Background: Older adults with multiple myeloma (MM) may be at increased risk for toxicity of therapy. The International Myeloma Working Group (IMWG) frailty model, which includes age, functional status, and comorbidities, accounts for the presence of toxicity. The Cancer and Aging Research Group (CARG) Toxicity Tool (Hurria et al, JCO, 2011) includes more aging-associated domains and has been well validated in older adults with solid tumors, though not in hematologic malignancies. The association between the CARG toxicity tool and toxicity of therapy in older adults with MM is unknown. The parent study tested feasibility of an electronic modified geriatric assessment (mGA) tool providing real-time results to physicians.
Methods: A retrospective chart abstraction was conducted on patients from the parent study to identify all treatments prior to the GA, time on treatment after enrollment, clinical data, treatment sequencing, incidence of Grade 3-5 toxicities, dose modifications, and treatment discontinuation or new line of therapy initiated. Patients were categorized as fit, intermediate fit or frail based on the IMWG score. The CARG score, adapted to apply to MM by removal of solid tumor type and use of the Modification of Diet in Renal Disease (MDRD) equation to calculate creatinine clearance, as recommended by the International Myeloma Working Group was calculated for each patient.
Results: Data was available on 100 patients from the parent study. Average age was 71.3 ± 5.4 years, 58% Male, and 75% White. 71 individual regimens were identified with 575 incidences of use. Most patients were on their 4th line of therapy (mean=3.8 ± 2.9) and 22 were not receiving treatment at the time of the GA. Patients averaged 4.5 ± 3.7 lines of therapy and 46 patients underwent autologous stem cell transplants. Mean time on treatment for 78 patients after mGA was 27.2 weeks ± 28.4 weeks. CARG scores ranged from 0 to 17 with a mean of 5.9 + 7.8. mGA results were 35.7% (n=35) fit, 39.8% (n=39) intermediate fit, and 24.5% (n=24) frail using the IMWG frailty score. There was significant correlation between mean CARG scores and fit/frailty status (p<.000), with higher scores in frail patients. Hematological events after GA were common with 97% (n=97) reporting 1 or more > grade 3 events. Non hematologic events were less common with 38% (n=38) reporting 1 or more > grade 3 events. Incidences of hematologic and non-hematologic toxicities were not associated with CARG or IMWG frailty status. 44.9% (44 of 98) had dose modifications and 50% (49 of 98) had early therapy cessation.
Conclusion: Older adults with MM are likely to require multiple lines of therapy over the course of their disease. Individualizing treatment and mitigating risk requires consistent application of geriatric assessment and toxicity tools. Our study did not find a significant association between the CARG toxicity tool, adapted for myeloma, or the IMWG frailty status. Future study will be needed to understand which patients were treated with initial dose reductions and how this impacted the risk of adverse events.
Disclosures
Wildes: Janssen: Research Funding; Carevive: Consultancy.
Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group
