Black Patients May Experience More Significant Side Effects
- The data from MonumenTAL-1 underscore talquetamab’s potential as a transformative therapy in relapsed or refractory multiple myeloma, offering encouraging response rates in a population with limited treatment options.
- Black patients in the study experienced favorable ORRs and PFS, but also experienced more significant side effects — particularly skin and taste toxicities.
- Oncologists and hematologists treating Black patients with talquetamab may need to anticipate a higher likelihood of certain toxicities, particularly skin and taste disturbances, and prepare supportive interventions preemptively.
As multiple myeloma therapies continue to evolve, bispecific antibodies have increasingly drawn attention due to their novel mechanisms and encouraging clinical outcomes in heavily pretreated patients. Talquetamab (brand name Talvey), a first-in-class GPRC5D×CD3 bispecific antibody, represents a new frontier for patients who have developed resistance to standard-of-care regimens.
Its mechanism—bridging T cells and multiple myeloma cells through the GPRC5D target—facilitates a highly specific immune response against malignant plasma cells. This approach has shown promise in relapsed/refractory multiple myeloma (RRMM), a particularly challenging population often with diminishing options.
Early-phase data from the MonumenTAL-1 study underpinned talquetamab’s approval, demonstrating robust overall response rates (ORRs) in heavily pretreated patients. Since talquetamab’s target antigen, GPRC5D, is ubiquitously expressed on myeloma cells but also on healthy tissues such as keratinocytes and taste buds, the drug’s safety profile has inevitably included on-target, off-tumor effects. These effects may manifest as skin-related toxicities and taste alterations (dysgeusia), aspects that require careful monitoring and management.
A noteworthy consideration in interpreting and applying these results clinically is the patient population that participated in pivotal studies. Early research indicates that Black patients may experience more significant side effects of talquetameb than white patients — an important caveat to consider when making a treatment plan.
Outcomes in Black Patients with Relapsed/Refractory Multiple Myeloma
Dr. Carolina Schinke, a hematologist/oncologist at the University of Arkansa, presented new data on the use of Talquetamab, at the 2024 American Society of Hematology Annual Meeting — and tells SurvivorNet Connect that there is research that indicates Black patients may fare worse when it comes to skin and taste toxicity.
“We looked retrospectively at our data. We looked at patients that were African-Americans and those were roughly 10% of the whole study population. We’re not dealing with a whole lot of patients, but it helps us to get a little bit of an idea,” Dr. Schinke says. “Looking at these 10% of Black Americans in the academic trials, what we could see is the overall response rate efficacy seemed to be very similar across all patients and across all races. But when we looked at skin toxicity and particularly taste toxicity we did see that there seemed to be more African-Americans affected by skin toxicity as well as dysgeusia compared to caucasians.”
What are the Clinical Outcomes?
The overall response rates (ORR) for Talquetamab in MonumenTAL-1 was impressive, particularly in the once-weekly dosing cohort among Black patients:
-In the QW cohort (talquetamab at 0.4 mg/kg subcutaneously once weekly), Black patients achieved an ORR of 100% (12/12), while white patients had an ORR of 71.9% (92/128).
-In the Q2W cohort (talquetamab at 0.8 mg/kg subcutaneously every other week), Black patients’ ORR was 52.9% (9/17), compared to 71.4% (90/126) in white patients.
This differential efficacy signal raises interesting questions. For the QW dosing schedule, Black patients appeared to fare exceptionally well, with every patient responding. The reason for this difference is not fully elucidated by the current data.
Durability of Response
Sustained remissions are critical in RRMM, as patients generally have limited treatment options. Here, 12-month duration of response (DOR) rates were considered:
-In the QW cohort, the 12-month DOR was 50.5% in Black patients and 42.9% in white patients.
-In the Q2W cohort, the 12-month DOR was 53.3% in Black patients and 62.9% in white patients.
