Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. At least 50% of all MM patients are older than 70 years of age and 20% are older than 80 years of age (Siegel R, Naishadham D, Jemal A. CA Cancer J Clin. 2012 Jan-Feb;62(1):10–29). The approach to treatment of patients with MM depends on a multitude of factors including age, underlying comorbidities, and disease characteristics. Elderly patients are under-represented in clinical trials. The purpose of our study was to assess the overall outcomes and impact of novel agents in the treatment of newly diagnosed elderly (≥75 years of age) patients with MM in a community setting.
We conducted a retrospective review of the records of MM patients seen at Rochester General Hospital, Rochester, NY, who were 75 years of age or older at the time of diagnosis of MM. The study period was from January 2001 to August 2012. Sixty-six patients met the study criteria. Patients with smoldering MM were excluded. Demographic information, comorbid conditions, disease characteristics, laboratory data, first line treatment given, response to treatment, and disease- and treatment-related complications were collected from medical records. Data were analyzed using SPSS software version 14. Univariate analysis was performed and the mean, median, and standard deviation were calculated. A statistically significant difference between variables was denoted by a p value < 0.05. Response to treatment was calculated using Bladé Criteria. Overall survival was estimated by using Kaplan-Meier curves. Grade III and IV toxicity was determined according to Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 4.0.
Sixty-six patients (median age 81 years, range 75–95 years) with symptomatic MM were studied. Sixty-two percent were males. Twenty-seven percent had underlying diabetes mellitus, 29% had experienced a prior stroke or MI, and 68% had hypertension. Charlson Co-morbidity Index (CCI) was high (3–4) in 46% and very high (≥5) in 31%. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was ≥3 in 27% of patients. Sixty-five percent of patients had IgG subtype, while 28% had IgA subtype. There was a predominance of kappa light chains over lambda (55% versus 42%). Twenty percent, 34%, and 40% of patients had International Staging System (ISS) stages 1, 2, and 3, respectively, while in 6% ISS could not be determined. The median hemoglobin level was 10.5 g/dL (range 6.1–14.8 g/dL), the median serum creatinine level was 1.3 mg/dL (range 0.1–8.0 mg/dL), the median serum albumin level was 3.2 g/dL (range 1.4–4.8 g/dL), and the median serum calcium level was 8.7 mg/dL (range 8.0–17.3 g/dL). As first line treatment 75% received standard therapy, while 25% received novel agents. The most commonly used standard therapies were cyclophosphamide + steroid (36%), melphalan + steroid (25%), and steroid alone (8%). First line therapy included bortezomib in 12%, thalidomide in 10%, and lenalidomide in 3% of patients. Median duration of first line treatment was 26 weeks (range 3–103 weeks). The median overall survival was 72 weeks (range 10–406 weeks). In those who received a novel agent as first line therapy the median overall survival was 127 weeks (range 38–318 weeks). Overall response rate (≥ partial response) was 55% in patients treated with a novel agent versus 23.6% in patients treated with standard therapy. There was no significant correlation between grade III/IV toxicity and the use of a novel agent (p=0.68). When including all non-transplant patients (> 65 years of age), there was a positive correlation between the use of a novel agent and overall survival at one year (Correlation coefficient, CC 0.281, p=0.01). The CC for elderly patients (≥ 75 years of age) was 0.175. The CC in 65–74 year-olds was 0.387. Percentage survival at one year was 59.6 % in patients ≥75 years of age versus 70.6% in those aged 65–74 years.
In conclusion, our study shows that very elderly patients (≥75 years of age) with MM, who are considerably ill at baseline with a high or very high CCI and poor PS continue to experience shortened survival despite the use of new agents. However, notwithstanding this, the early use of novel agents has a positive impact on survival at one year, with improved response rates to new therapies, and without an increase in toxicity.
Patel:Millennium Pharmaceuticals, Inc: Speakers Bureau; Eli Lilly and Company: Speakers Bureau.
Asterisk with author names denotes non-ASH members.