Vulnerability Variables Among Octogenarians Myeloma Patients: A Single-Center Analysis in 110 Patients

In the era of an aging population an increasing number of patients are diagnosed with multiple myeloma (MM) at an age of ≥80 years. The frailty of the octogenarian population as a result of coexisting comorbidities and age-related organ impairment is an additional management challenge and often excludes this population from enrollment in clinical trials. The aim of our study was to analyze the disease characteristics, frailty scores at diagnosis and treatment toxicity profile in relation to patient outcomes. All newly diagnosed symptomatic MM patients ≥80 years of age who received at least one dose of treatment were included in the study.

Among 827 consecutive, newly diagnosed, symptomatic MM patients who were treated in the Department of Clinical Therapeutics (Athens, Greece) after 01/01/2000, 110 were ≥80 years old (13.3%); their median age at diagnosis was 83 years (range 80-92 years) and 55% were male. Performance status (PS) was 1-2 in 40% and 3-4 in 60% of the patients respectively. Anemia (Hb <10 g/dl) was present in 64.5% of patients, increased serum LDH (>250 IU/L) in 12%, hypercalcemia (calcium ≥11 mg/dL) in 19% and osteolytic bone lesions in 73% of patients. Serum creatinine was ≥2 mg/dl in 30% and eGFR (per CKD-EPI equation) was <60 ml/min/1.73m² in 69% and in 36% of patients was <30 ml/min/1.73m². Per ISS, 56% had stage-3, 35% had -2 and 9% had disease stage-1, respectively. Cytogenetics were available for 66 patients and high-risk cytogenetics were present in 9 (12%) patients.

First line treatment was bortezomib-based in 30% of patients, IMiD-based in 62%, while 8% received conventional chemotherapy. Overall response to first line treatment (≥PR) was 62% (sCR 9%, CR 4%, VGPR 30% and PR 57%). At the time of diagnosis 41% of patients required hospitalization due to disease related complications, while 60% were hospitalized at least once during their disease course. Low eGFR was associated with need for hospitalization at the time of diagnosis (p<0.001). Treatment emerging toxicities were common; 63% of our patients experienced at least one grade ≥3 event and 14% had grade 5 events. Grade ≥3 hematological toxicity was reported in 24% and grade ≥2 neuropathy in 23% of patients; 28% of patients experienced at least one grade ≥ 3 infectious episode during their disease course.

According to IMWG geriatric assessment, due to the age of the patients (≥80), all of them were categorized as frail. Using the G8 geriatric screening tool, 73% of patients had a score £ 11, per the CIRS-G scale 52% had score >17, and the Charlson Comorbidity Index was ≥2 in 49%; on the IADL scale 42% had a score £5 and on the ADL scale 18% scored £4 while the VES-13 score was ≥6 in 58% of patients.

Median survival was 21 months (95% CI 9-33 months) and early mortality (at 2 months from treatment initiation) was 20%. Several factors were associated with inferior survival in univariate analysis, including female gender (p=0.042), ISS stage-3 (p=0.015), LDH ≥250 IU/L (p=0.001) and eGFR <30 ml/min/1.73m² (p<0.001) at the time of diagnosis, while, the presence of anemia, hypercalcemia, high risk cytogenetics, and the use of bortezomib vs IMiDs-based therapy were not. Factors such as the need for hospitalization at the time of diagnosis (p<0.001) and the presence of grade 3 or 4 adverse events during the disease course (p=0.003) had a negative impact on survival. A higher score on the G8-screening tool (p=0.002) and VES13 (p=0.008) were also associated to shorter OS. However, VES13 was available only in 38 patients. In the multivariate analysis, eGFR <30 ml/min/1.73m² (p=0.003) and LDH ≥250 IU/L (p=0.048) were independently associated with poor OS, while there was a trend for a significant association for the G8 geriatric screening tool (p=0.08) and need for hospitalization at the time of diagnosis (p=0.065).

In conclusion, the octogenarian MM patient population is a distinct frail subset of MM patients and its management should be individualized considering both disease characteristics and functional status. Renal impairment at diagnosis and high LDH correlated independently with OS in this group of patients. The G8 and VES13 geriatric assessment tools can provide additional information. The need for hospitalization at diagnosis is an ominous sign. This vulnerable patient population needs detailed assessment, individualized treatment and intensive supportive care to avoid hospitalization due to complications and to reduce early mortality.