Aberrant Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts, Assessed by Next-Generation Flow Cytometry, Is a Negative Predictor for Deep Response Post Autologous Transplantation in Multiple Myeloma; A Prospective Study in 199 Patients.

Abstract

Simple SummaryAutologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients. However, despite its overall benefit, patients undergo various clinical outcomes post ASCT. Therefore, the identification of biomarkers that could explain, at least partially, this heterogeneity is of utmost clinical significance. The aim of this study was to assess clonal plasma cell contamination of the stem cell grafts of NDMM and evaluate its potency as a predictive/prognostic marker. Our results showed that worse responses to induction therapy correlate with higher levels of graft contamination. Importantly, our data revealed the significantly higher risk of delaying or not achieving complete remission and minimal residual disease (MRD)-negative responses among patients with graft contamination. Graft contamination is emerging as a promising predictive biomarker of clinical relevance that could be used to stratify patients post ASCT.High-dose chemotherapy with autologous stem cell support (ASCT) is the standard of care for eligible newly diagnosed Multiple Myeloma (MM) patients. Stem cell graft contamination by aberrant plasma cells (APCs) has been considered a possible predictive marker of subsequent clinical outcome, but the limited reports to date present unclear conclusions. We prospectively estimated the frequency of graft contamination using highly sensitive next-generation flow cytometry and evaluated its clinical impact in 199 myeloma patients who underwent an ASCT. Contamination (con+) was detected in 79/199 patients at a median level 2 × 10−5. Its presence and levels were correlated with response to induction treatment, with 94%, 71% and 43% achieving CR, VGPR and PR, respectively. Importantly, con+ grafts conferred 2-fold and 2.8-fold higher patient-risk of not achieving or delaying reaching CR (4 vs. 11 months) and MRD negativity (5 vs. 18 months) post ASCT, respectively. Our data also provide evidence of a potentially skewed bone marrow (BM) reconstitution due to unpurged grafts, since con+ derived BM had significantly higher prevalence of memory B cells. These data, together with the absence of significant associations with baseline clinical features, highlight graft contamination as a potential biomarker with independent prognostic value for deeper responses, including MRD negativity. Longer follow-up will reveal if this corresponds to PFS or OS advantage.