Melphalan-prednisone-bortezomib improves HRQoL in intermediate-fit and frail NDMM patients

Treatment with melphalan-prednisone-bortezomib (MPV) improves health-related quality of life (HRQoL) in both intermediate-fit and frail newly diagnosed multiple myeloma (NDMM) patients, according to the results of the prospective phase II HOVON123 trial.

Approximately 60 percent of older patients with newly diagnosed NDMM are intermediate-fit or frail, as assessed by the International Myeloma Working Group (IMWG) frailty score. [Lancet Healthy Longev 2022;3:e628-e635] While frailty is known to be associated with a higher incidence of non-haematological toxicity and discontinuation of therapy, longitudinal data on whether and to what extent frailty affects HRQoL are lacking. [Blood 2015;125:2068-2074] “As older multiple myeloma patients prefer HRQoL over length of life, these data are necessary for sensible shared treatment decision-making in intermediate-fit and frail patients,” wrote the researchers. [Ann Oncol 2018;29:1718-1726; J Clin Oncol 2018;36:2018]

The present secondary analysis of the HOVON123 trial included 137 frail and 71 intermediate-fit patients aged ≥75 years. Patients were treated with nine cycles of dose-adjusted MPV: melphalan 6 mg/m² and prednisone 30 mg/m² on days 1–4 and bortezomib 1.3 mg/m² on days 1, 8, 15, and 22 of each 35-day cycle. Patients were followed up for 12 months after treatment completion (12MaT). [Eur J Cancer 2024;doi:10.1016/j.ejca.2024.114153]

Frail patients had a lower baseline global health status (p<0.001), worse physical functioning (p<0.001), more pain (p=0.001), and more fatigue (p<0.001) compared with intermediate-fit patients. At the same time, future perspective, constipation, diarrhoea, treatment side effects, and peripheral neuropathy (PNP) complaints were similar between both groups at baseline.

In both groups, there was an improvement over time in global health status (frail: p<0.001; intermediate-fit: p=0.001) and future perspective (both groups: p<0.001). In frail patients, additional improvements were observed in three HRQoL subscales: physical functioning (p<0.001), fatigue (p<0.001), and pain (p<0.001). PNP complaints worsened over time in both groups (frail: p<0.001; intermediate-fit: p=0.001). “While PNP complaints worsened from 9MaT in both groups, the mean score for PNP complaints returned approximately to baseline at 12MaT for intermediate-fit patients, while no recovery was observed in frail patients,” added the researchers.

Global health status improved earlier in frail than in intermediate-fit patients: between 3 months of treatment (3MoT) and 12MaT in frail patients vs between 9MoT and 6MaT in intermediate-fit patients. Likewise, improvement in pain was achieved earlier in frail patients: from 3MoT onwards in frail patients vs from 9MoT in intermediate-fit patients. Only frail patients reached an improvement in physical functioning between 3MoT and 6MaT and fatigue between 9MoT and 6MaT. However, both parameters fell below the baseline at 12MaT.

“Frail patients show faster and larger improvements in HRQoL outcomes during treatment with MPV compared with intermediate-fit patients, and these improvements in HRQoL outcomes persist during post-treatment follow-up. Physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration,” concluded the researchers.

“HRQoL studies are potentially hindered by a ‘survivorship bias’,” they noted. [Epidemiol Psychiatr Sci 2021;30e45] “In our study, only patients who completed the full nine cycles of MPV and who did not yet start second-line treatment were included in the follow-up analysis. These patients were in remission and therefore may have had a low disease burden and potentially superior HRQoL compared with those who were excluded prematurely.”