High-risk multiple myeloma (MM) is a challenging condition to diagnose and treat, requiring effective tools to identify patients and deliver targeted therapies. The International Staging System (ISS) and its revised version (R-ISS) stratify risk using serum markers and chromosomal abnormalities like del(17p), t(4;14), and high lactate dehydrogenase levels, which predict worse outcomes. Newer systems like the R2-ISS include additional markers such as 1q copy number alterations, enhancing prognostic accuracy. Despite the use of proteasome inhibitors, immunomodulatory drugs, and stem cell transplantation, high-risk patients often face rapid disease progression and poor prognosis.

For high-risk, newly diagnosed MM, treatment typically involves induction therapy, autologous stem cell transplantation, and maintenance. However, outcomes remain suboptimal, prompting trials of more intensive regimens, including monoclonal antibodies like daratumumab and elotuzumab. CAR T-cell therapies and bispecific antibodies targeting BCMA show promise, as do therapies targeting specific mutations like t(11;14) with venetoclax or BRAF inhibitors. These newer treatments offer potential improvements, but further studies are needed to determine the optimal approach and integration into clinical practice.

Reference: Caro J, Al Hadidi S, Usmani S, et al. How to Treat High-Risk Myeloma at Diagnosis and Relapse. Am Soc Clin Oncol Educ Book. 2021;41:291-309. doi: 10.1200/EDBK_320105.