Archival Blood ctDNA Assay May Predict Outcomes for Patients with Newly Diagnosed Multiple Myeloma Post-AHCT

Among newly diagnosed patients with multiple myeloma who have undergone autologous stem cell transplantation (AHCT), a tumor-informed circulating tumor DNA (ctDNA) assay utilizing archival blood samples appears to be predictive of outcomes, according to data from a poster presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results from the study identified that 70.8% of patients who were pre-AHCT were Signatera-positive for minimal residual disease (MRD) vs 53.6% of patients 3 months post-AHCT and 39.2% of patients who were receiving maintenance therapy. Additionally,, relapse rates for patients following AHCT included 55.5% for patients who were flow negative and 68.4% for patients who were flow positive, as well as 30.7% and 93.3% (HR, 5.6; 95% CI, 1.8-17; P = .0003). for those who were Signatera-negative and Signatera-positive, respectively.

Those who who were negative for ctDNA at 3 months following AHCT achieved a significantly superior median progression-free survival (PFS; 84 months) compared with patients who tested positive for ctDNA at 3 months after AHCT (31 months; P = .003).

“Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation, [patients with] multiple myeloma invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker,” the investigators wrote in regard to the rationale for the research.

In the retrospective, single center study, investigators assessed ctDNA MRD in blood samples from 28 patients with multiple myeloma following up front treatment with AHCT. After a median follow-up of 92.4 months (range, 24.5-119.5), a total of 80 plasma time points were available both pre- and post-AHCT.

Level 10-4 multiparameter flow cytometry (MFC) was utilized to examine MRD from bone marrow biopsy. Moreover, the research team performed MRD assessments at 3 months post-AHCT through tumor-informed ctDNA analysis. ctDNA’s prognostic value was analyzed by correlating MRD status with clinical outcomes through the use of cox regression.

Median patient was 67 years (range, 41-75) and 57.1% of patients included were male. A number of isotypes were reported on the study, including IgG kappa/lambda (71%), IgA kappa/lambda (11%), and light chain (18%). The majority of patients had stage I disease (54%), with a minority of patients who had stage II (39%), III (3.5%), and unknown disease (3.5%). A total of 14% of patients had high-risk cytogenetics. Induction therapies included bortezomib, lenalidomide (Revlimid), and dexamethasone (46%); cyclophosphamide, bortezomib and dexamethasone (39%); or another treatment (15%).

A total of 50% of patients experienced a complete or near complete response following transplantation. Additionally, 18% and 32% of patients achieved a very good partial response (PR) or PR, respectively, after undergoing AHCT.

Additional findings from the study highlighted a positive predictive value for relapse of 93.3% for patients who tested positive for ctDNA at 3 months after AHCT, which was significantly higher than the value observed for marrow MFC (68.4%).

“Future prospective studies with real-time marrow [next-generation sequencing] and ctDNA samples are needed to define the role of ctDNA in multiple myeloma and its prognostic significance,” the study’s authors concluded

Reference

Dhakal B, Sharma S, Shchegrova S, et al. Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma. J Clin Oncol. 2021;39(suppl 15):abstr 8029. doi:10.1200/JCO.2021.39.15_suppl.8029