Daratumumab may improve PFS for patients with myeloma and high-risk cytogenetics
Adding daratumumab to backbone regimens improved PFS for patients with multiple myeloma and high-risk cytogenetics, both in the first-line and relapsed or refractory setting, according to data presented at ASCO20 Virtual Scientific Program.
“Despite decades of improvement in survival of patients with multiple myeloma, outcomes among those with high-risk cytogenetics remain poor and clinical trials are rarely done in this specific subset of patients,” Smith Giri, MD, MHS, of the Institute for Cancer Outcomes and Survivorship at The University of Alabama at Birmingham, told Healio. “Given that only 15% to 20% of patients overall have high-risk cytogenetics at diagnosis, most all-comer trials tend to be underpowered for this subset. For these reasons, the best drugs and regimens for the management of this disease remains unclear.”
Giri and colleagues conducted a systematic search of bibliographic databases, clinical trials registries and meeting libraries for randomized phase 3 trials that compared backbone multiple myeloma regimens with same regimen plus daratumumab (Darzalex, Janssen) and reported outcomes by cytogenetic risk status (high risk vs. standard risk). PFS served as the primary endpoint.
The researchers pooled the relative efficacy results of daratumumab across six trials, including three trials in first-line setting (n = 2,528; high-risk cytogenetics, n = 358) and three in relapsed or refractory setting (n = 1,533; high-risk cytogenetics, n = 222).
Giri and colleagues found that incorporating daratumumab into backbone regimens for multiple myeloma among patients with high-risk cytogenetics led to improved PFS with little heterogeneity in the first-line setting (pooled HR = 0.67; 95% CI, 0.47-0.95) and in the relapsed or refractory setting (pooled HR = 0.45; 95% CI, 0.3-0.67; Cochran’s Q = 0.63, P < .01, I2 = 0).
They observed similar results among patients with multiple myeloma and standard-risk cytogenetics in the first-line setting (pooled HR = 0.45; 95% CI, 0.37-0.54; Cochran’s Q P = 0.49, I2= 0]) and relapsed or refractory setting (pooled HR = 0.38; 95% CI, 0.25-0.56; Cochran’s Q P = 0.04, I2 = 70%).
Giri told Healio that the association between daratumumab and improved PFS among patients with high-risk cytogenetics appeared uniform regardless of which backbone regimen was used.
“Although the impact of daratumumab among [patients with] high-risk cytogenetics is less pronounced than [for] those with standard-risk disease, this is generally true across all studied regimens in multiple myeloma. This result argues in favor of use of daratumumab for patients with high-risk cytogenetics,” Giri said. “However, our results are not definitive and need to be confirmed in larger studies, ideally randomized trials that are well powered to answer this question within the high-risk cytogenetic subset.”
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Giri S, et al. Abstract 8540. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.