Mass-Fix better predicts for PFS and OS than standard methods among multiple myeloma patients participating on the STAMINA trial (BMT CTN 0702 /07LT)

Abstract

Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses are associated with better progression free survival (PFS) and overall survival (OS). To test the hypothesis that Mass-Fix, a mass spectrometry-based means to detect monoclonal proteins, is superior to existing methodologies to predict for survival outcomes, samples from the STAMINA trial (NCT01109004), a trial comparing three transplant approaches, were employed. Samples from 575 patients from as many as three time points (post-induction [post-I; pre-maintenance [pre-M]; 1 year post enrollment [1YR]) were tested when available. Four response parameters were assessed: Mass-Fix, serum immunofixation, complete response, and measurable residual disease (MRD) by next generation flow cytometry. Of the four response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses. Although MRD drove Mass-Fix from the model for PFS at post-I and pre-M, 1YR Mass-Fix was independent of 1YR MRD. For OS, the only prognostic pre-I measure was Mass-Fix, and the only 1YR measures that were prognostic on multivariate analysis were 1YR MRD and 1YR Mass-Fix. SIFE and CR were not. Mass-Fix is a powerful means to track response.

The potential role of mass spectrometry for the identification and monitoring of patients with plasma cell disorders: Where are we now and which questions remain unanswered?

“…The potential complementary role that MS-based assays may have in MRD monitoring in myeloma remains an active area of research but initial studies show promising results for the prognostic significance of MALDI-TOF MS-based response assessments. 67,84 Comparisons should also be made against other peripheral blood-based techniques for the detection of MRD which are being developed, such as circulating tumour DNA and flow cytometry for the detection of circulating tumour cells. This is particularly important as the former can provide additional information about the genetic composition of residual disease that may help optimise subsequent therapeutic interventions, may be a more clinically relevant strategy.…”

“…The potential complementary role that MS‐based assays may have in MRD monitoring in myeloma remains an active area of research but initial studies show promising results for the prognostic significance of MALDI‐TOF MS‐based response assessments 67,84 . Comparisons should also be made against other peripheral blood‐based techniques for the detection of MRD which are being developed, such as circulating tumour DNA and flow cytometry for the detection of circulating tumour cells.…”

“…low cost and widely available methodology for monitoring response but they have limited sensitivity and recent studies have questioned their prognostic utility in light of the deep responses obtained with modern treatment regimens. 83,84 BM-based MRD assays provide greater sensitivity for MRD detection; however, the need for invasive BM sampling and their associated cost limits testing frequency. In a study of 187 patients treated in the GEMMENOS65 trial, Puig et al demonstrated that MALDI-TOF MS has a high negative predictive value (NPV) when NGF is used as the reference; the NPV of MALDI-TOF MS post consolidation per MRD range was 97%, 89% and 85% for ≥1 × 10 −4 , ≥1 × 10 −5 to 1 × 10 −4 and ≥1 × 10 −6 , respectively.…”

“…The costs and practical considerations for the methodologies that are currently approved by the IMWG to assess therapeutic responses in patients with PCD are outlined in Table 2. The electrophoretic techniques provide a relatively low cost and widely available methodology for monitoring response but they have limited sensitivity and recent studies have questioned their prognostic utility in light of the deep responses obtained with modern treatment regimens 83,84 . BM‐based MRD assays provide greater sensitivity for MRD detection; however, the need for invasive BM sampling and their associated cost limits testing frequency.…”

Minimal Residual Disease in Multiple Myeloma—Current Approaches and Future Clinical Implications

“…Mass spectroscopy using either MALDI-TOF or liquid chromatography (LC-MS) has significantly higher sensitivity for detecting monoclonal proteins compared to serum electrophoresis [63,69]. Mass spectroscopy has been found to have similar sensitivity and a high level of concordance when compared to bone marrow based MRD assessments [63,64,69,70]. There are current efforts for validation of V(D)J sequencing for MRD evaluation of peripheral blood samples rather than bone marrow samples.…”