This study aimed to assess the predictive role of a baseline geriatric assessment (GA) in elderly newly diagnosed multiple myeloma (MM) patients. ​ A pooled analysis of 869 individual patient data from 3 prospective trials was conducted. ​ The GA consisted of three tools: the Katz Activity of Daily Living (ADL), the Lawton Instrumental Activity of Daily Living (IADL), and the Charlson Comorbidity Index (CCI). ​ An additive scoring system based on age, comorbidities, and cognitive and physical conditions was developed to identify three groups: fit, intermediate fitness, and frail. ​ The study found that the frailty score predicted overall survival (OS) and the risk of toxicity in elderly myeloma patients. ​ The 3-year OS was 84% in fit, 76% in intermediate-fitness, and 57% in frail patients. ​​ The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness, and 34.0% in frail patients. ​ The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness, and 31.2% in frail patients. ​​ The International Myeloma Working Group proposes this frailty score for the measurement of frailty in designing future clinical trials. ​

Important Points:

1. Multiple myeloma predominantly affects elderly patients, with over 60% of diagnoses and 75% of deaths occurring in those over 65 years of age. ​
2. Elderly patients benefit less from new treatments, likely due to increased treatment-related toxicity and worse biology.
3. Frail patients are underrepresented in clinical trials, and the role of new drugs in these patients is relatively unknown. ​
4. The European Medicines Agency requires postmarketing safety studies in the older population. ​
5. The choice of multiple myeloma treatment is primarily based on chronologic age and performance status, but physical and cognitive functions can vary greatly among adults of the same age. ​
6. Frailty is a state of cumulative decline in physiological systems, resulting in a diminished resistance to stressors like cancer and its treatment. ​
7. The Comprehensive Geriatric Assessment (CGA) is a multidisciplinary patient evaluation with validated tools that can contribute to defining the frailty profile. ​
8. The CGA is not routinely performed in hematology because it is complex and time-consuming. ​
9. The study assessed the predictive role of a baseline GA in 869 elderly newly diagnosed MM patients. ​
10. An additive scoring system based on age, comorbidities, and cognitive and physical conditions was developed to identify three groups: fit, intermediate fitness, and frail. ​
11. The frailty score predicted overall survival (OS) and the risk of toxicity in elderly myeloma patients. ​
12. The 3-year OS was 84% in fit, 76% in intermediate-fitness, and 57% in frail patients. ​​
13. The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness, and 34.0% in frail patients. ​
14. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness, and 31.2% in frail patients. ​​
15. The International Myeloma Working Group proposes this frailty score for the measurement of frailty in designing future clinical trials. ​
16. The study included 869 newly diagnosed MM patients with a median age of 74 years. ​
17. 46% of the patients were older than 75 years. ​
18. The most frequent comorbidities were diabetes without organ damage, mild renal failure, cardiopulmonary disease, and peripheral vascular disease. ​
19. Abnormal parameters in ADL included independence in bathing, transferring, and dressing. ​
20. Abnormal parameters in IADL included mode of transportation, housekeeping, shopping, and laundry. ​
21. Advanced age, functional decline in ADL and IADL, and the presence of comorbidities were associated with a reduced overall survival (OS). ​
22. Patients aged 75 to 80 years and those older than 80 years had a higher risk of death. ​​
23. Patients with ADL score #4, IADL score #5, and CCI $2 also had a higher risk of death. ​
24. No difference was found for ADL 5, IADL 6-7, and CCI 1. ​
25. The final stratification of variables was defined as ADL (.4, #4), IADL (.5, #5), and CCI (,2, $2). ​
26. An additive frailty score was calculated based on the integer part of hazard ratios (HRs). ​
27. Patients were stratified into three risk groups for OS: fit (score 5 0), intermediate fitness (score 5 1), and frail (score $2). ​
28. Among the 260 frail patients, 123 were older than 80 years and 50 were categorized as frail only for age. ​
29. Geriatric assessment plays a crucial role in predicting survival and toxicities in elderly patients with multiple myeloma. ​
30. Comprehensive geriatric assessment (CGA) provides valuable information about the patient's functional status, comorbidities, and frailty. ​
31. Age alone should not be used as a sole determinant for treatment decisions in elderly myeloma patients. ​
32. A multidimensional approach that takes into account the patient's overall health and individualized goals of care should be employed.
33. Novel therapies have shown improved survival outcomes in elderly myeloma patients. ​
34. Further research is needed to better understand the impact of novel therapies on survival outcomes in this population. ​
35. The report highlights the importance of personalized treatment approaches for elderly myeloma patients. ​
36. The authors emphasize the need for collaboration between hematologists and geriatricians in the management of elderly myeloma patients. ​
37. The report calls for the inclusion of elderly patients in clinical trials to improve the evidence base for treatment decisions in this population. ​
38. The authors stress the importance of supportive care measures in improving outcomes and quality of life for elderly myeloma patients. ​
39. The report acknowledges the challenges in conducting clinical trials in elderly patients and calls for the development of specific trial designs for this population. ​
40. The authors highlight the need for education and awareness among healthcare professionals regarding the unique needs and challenges faced by elderly myeloma patients.
41. The report emphasizes the importance of a multidisciplinary approach in the management of elderly myeloma patients, involving hematologists, geriatricians, and other healthcare professionals. ​
42. The authors conclude that geriatric assessment should be an integral part of the evaluation and treatment of elderly myeloma patients to optimize outcomes and minimize toxicities. ​
43. The study found that the frailty score was associated with an increased risk of death, disease progression, nonhematologic adverse events (AEs), and treatment ​

Authors:

Antonio Palumbo, Sara Bringhen, Maria-Victoria Mateos, Alessandra Larocca, Thierry Facon, Shaji K. Kumar, Massimo Offidani, Philip McCarthy, Andrea Evangelista, Sagar Lonial, Sonja Zweegman, Pellegrino Musto, Evangelos Terpos, Andrew Belch, Roman Hajek, Heinz Ludwig, A. Keith Stewart, Philippe Moreau, Kenneth Anderson, Herman Einsele, Brian G.M. Durie, Meletios A. Dimopoulos, Ola Landgren, Jesus F. San Miguel, Paul Richardson, Pieter Sonneveld, and S. Vincent Rajkumar

Citation:

Blood (2015) 125 (13): 2068–2074.
https://doi.org/10.1182/blood-2014-12-615187 (https://doi.org/10.1182/blood-2014-12-615187)