An increasing percentage of patients with multiple myeloma (MM) reach a state of minimal residual disease (MRD). Several strategies for MM MRD-monitoring are available, such as allele-specific oligonucleotide qPCR (ASO-qPCR), next-generation sequencing (NGS) and mass spectrometry (MS). These methods rely on the presence and the stability of the unique immunoglobulin molecular fingerprint derived from the clonal plasma cell population. Moreover, for MS-MRD monitoring it is imperative that MS-compatible clonotypic M-protein peptides are identified. To support implementation of molecular MRD techniques, we studied the presence of these clonotypic features in the MM genomic CoMMpass-database. An analysis pipeline was constructed to identify unique clonal molecular fingerprints and their derived clonotypic peptides based on transcriptomic datasets. A proof of concept study revealed the detection of these clonotypic peptides by MS. We demonstrate that in a cohort of 609 MM patients, multiple unique clonotypic peptides compatible with MS measurements could be identified for all patients. Furthermore, the clonal immunoglobulin gene (Ig)-fingerprints of both the light- and heavy chain remained stable during MM disease progression. In conclusion, our data support the use of the clonal Ig-fingerprint in MM patients as a suitable MRD target for molecular profiling techniques such as ASO-qPCR, NGS and MS-MRD analyses

Clonotypic peptides were based on RNA-seq derived clone assemblies from the three MM cell lines. Targeted assays were developed based on SIL-peptide counterparts of the clonotypic peptide sequence. As a positive control a lambda light chain constant peptide was included. The growth medium was subsequently enriched for immunoglobulins and the presence the endogenous clonotypic peptide was determined for each cell line with the targeted assays.

Enriched immunoglobulins from the growth medium of cell lines