New risk prediction model for MM outcomes proves easy to use and implement in clinical practice

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A novel frailty-based outcome prediction model for multiple myeloma (MM) has proven to be an easy-to-use tool in clinical practice and has produced valid results based on a large cohort of real-world patients with a new diagnosis of MM, according to a recent study.

A new frailty-based outcome prediction model for multiple myeloma (MM) has proven to be an easy-to-use tool in clinical practice and has produced valid results based on a large cohort of real-world patients in the UK United, according to a recent study.

The retrospective study published in PLoS Onewas the first to assess clinical outcomes by myeloma risk profile (MRP) in a real-world high-risk cohort of patients who were treated with VCD-based proteasome inhibitors (bortezomib [Velcade]/cyclophosphamide/dexamethasone).

“Further evaluation of MRP in the real world when continuous therapies are used may further strengthen its prognostic role in elderly patients with myeloma,” the researchers wrote.

Achieving optimal outcomes for myeloma is difficult because patients often present with the disease in older age, organ dysfunction, comorbidities and frailty, the authors noted. The increased toxicity burden may cause providers to reduce doses or discontinue treatments for patients with MM. For this reason, the focus of clinical practice has shifted to reducing the risk of undertreating fit patients and overtreating frail patients.

Other risk prediction models, such as the International Myeloma Working Group and the Revised Myeloma Comorbidity Index, have been validated but may have limitations as they can be time consuming.

Additionally, “there remains an ongoing debate about whether current frailty assessments, such as MRP, need to be further harmonized prior to their implementation in myeloma treatment decision-making in healthcare.” routine, such as the inclusion of biomarkers for aging and other parameters reflecting baseline patient-related characteristics,” the investigators said.

They conducted an analysis to validate the use of MRP in patients with newly diagnosed MM who were ineligible for transplantation. To be included in the study, patients had to have symptomatic MM requiring routine first-line treatment and not be eligible for stem cell transplantation due to advanced age or comorbidities. All patients had to be treated within the UK Thames Valley Cancer Network with at least 1 cycle of VCD chemotherapy.

A total of 158 patients treated with VCD therapy between June 2012 and December 2018 were identified, and 100 were included in the final cohort. Patients’ overall MRP scores were calculated and were categorized into 1 of 3 fitness groups,

  • Fragile: scores greater than -0.0283
  • Intermediate fitness: scores between –0.256 and –0.0283
  • Adjustment: scores less than -0.256

Overall, 62 of the patients were classified as frail, 27 were of intermediate fitness, and 11 were considered fit. The analysis focused on frail (n=62) vs non-frail (n=38) patients. The median age of the entire cohort was 76 years and 53% were male.

Patients in the fragile group were older and had lower progression-free survival with a higher median C-reactive protein value. A higher proportion of frail patients had to discontinue treatment due to disease progression compared to physically fit or intermediate patients: 19.4% versus 15.8%.

The overall response rate for the entire cohort was 75% and was comparable between subgroups. There were 222 adverse events (AEs) experienced by 80 patients. The median total number of AEs of any grade per patient in the total cohort was 2. A higher incidence of AEs was observed in the frail subgroup (85.5%) compared to the non-frail subgroup (71.1%).

The study had some limitations, including small sample size, potential for confounding and patient selection bias, and possible misinterpretation of medical records and under-reporting of toxicities.

Reference

Djebbari F, Rampotas A, Panitsas F, et al. Assessment of frailty characteristics and clinical outcomes according to the new frailty-based outcome prediction model (Myeloma Risk Profile-MRP) in a British cohort of elderly patients newly diagnosed with myeloma. PLOS ONE. Published online January 11, 2022. doi:10.1371/journal.pone.0262388

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