IMW 2019 | Management of elderly patients with multiple myeloma

During the XVII International Myeloma Workshop (IMW) meeting in Boston, US, Sonja Zweegman and Alessandra Larocca presented an educational session entitled: “Management of Elderly Patients with Multiple Myeloma (MM)”.¹ The current treatment options for frail patients were discussed, along with classification systems, and potential future directions for therapies.¹

Classification of frailty in MM

• The International Myeloma Working Group (IMWG) classification:²
  • Includes evaluation of activities of daily living (ADL)
  • Indicates a higher incidence of functional, cognitive, mental and nutritional impairments in patients who are frail, compared to those who are unfit
  • Therefore, the IMWG score is considered to reflect biological frailty
• The revised Myeloma Comorbidity Index (R-MCI) quantifies comorbidities and adds disease characteristics:³
  • Includes assessment of age (≤ 60 vs 60–70 vs > 70 years), lung function, Karnofsky performance score (KPS), physician assessment of frailty, renal function by glomerular filtration rate (GFR) and cytogenetics³
  • May be more discriminative¹
  • However, the R-MCI was only evaluated in a population of German patients with MM^1,3
• Another method of assessing frailty is the Myeloma Risk Profile (MRP), which uses the World Health Organization (WHO) performance status, age, international staging system (ISS) and C-reactive protein (CRP) levels⁴
  • The MRP has been shown by Cook et al., in the Myeloma IX trial to be associated with outcome⁴

Also, at the IMW meeting, Ho Sup Lee presented an analysis of the outcomes of patients treated with bortezomib (V)-based regimens, by frailty scoring systems. The group found that patients who were classified as frail by IMWG criteria, or high-risk by R-MCI criteria, had a shorter survival compared to patients who were not frail, or who were deemed low-risk. The R-MCI criteria was more accurately able to predict survival compared to IMWG, however R-MCI is less easy to implement, indicating a requirement for a more simplified and predictable frailty risk model to use in clinical practice. Read more about this study below.⁵

Clinical questions

Elderly and frail patients are often excluded from clinical trials, therefore clinical data on this population is lacking.⁵ When treating elderly patients, several factors should be considered;¹

• Are the patients fit, unfit or frail (depending upon classification system used)?
• What is the optimal drug regimen? Is it a doublet, triplet or quadruplet therapy?
• Is the patient eligible for autologous stem cell transplant (ASCT)?
• Duration of therapy; how many induction cycles should be used?
• Does the dose of the chosen medication(s) need to be modified? If so, how?
• Many elderly patients do not progress to later lines of treatment, and the treatment duration and treatment-free intervals decrease with each subsequent line of therapy⁶
• Therefore, response to first-line treatment is crucial⁶

Treatment options

The current treatment paradigm for elderly patients with MM is shown in Table 1.

Table 1. Frontline treatment of elderly patients with MM¹

Outcomes of patients treated with V-based regimens, by frailty scoring systems⁵

Also during the XVII IMW meeting, Ho Sup Lee, Kosin University College of Medicine, Busan, KR, presented an evaluation of the clinical impact of frailty on outcomes in transplant ineligible MM patients treated with V-based chemotherapy as frontline treatment. Additionally, the authors compared the IMWG and R-MCI frailty scoring systems.

This retrospective study analyzed the outcomes of 366 patients (median age: 69 years) treated in South Korea between 2007 and 2017. Patients received VMP as frontline therapy, and were classified according to the IWMG (fit, unfit, frail) or R-MCI (low-, intermediate- or high-risk) criteria. For the IMWG criteria, ADL/instrumental ADL was substituted for Eastern Cooperative Oncology (ECOG) scores. More patients were classified as frail by IMWG criteria (43.4%) compared to high-risk by R-MCI criteria (13.7%).

The median PFS and OS for the total cohort, and for each frailty group, are shown in Table 2. When comparing frailty classification for PFS and OS by IMWG or R-MCI criteria, all were statistically significant (p< 0.001).

Table 2. PFS and OS by frailty score

Using a cox proportional hazard model for PFS and OS, this analysis found that only classification system was significantly associated with PFS (for both IMWG and R-MCI), whilst for OS, age was  significant for both classification systems, though classification system was only significant for R-MCI.

Conclusion

Patients who were classified as frail by IMWG criteria, or high-risk by R-MCI criteria, had a shorter survival compared to patients who were not frail, or who were deemed low-risk. The R-MCI criteria was more accurately able to predict survival compared to IMWG, however, due to the number of variables measured, R-MCI is less easy to implement. Therefore, there is a requirement for a more simplified and predictable frailty risk model to use in clinical practice.