Will Mass Spectrometry Replace Current Techniques for Both Routine Monitoring and MRD Detection in Multiple Myeloma?
Round 1
Reviewer 1 Report
This review aimed to answer the question if mass spectrometry may substitute conventional methodology for follow-up and MRD in myeloma. However the author does not discuss MRD at all and provides no evidence for the role of mass spectrometry in MRD. MRD methodology according to IMWG criteria is not discussed at all. If there are no data on MRD this has to be removed from the title.
Author Response
Section 3.1 is about the role of mass spectrometry in MRD testing. IMWG-specified MRD tests were discussed (ex. next generation sequencing (NGS) analysis of bone marrow). I have made some revisions in the text to clarify.
Reviewer 2 Report
This is a concise, well-written review of an important topic in in the clinical management of multiple myeloma. Protein electrophoresis and immunofixation are the current standard-of-care serologic detection method for myeloma. yet, significant improvements in sensitivity of disease detection with next-generation methods testing bone marrow biopsy samples introduces new discrepancies in the monitoring and detection of trace levels of residual disease. This review nicely highlights the advantages and also the further obstacles related to the development and future implementation of mass spectrometry-based paraprotein measurements as a superior technique as compared to protein eletrophoresis and immunofixation.
Major concerns: None
Minor points:
- May be worthwhile to at least comment on the impact of immunoglobulin half-life on interpretation of results especially in setting of an MRD-negative bone marrow biopsy.
- The author introduces the idea of integrating mass spectrometry into the MRD assessment algorithm for myeloma, but it could be beneficial to discuss how this would require a further adaptation of the process, similar to the brief comparison offered of MALDI-TOF versus LC-HRMS.
Author Response
Thank you for your time in reviewing my paper. Please see my responses to your points:
1. May be worthwhile to at least comment on the impact of immunoglobulin half-life on interpretation of results especially in setting of an MRD-negative bone marrow biopsy.
- Thank you for your suggestion. I have added a few sentences (lines 62-65) regarding how the long half-life may confound results.
2. The author introduces the idea of integrating mass spectrometry into the MRD assessment algorithm for myeloma, but it could be beneficial to discuss how this would require a further adaptation of the process, similar to the brief comparison offered of MALDI-TOF versus LC-HRMS.
- I added the following comment to the end of section 3.1: “Down the road, it will also be important to consider practical factors that affect the incorporation of these assays into MRD testing algorithms like the complexity of these tests, the cost/benefit of using mass spectrometry versus other techniques, and the best timing of these assays.”
Round 2
Reviewer 1 Report
The authors adequately addressed my comments
