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.

Prognostic Value of Association of Copy Number Alterations and Cell-Surface Expression Markers in Newly Diagnosed Multiple Myeloma Patients

“…In the group without adverse CNAs ( n = 29), only patients with no genetic alterations were included (thus seven patients who had only HRD without other adverse CNAs were excluded). The presented results are consistent with the data presented previously by other studies [ 39 , 40 , 41 ].…”

A Case of Plasmablastic Multiple Myeloma With Extramedullary Disease Manifesting as a Myelomatous Pleural Effusion

“…Cytologic markers considered high risk that were identified in our patient included a deletion of the short arm of chromosome 17, a gain of function in chromosome 1q, and a monosomy 13. Deletion of 17p is seen in 5-10% of patients with MM and is associated with TP53 gene mutations [ 10 , 11 ]. A gain of function in chromosome 1q is a common genetic mutation, found in 40% of MM patients at diagnosis.…”

Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

“…The old, current, and future therapeutic modalities in MM are shown in [14][15][16][17][18][19] treatment; (8) advanced disease, stage III; and ( 9) frailty [16,20]. In patients with HR-MM (double-hit or triple-hit myeloma), it is recommended to adopt the following line of treatment, induction therapy with 3-4 cycles of VRd followed by autologous HSCT, and then maintenance therapy with bortezomib-based regimen, that is, bortezomib every 2 weeks or low-intensity VRd regimen till disease progression [1,[20][21][22][23]. Alternatively, patients can be treated with either (1) 3-4 cycles of KRd followed by early autologous HSCT, followed by carfilzomib-based or bortezomib-based maintenance therapy, or (2) the combination of daratumumab + VRd [16,20,[22][23][24][25].…”