Traditional response assessment criteria for multiple myeloma (MM) treatment are surrogate measures that rely on the detection of paraprotein in serum or urine. Recent advances in therapy are promoting the development of new technologies to detect smaller amounts of residual disease, which represents a unidimensional, direct measure of disease burden. Thus, the ability to detect measurable residual disease (MRD) at a sensitivity of 1 in 106 cells raises new questions about using MRD to inform disease management.
In a recent review published in the British Journal of Haematology, Luciano Costa, MD, PhD, of the division of hematology and oncology at the University of Alabama at Birmingham, and colleagues discussed the challenges and opportunities that accompany the use of MRD in MM.1
“These are great times for the myeloma research community and patients [with myeloma]. We have seen, and are still seeing, a revolution in therapies, and as the therapies improve, I think it’s only reasonable that we also improve our diagnostic methods because now it becomes relevant to measure and assess disease at a level that was never meaningful before [when] the therapies were just not adequate,” Dr Costa said in an interview with Hematology Advisor.
Until recently, first-generation flow cytometry (4 to 8 colors) was primarily used to detect MRD to a limit of 10-4. However, patients whose disease was in complete remission and who were considered to be MRD-negative still experienced relapse. This prompted the development of more sensitive detection assays.
Both the EuroFlow™ consortium and researchers at Memorial Sloan Kettering Cancer Center (MSKCC) have developed next-generation flow (NGF) cytometers. The EuroFlow™ NGF uses 2 flow cytometry tubes, each with 8 antibodies, while the MSKCC cytometer uses a 10-color, single tube method. Both of the NGF cytometers have comparable results with limits of detection at 2 x 10-6 for the EuroFlow™ and 6 x 10-6 for the MSKCC 10-color NGF.2
An alternative approach for MRD detection is next-generation sequencing using the clonoSEQ® platform, which was cleared by the US Food and Drug Administration for use in patients with MM in 2018. This platform identifies and quantifies the rearranged immunoglobulin heavy chain and kappa and lambda sequences and has a 6.8 x 10-7 limit of detection.
“Having this new ability to measure disease opens up several opportunities that we didn’t have before — for instance, being able to deploy novel therapies early in the natural history of the disease based on the fact that the patient has not reached a certain depth of remission,” said Dr Costa.