In a study reported in the Journal of Clinical Oncology, Bruinink et al constructed a transcriptomic classifier for primary plasma cell leukemia (PCL) that identified high-risk PCL-like disease in patients with newly diagnosed multiple myeloma.
As stated by the investigators, “Primary PCL is an aggressive subtype of multiple myeloma, which is distinguished from newly diagnosed multiple myeloma on the basis of the presence of ≥ 20% circulating tumor cells (CTCs). A molecular marker for primary PCL is currently lacking, which could help identify [newly diagnosed] patients with [multiple myeloma and] high-risk PCL-like disease, despite not having been recognized as such clinically.”
Study Details
In the study, a transcriptomic classifier for PCL-like disease was bioinformatically constructed and validated by employing data on baseline CTC levels, tumor burden, and tumor transcriptomics from 154 patients with newly diagnosed multiple myeloma included in two trials and 29 patients with primary PCL from one trial. Prognostic value of the classifier was tested in an independent cohort of 2,139 patients with newly diagnosed multiple myeloma from six studies.
Key Findings
High CTC levels were associated with the expression of 1,700 genes independent of tumor burden. From among these, 54 genes were selected to construct the transcriptomic classifier representing PCL-like disease.
The classifier had 93% sensitivity in identifying primary PCL. Among 2,139 patients with newly diagnosed multiple myeloma in the validation cohort, 214 (10%) were identified by the classifier as having PCL-like multiple myeloma.
PCL-like multiple myeloma resembled primary PCL transcriptionally and cytogenetically but was associated with significantly lower CTC levels (median = 3.0% vs 35%, P < .0001) and lower tumor burden (median = 36% vs 71%, P = .045).
In multivariate analysis among patients with newly diagnosed multiple myeloma in the validation cohort including Revised International Staging System stage, age, and treatment, PCL-like multiple myeloma was associated with significantly poorer progression-free survival (hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.30–2.07) and overall survival (HR = 1.89, 95% CI = 1.42–2.50).
The investigators concluded, “Primary PCL was identified on the basis of a specific tumor transcriptome, which was also present in patients with high-risk newly diagnosed multiple myeloma, despite not being clinically leukemic. Incorporating PCL-like status into current risk models in newly diagnosed multiple myeloma may improve prognostic accuracy.”
Davine Hofste op Bruinink, MD, MSc, of the Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the European Union’s Horizon 2020 research and innovation Program, Dutch Cancer Foundation, European Myeloma Network, and by Janssen and Celgene. For full disclosures of the study authors, visit ascopubs.org.
