Patients With Functional High-Risk MM Could Benefit from Early Receipt of T-Cell Therapy

Key Takeaways:

• Functional high-risk (FHR) multiple myeloma (MM) should be defined as disease progression within 36 months of treatment initiation instead of 18 months.
• Patients with FHR MM who received T-cell therapy as second-line treatment had improved rates of survival than patients who did not receive T-cell therapy.
• Expanding the definition of FHR MM to progression within 36 months identified a larger population of patients with poor outcomes who may benefit from earlier risk-adapted treatment strategies.

FHR MM is commonly defined as disease progression within 18 months of beginning treatment. Patients with FHR MM tend to have poor outcomes and an overall survival (OS) of less than 2 years.

However, the emergence of quadruplet therapy (QUAD) combined with autologous stem cell transplantation (ASCT) has improved progression-free survival (PFS), but the outcomes and disease progression associated with this form of therapy remain unknown.

Study Methods and Outcomes

Researchers analyzed data from the MASTER trial and the University of Alabama database to determine the optimal definition of FHR MM and identify treatment patterns and responses.

The study included 310 patients with FHR MM who received QUAD plus ASCT. Researchers assessed the incidence of disease progression using the following FHR cutoff points: within 12 months (FHR12), 18 months (FHR18), 24 months (FHR24), and 36 months (FHR36) of therapy initiation.

The researchers also observed the PFS and OS of second-line therapy among these cohorts, noting the difference between patients who were treated with T-cell therapy and those who were not.

Incidences of Disease Progression and Impact of T-Cell Therapy

Out of the 310 participants, 66 experienced disease progression. The rates of progression among the different cohorts were as follows: 2.6% for FHR12, 6.2% for FHR18, 10.1% for FHR24, and 16.4% for FHR36.

Among the 66 patients who had disease progression, 11 received T-cell therapy, either with autologous chimeric antigen receptor (CAR) T-cell therapy or a bispecific T-cell engager.

The median second PFS (2PFS) was 3 months for FHR12, 2.7 months for FHR18, 3.3 months for FHR24, and 5.8 months for FHR36. Rates of 1-year 2PFS were 80% among patients who received T-cell therapy and 23% for patients without T-cell therapy.

The median OS of second-line therapy was 8.1 months for both FHR12 and FHR18, 15.7 months for FHR24, and 23.8 months for FHR36. Rates of OS at 12 months were 90% among patients who received T-cell therapy and 73% for patients without T-cell therapy.

The overall response rate (ORR) was 55% for progression at any time and 44% for patients in the FHR36 cohort. Patients who received T-cell therapy had an ORR of 91% as opposed to the 47% for patients who did not receive T-cell therapy.

Implications for Managed Care

The study’s findings illustrate FH36 as the new optimal definition of FHR MM as it represents a larger population of patients susceptible to poor survival outcomes with traditional therapy.

T-cell therapy shows promise in delaying disease progression and improving survival for patients with FHR MM, suggesting that these patients should be early recipients of this treatment.

According to the researchers, “[F]uture efforts should focus on better risk-predictive models for NDMM that would support the optimization of therapy and a further reduction in the proportion of patients with FHR multiple myeloma.”

Reference

Ravi G, Dhakal B, Callander NS, et al. Redefining functional high-risk multiple myeloma in the context of upfront quadruplet therapy and autologous stem cell transplantation. Cancer. 2026;132(14):e70478. doi:10.1002/cncr.70478