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

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.

The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells

“…PCL patients were treated with various regimens. NDMM patients, evaluated for the presence of CPCs (n = 161, see below for details), were treated with either bortezomib, lenalidomide, dexamethasone (VRD) or bortezomib, cyclophosphamide, or dexamethasone (VCD) as induction regimens followed by high-dose melphalan (HDM) with autologous stem cell transplantation (ASCT), according to the protocol described in detail elsewhere [ 16 ]. The number of CPCs and the proportion of patients bearing high-risk aberrations were equally distributed between the two treatment groups (data not shown).…”

Impact of interval progression before autologous stem cell transplant in patients with multiple myeloma

“…The presence of IP is also of additional significance because the collection of stem cells occurs during this time. A recent, prospective study showed MM cells in 40% of the collected stem cells, with the frequency of contamination and re-infusion directly correlating with the post-induction response and conferring a 2-fold risk increase in not achieving or delaying CR post-HDT/ASCT ( 23 ).…”

Treatment Strategy for Ultra-High-Risk Multiple Myelomas with Chromosomal Aberrations Considering Minimal Residual Disease Status and Bone Marrow Microenvironment

“…In the MASTER trial, the MRD negativity rate after D-KRd induction therapy was lower in patients with UHRCAs than in the other CA groups, indicating that the myeloma cells are more frequently contaminated in the former than in the latter [6]. In two clinical studies, the MRD status of the autograft correlated with the survival time after ASCT [49,50]. Therefore, we discuss the role of MRD eradication in autografts in achieving persistent MRD negativity, particularly in patients with UHRCAs.…”