The presence of 2 or more cytogenetic risk markers is associated with inferior outcomes after autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM), according to findings published in HemaSphere.

Researchers found that patients with 2 or more cytogenetic risk markers had significantly shorter progression-free survival (PFS) and overall survival (OS) than patients with 0-1 markers.

The researchers evaluated the association between outcomes and cytogenetic risk markers in 139 MM patients who received a combination induction regimen followed by ASCT. The risk markers included t(4;14), t(14;16), t(14;20), gain(1q), and del(17p).

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A total of 13 patients had at least 2 of the markers (double-hit MM), 55 patients had 1 marker (single-hit MM), and 71 patients had none of the markers (no-hit MM).  

At a median follow-up of 35.6 months, patients with double-hit MM had significantly shorter PFS and OS than patients with single-hit or no-hit MM. 

The median PFS was 15.1 months in the double-hit group, 24.6 months in the single-hit group, and 35.7 months in the no-hit group (P =.00063). The median OS was 49.2 months in the double-hit group and was not reached for the single-hit and no-hit groups (P =.034).

In a multivariate analysis, the following factors were associated with shorter PFS:

  • Double-hit MM (hazard ratio [HR], 4.27; 95% CI, 2.00-9.10; P <.001)
  • Single-hit MM (HR, 3.21; 95% CI, 1.80-5.73; P <.001)
  • International Staging System stage 3 (HR, 3.11; 95% CI, 1.56; P =.001)
  • A response to induction that was less than a very good partial response (HR, 0.38; 95% CI, 0.22-0.64; P <.001). 

The following factors were associated with shorter OS in a multivariate analysis:

  • Double-hit MM (HR, 4.01; 95% CI, 1.14-14.1; P =.03)
  • Single hit MM (HR, 3.47; 95% CI, 1.30-9.26; P =.013)
  • International Staging System stage 3 (HR, 4.66; 95% CI, 1.59-13.6; P =.005). 

“[O]ur results strongly support detailed genetic profiling at diagnosis for all patients planned to undergo ASCT in SoC [standard of care] and utilization of double-hit genetics for improved risk prediction and potential future risk-based treatment adaptation in the real-world setting,” the researchers concluded. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Panopoulou A, Easdale S, Ethell M, et al. Impact of ultra high-risk genetics on real-world outcomes of transplant-eligible multiple myeloma patients. HemaSphere. Published online January 25, 2023. doi:10.1097/HS9.0000000000000831

This article originally appeared on Cancer Therapy Advisor