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Risk of Relapse: Predictions Among Patients With Ultra–High-Risk Multiple Myeloma

By: Celeste L. Dixon
Posted: Tuesday, March 5, 2024

Among patients with ultra–high-risk, newly diagnosed multiple myeloma, those more likely than others to relapse early after intensified treatment included patients with three or more high-risk cytogenetic abnormalities, an SKY92 high-risk signature, or del (17p) combined with an SKY92 high-risk signature, according to research results of an exploratory analysis presented during the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 881). Taking baseline clinical, laboratory, and tumor molecular characteristic factors into account may help with early identification of patients who would be potential candidates for “novel, innovative first-line therapeutic approaches,” noted Martin F. Kaiser, MD, FRCP, FRCPath, of the Royal Marsden Hospital NHS Foundation Trust, London, and colleagues.

Followed for a median of 51.5 months, patients received up to six cycles of daratumumab, bortezomib, lenalidomide, cyclophosphamide, and dexamethasone induction; bortezomib-augmented autologous stem cell transplantation; six cycles of daratumumab, bortezomib, lenalidomide, and dexamethasone (consolidation 1); and 12 cycles of daratumumab, bortezomib, and lenalidomide (consolidation 2). They then moved to monthly daratumumab and lenalidomide maintenance until disease progression. A total of 23 of the 107 patients (21%) experienced early relapse (defined by multiple myeloma relapse or multiple myeloma–related death within 18 months of registration) vs 84 patients (79%) who did not.

Here are some of the team’s findings:

  • Patient age and gender did not differ between the two groups.
  • Platelet levels as a continuous variable were lower in the early-relapse group (P = .0247).
  • International Staging System stage distribution differed between the groups (P = .0203). Most (56.5%) early-relapse participants had stage II disease vs 35.7% without early relapse.
  • Of 7 participants with three high-risk cytogenetic abnormalities, 5 experienced early relapse, vs 7 of 50 (14%) with two such abnormalities.
  • Of the 24 participants with an SKY92 standard-risk signature, 2 experienced early relapse, vs 20 of 82 patients with an SKY92 high-risk signature.
  • Of individual high-risk cytogenetic abnormalities, the presence of del (17p) alone was associated with early relapse (P = .002).

Disclosure: For full disclosures of the study authors, visit ash.confex.com.


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