Multiple myeloma with high-risk cytogenetics and its treatment approach

Abstract

Despite substantial advances in anti-myeloma treatments, early recurrence and death remain an issue in certain subpopulations. Cytogenetic abnormalities (CAs) are the most widely accepted predictors for poor prognosis in multiple myeloma (MM), such as t(4;14), t(14;16), t(14;20), gain/amp(1q21), del(1p), and del(17p). Co-existing high-risk CAs (HRCAs) tend to be associated with an even worse prognosis. Achievement of sustained minimal residual disease (MRD)-negativity has recently emerged as a surrogate for longer survival, regardless of cytogenetic risk. Information from newer clinical trials suggests that extended intensified treatment can help achieve MRD-negativity in patients with HRCAs, which may lead to improved outcomes. Therapy should be considered to include a 3- or 4-drug induction regimen (PI/IMiD/Dex or PI/IMiD/Dex/anti-CD38 antibody), auto-transplantation, and consolidation/maintenance with lenalidomide ± a PI. Results from ongoing clinical trials for enriched high-risk populations will reveal the precise efficacy of the investigated regimens. Genetic abnormalities of MM cells are intrinsic critical factors determining tumor characteristics, which reflect the natural course and drug sensitivity of the disease. This paper reviews the clinicopathological features of genomic abnormalities related to adverse prognosis, focusing on HRCAs that are the most relevant in clinical practice, and outline current optimal therapeutic approaches for newly diagnosed MM with HRCAs.

Keywords: Multiple myeloma; del(17p); del(1p); gain/amp(1q21); t(14;16).

Fig. 1

Treatment approach for patients with newly diagnosed multiple myeloma and high-risk cytogenetic abnormalities. MM multiple myeloma, ASCT autologous stem cell transplant, d dexamethasone, Dara daratumumab, FISH fluorescent in situ hybridization, K carfilzomib, R lenalidomide, V bortezomib, HRCA high-risk cytogenetic abnormality, MRD minimal residual disease

Fig. 2

Proportion of achievement of MRD-negativity (MRD, 10^–5) by treatment phase and the number of HRCA in the MASTER trial. The negativity rates increased from post induction to consolidation in all subgroups [45]. MRD minimal residual disease, HRCA high-risk cytogenetic abnormality, ASCT autologous stem cell transplantation