These data suggest that when Black patients respond—particularly at the QW dose—their responses can be clinically durable. The slightly lower 12-month DOR in Q2W Black patients compared to white patients may again tie back to disease burden, extramedullary disease involvement, or dosing schedule intricacies. Given the small sample sizes, caution is warranted in drawing definitive conclusions.
Progression-Free Survival
Progression-free survival (PFS) is a critical metric in RRMM, reflecting both short-term efficacy and the potential for prolonged disease control:
-In the QW cohort, the 12-month PFS rate was 61.4% for Black patients and 32.7% for white patients.
-In the Q2W cohort, the 12-month PFS rate was 30.0% for Black patients and 49.9% for white patients.
These findings mirror the ORR and DOR patterns. At the QW dosing regimen, Black patients experienced a notably better 12-month PFS than white patients, while the opposite trend appeared in the Q2W cohort. Further studies are needed to disentangle whether these observations represent a reproducible difference driven by biological or pharmacological factors, or whether they reflect statistical noise in a small subgroup.
Safety Profile
“Talquetamab has been already approved, but what we are trying to elucidate a little bit more is if the side effect profile is different in African-American compared to Caucasian patients. And this is based on preliminary data and on anecdotal data that GPRC5D is not only expressed in myeloma cells but also in skin tissue as well as in taste buds in the mouth,” Dr. Schinke explains.
“One prominent side effect has been shown to be skin changes like rash and what we call dysgeusia, which is the change in taste. And since African-American patients tend to have thicker skin, there might be a, hypothetically, different side effect profile compared to Caucasian patients who tend to have thinner skin.”
“When we looked at skin toxicity and particularly taste toxicity (dysgeusia), we did see that there seemed to be more African-Americans affected by skin toxicity as well as dysgeusia compared to Caucasians,” she adds.
Dysgeusia (Taste-Related AEs) and Skin Toxicities
GPRC5D expression in non-hematopoietic tissues results in distinctive side effects, particularly taste alterations (dysgeusia) and skin-related AEs.
Dysgeusia
-QW: 83.3% in Black vs. 71.1% in white patients
-Q2W: 94.1% in Black vs. 69.0% in white patients
Skin-Related AEs
-QW: 91.7% in Black vs. 54.7% in white patients
-Q2W: 82.4% in Black vs. 73.8% in white patients
Black patients consistently experienced higher rates of dysgeusia and skin AEs across both dosing cohorts. While these toxicities were predominantly low grade (Grade 1/2), their higher incidence and potentially prolonged duration in Black patients may warrant a more proactive supportive care approach.
Notably, Black patients often received more concomitant medications (e.g., topical therapies, antihistamines, or steroids) to manage skin-related issues. Duration of these AEs also tended to be longer in Black patients—averaging around 50-63 days versus 29-39 days in white patients. Although such events did not frequently lead to discontinuation, their effect on patient quality of life and adherence should not be underestimated.
Given the significance of these findings, clinicians may consider implementing earlier and more aggressive prophylactic and symptomatic interventions for skin and taste-related toxicities, particularly in Black patients. This might include preemptive counseling on dietary modifications, topical treatments, and closer follow-up to ensure that these discomforts do not become treatment-limiting.
What’s Next?
The data from MonumenTAL-1 underscore talquetamab’s potential as a transformative therapy in RRMM, offering encouraging response rates in a population with limited treatment options. However, the emerging signals of differential safety and efficacy profiles in Black patients demand further investigation. Understanding why Black patients in the QW cohort experienced particularly favorable ORRs and PFS—and why they also had a higher incidence of certain toxicities—will require additional studies with larger sample sizes and prospective designs focused on racial and ethnic subgroups.
From a clinical standpoint, these preliminary findings highlight the importance of individualized management plans. Oncologists and hematologists treating Black patients with talquetamab may need to anticipate a higher likelihood of certain toxicities, particularly skin and taste disturbances, and prepare supportive interventions preemptively. Similarly, identifying the optimal dosing schedule could be important in maximizing efficacy while minimizing toxicity and avoiding unnecessary dose modifications.