Definition of Functional High-Risk Multiple Myeloma Updated in Era of Combo Therapy

TUESDAY, July 21, 2026 (HealthDay News) — In the era of combination quadruplet therapy (QUAD) + autologous stem cell transplantation (ASCT), functional high-risk (FHR) multiple myeloma (MM) should include patients who have disease progression within 36 months of therapy rather than 18 months, according to a study published online July 20 in Cancer.

Gayathri Ravi, M.D., from the University of Alabama at Birmingham School of Medicine, and colleagues analyzed 310 patients with newly diagnosed MM who received QUAD + ASCT with a median follow-up of 41.8 months to identify the optimal definition of FHR MM, historically defined as progression within 18 months of starting therapy. There were 66 progression events during follow-up.

The researchers found that the cumulative incidence of progression was 2.6, 6.2, 10.1, and 16.4 percent with FHR cutoff points of within 12 months (FHR12), 18 months (FHR18), 24 months (FHR24), and 36 months (FHR36) of treatment initiation, respectively. From the onset of second-line therapy, the median second progression-free survival (2PFS) and overall survival were 3.0 and 8.1 months, respectively, for FHR12; 2.7 and 8.1 months for FHR18; 3.3 and 15.7 months for FHR24; and 5.8 and 23.8 months for FHR36, indicating that 36 months was the optimal FHR definition. For patients treated with versus without T-cell-redirecting therapy, the 12-month 2PFS rate was 80 versus 23 percent. Even with adjustment for FHR status, T-cell-redirecting therapy was associated with considerably improved 2PFS.

“The findings will help physicians choose therapies for this important minority of patients who have disease progression in the first three years of diagnosis,” senior author Luciano J. Costa, M.D., Ph.D., also from the University of Alabama at Birmingham, said in a statement.

Several authors disclosed ties to the biopharmaceutical industry.

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