The New York researchers conducted a similar study of SMM patients treated at Memorial Sloan Kettering Cancer Center. At 1-, 2-, 5- and 10-years, the low-risk group had progression rates of 1.3%, 4.8%, 12.2% and 28.9% compared to 7.6%, 12.1%, 34.1% and 40.4% for the intermediate-risk group. Even high-risk patients had lower progression rates than historically assumed at 16%, 34.8%, 66.7% and 83.2% for the same intervals.3 “These findings indicate that SMM overall may be more indolent than previously appreciated. As early- intervention strategies continue to expand for patients with high-risk SMM, there is a pressing need for more refined tools that reliably identify those most likely to benefit from treatment,” the New York team wrote. Greater Need for Later Line MM Therapies With SMM removed from the data, the need for more therapeutic options to truly extend life expectancy for those with symptomatic MM comes into clearer focus. Fortunately, new therapies have recently gained approval, offering improved options for those whose dis- ease has become refractory to multiple agents. For transplant-ineligible or deferred patients, NCCN category 1 preferred regimens include daratumumab with lenalidomide and dexamethasone, with quadruplet regi- mens of VRd plus either daratumumab or bisatuximab for nonfrail patients younger than 80 years. Other frontline therapies combine proteasome inhibitors, immunomod- ulatory drugs (IMiDs), monoclonal antibodies (mABs) and dexamethasone. Treatment selection at relapse either following HCT or in patients ineligible for HCT must consider prior therapies, depth and duration of response, comorbidities, frailty and patient preferences.4 By the third line, however, most patients will prove refractory to multiple PIs, IMiDs and mABs. Consequently, NCCN recommends CAR T-cell therapy, with ciltacabtagene autoleucel preferred for patients who have received one prior line of therapy, including an IMiD and a PI and who are refractory to lenalidomide and idecabtagene vicleucel for those who have had two or more prior lines, including an IMiD, an anti-CD 38 mAb and a PI. Powerful Options in Later Lines Provide Hope As patients experience repeated relapses, they may lose hope and see less point in continuing treatment. A study by researchers at the VA North Texas Health Care System and Texas Tech University Health Sciences Center, among others, found an attrition rate between 2000 and 2020 of 50.3% among Black veterans and 56.5% among white veterans between the first and second lines of therapy and attrition rates of 52.4% for Black and 57.8% for white veterans between the sec- ond and third lines. Notably, however, receipt of three or more lines of therapy was associated with 17.5% increased overall survival. 5 The emergence of bispecific T-cell engagers (BiTEs) as options in the fourth and subsequent lines can provide hope for these patients, with the most recently approved agent, linvoseltamab, offering overall survival rates of more than 31 months and objective response rates north of 70%. In BiTEs for MM, one arm of the antibody binds to the CD3 antigen on the tumor-specific T cells and the other arm binds to either the BCMA or GPRC5D antigen on the myeloma cell. So far, four BiTEs have received FDA approval and NCCN recommendation for use in the fourth and subsequent lines. Three gained approval in 2022 and 2023: teclistamab and elrantamab, which both target BCMA, and talquetamab, which tar- gets GPRC5D. The phase I/II MajesTEC-1 trial showed that 63% of heavily pretreated patients responded and 39.4% achieved a complete response to teclistamab, leading to its FDA approval for MM patients who had received four or more lines of therapy. Overall, 26.7% demon- strated no minimal residual disease (MRD), which rose to 46% among complete responders. Median duration of response (DOR) was 18.4 months and the median dura- tion of progression-free survival (PFS) was 11.3 months.6 The phase II MagnetisMM-3 trial provided the evi- dence for approval for elranatamab for use in patients whose cancer had stopped responding or had progressed after at least four previous therapies. At 33.9 months of follow-up, elranatamab produced an objective response 3 0 Cumulative Incidence of Progression, Stratified by GLP-1 Receptor Agonist Use Status of the Overall Cohort Source: Association between glucagon-like peptide-1 receptor agonist use and progression of monoclonal gammopathy of uncertain significance to multiple myeloma among patients with diabetes. JNCI Cancer Spectr. 2024 Nov 1;8(6):pkae095. doi: 10.1093/jncics/pkae095. PMID: 39514091; PMCID: PMC11643351.
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