In a retrospective study reported in the Journal of Clinical Oncology, Kaiser et al found that the presence of two or more high-risk cytogenetic abnormalities was associated with poorer outcomes in patients with newly diagnosed multiple myeloma (MM) and relapsed or refractory MM.
Study Details
The study involved data from randomized controlled trials in newly diagnosed MM and relapsed or refractory MM that reported testing for high-risk cytogenetic abnormalities between January 2000 and December 2021. Outcomes among patients with one high-risk cytogenetic abnormality and two or more high-risk cytogenetic abnormalities were analyzed.
Key Findings
A total of 24 trials including 13,926 patients were included in the analysis.
Compared with patients who had no high-risk cytogenetic abnormalities, progression-free survival was worse among those with one high-risk cytogenetic abnormality (hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 1.38–1.65) and among those with two or more high-risk cytogenetic abnormalities (HR = 2.28, 95% CI = 2.05–2.54). Similarly, overall survival was worse among patients with one high-risk cytogenetic abnormality (HR = 1.69, 95% CI = 1.52–1.88) and among those with two or more high-risk cytogenetic abnormalities (HR = 2.94, 95% CI = 2.49–3.47).
Among patients with two or more high-risk cytogenetic abnormalities, hazard ratios for progression-free survival were 2.53 (95% CI = 2.26–2.84) among those with transplant-eligible newly diagnosed MM, 1.97 (95% CI = 1.55–2.50) among those with transplant-ineligible newly diagnosed MM, and 2.05 (95% CI = 1.66–2.54) among those with relapsed or refractory MM. The respective hazard ratios for overall survival were 4.17 (95% CI = 3.34–5.22), 2.31 (95% CI = 1.92–2.78), and 2.21 (95% CI = 1.83–2.67).
In studies started since 2015, involving 2,312 patients, hazard ratios among all patients with two or more high-risk cytogenetic abnormalities were 2.39 (95% CI = 1.96–2.91) for progression-free survival and 3.10 (95% CI = 2.10–4.60) for overall survival. Hazard ratios among patients with newly diagnosed MM were 2.62 (95% CI = 2.05–3.35) for progression-free survival and 4.81 (95% CI = 2.85–8.13) for overall survival. Hazard ratios among patients with relapsed or refractory MM were 2.34 (95% CI = 1.66–3.30) for progression-free survival and 2.45 (95% CI = 1.61–3.73) for overall survival.
As stated by the investigators: “Heterogeneity related to transplant eligibility and relapsed/refractory status was as expected.”
The investigators concluded: “The association of [two or more] high-risk cytogenetic abnormalities with the poorest outcome in [newly diagnosed] MM and [relapsed/refractory] MM, and across treatment modalities, as demonstrated here for the first time to our knowledge, allows for more focused development of novel approaches to these patients with high unmet need.”
Martin F. Kaiser, MD, of the Royal Marsden Hospital NHS Foundation Trust, London, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Myeloma UK, Cancer Research UK, and others. For full disclosure of all study authors, visit the Journal of Clinical Oncology.
