Clinical Characteristics, Chromosomal Abnormalities and Outcomes in Very Elderly Patients with Multiple Myeloma: The IFM Experience

The incidence of multiple myeloma (MM) considerably increases with age. At least half of all MM patients are older than 70 years of age and 20 to 30% are older than 80 years of age. Furthermore, the number of elderly patients with MM is likely to increase due to the increasing life-expectancy of the general population. Between 2010 and 2030 the accrual annual incidence is expected to be about 50%. Until recently no survival improvment was seen in patients over 75 years. We aimed to describe the clinical and cytogenetic characteristics of this group of patients, and define their clinical outcome.

We selected within the IFM database all patients with symptomatic MM older than 75 years of age with available clinical data, characterized for the most common chromosomal rearrangements, treated between 05/2000 and 10/2010. In terms of survival and chromosomal abnormalities a comparison was performed with 770 patients aged between 65 and 75 years issued from the IFM database during the same period of time.

651 patients older than 75 years (75 - 94) centrally analyzed for chromosomal abnormalities, the incidence were 37% for del(13), 8.3% for t(4;14) and 6.1% for del(17p). Incidence of del(13) and t(4;14) were significantly lower than for patients under 65 years (45% and 14.3% respectively) and also for patients between 65 and 75 years (43.6% and 10.9% respectively) (p 0.004 and < 0.0001, ref Avet-Loiseau H. et al, abstract ASH meeting Blood 2011 ). The incidence of del(17p) was stable among age. Treatment modalities and follow-up data were available for 335 patients. The median age was 79 years and 40% were older than 80 years. Isotypes were the following: IgG 59% of patients, IgA in 23% and light chain in 16% of the cases respectively. The median beta 2 microglobulin was 5.2 mg/l (1.6 – 54.1), 45% of patients presented with ISS 3 and 18% of patients had renal impairment at time of diagnosis (creatinine value >160 micromol/L). Frontline therapy consisted of melphalan + prednisone (MP) in 72 patients (21.5 %), MP + thalidomide in 179 patients (53 %), MP + bortezomib in 26 patients (8%), lenalidomide and dexamethasone in 52 patients (15.5 %) and 6 patients (2 %) were treated in a semi-intensive approach including autologous stem cell transplantation. Overall, the median progression free survival (PFS) was 20.5 months (CI 95% 21.1–24.8) and the median overall survival (OS) was 37.6 months (CI 95% 28–46.3). This PFS was not different as compared with patients treated in between 65 and 75 years of age (median 23 months CI 95% 21.1–24.8). Nevertheless, OS was significantly higher in this latter group of patients (median 51 months CI 95% 45.1–59.2, p < 10-4) suggesting better salvage therapies in younger patients and the impact of potential comorbidities. In patients older than 75 years of age, both t(4;14) and del(17p) adversely impact PFS and OS.

Our survival results compare very favorably with those recently reported in the same population, with OS usually inferior to 24 months (ref Ludwig H et al., J Clin Oncol, 2010;28:1599–1605). This is attributed to the routine use of novel agents thalidomide, bortezomib, and lenalidomide, as part of frontline therapy, but also at the time of relapse. Treatment strategies should be specifically tailored to very elderly patients to optimize tolerability and efficacy.

Hulin:janssen: Honoraria; celgene: Honoraria. Off Label Use: carfilzomib as part of frontline therapy in myeloma. Roussel:celgene: Honoraria; janssen: Honoraria. Kolb:janssen: Honoraria; celgene: Honoraria.