr Med Res Opin. 2024 Oct;40(10):1827-1828. doi: 10.1080/03007995.2024.2401192]. Curr Med Res Opin. 2024;40(10):1705-1711. doi:10.1080/03007995.2024.2387183