Clinical Features and Outcome of Newly Diagnosed, Symptomatic Patients with Multiple Myeloma ≥80 Years of Age: An Analysis of the Greek Myeloma Study Group
Authors: Dimopoulos Meletios Athanasios , Kastritis Efstathios , Delimpasi Sosana , Katodritou Eirini , Hatzimichael Eleftheria , Kyrtsonis Marie-Christine , Repousis Panagiotis , Tsirogianni Maria , Kartasis Zafiris , Parcharidou Agapi , Michael Michalis , Michalis Eurydiki , Gika Dimitra , Symeonidis Argiris , Terpos Evangelos , Zervas Konstantinos 
Published: October 2019

Abstract
Abstract 5084
Multiple myeloma (MM) affects mainly persons >60 years. Since the population of octogenarians steadily increases, it has become common to treat patients of ≥80 years of age. Their management is a challenge because these patients have often significant comorbidities and the treatment toxicity is a major concern. These patients are not often included in clinical trials due to poor performance status (PS), renal impairment (RI) or other comorbidities and thus there are limited data on their characteristics and treatment outcome. To address these issues we searched the database of the Greek Myeloma Study Group to identify patients with symptomatic myeloma who were ≥80 years of age at the time of initial therapy and who were treated in the novel agent era.
Among 601 consecutive patients with symptomatic, newly diagnosed, myeloma who started treatment between 1/1/2003 and 31/12/2010, we identified 110 (18%) patients of ≥80 years of age. Most patients were males (57%) and had an ECOG PS ≥2 (61.5%). Lytic bone disease was present in 78% of them, anemia (Hb<10 mg/dl) in 56%, low platelet counts (<130×109/L) in 20%, elevated serum LDH (≥300 IU/L) in 14%, while 64% had ISS-3, 30% ISS-2 and only 6% had ISS-1 MM (p=0.001). RI was common: 34% had serum creatinine ≥2 mg/dl but 63% had eGFR <60 ml/min and 31.5% had eGFR <30 ml/min. When compared to patients <80 years of age, then, patients≥80 years had more often poor PS (P=0.001), anemia (p=0.004), low platelet counts (p=0.016), elevated serum creatinine and low eGFR (p<0.001), low serum albumin (p<0.001) and elevated beta2-microglobulin (p<0.001). IgA MM was more common in patients ≥80 years of age (37% vs. 21.5%) and IgG MM was less common (47% vs. 57%, p=0.004). First line therapy was based on novel agents in 60% of these patients compared to 72% in patients <80 years (p=0.014). Response to first line therapy (PR or better) was lower in patients ≥80 years (55% vs. 74%; p<0.001). When patients who died early (<2 months) were excluded from the analysis, then response to therapy for older patients was 63%.
The median survival of patients ≥80 years was 22 months and 17 patients (15%) died within the first 2 months from the initiation of therapy. The survival was 22 months for males and 31.5 months for females (p=0.391). Patients with PS ≥2 had a median survival of 19.5 months vs. 29 months for all others (p=0.018). There were no significant differences in terms of survival of patients who presented with lytic bone disease (p=0.576), anemia (p=0.556), low platelet counts (p=0.995), or ISS stage (p=0.251). The degree of RI was not associated with shorter survival in patients ≥80 years. There was no difference regarding survival among patients with different myeloma subtypes (IgA vs. IgG vs. light chain only). Patients ≥80 years with elevated LDH≥300 IU/L had a very short survival (9.4 vs. 27.5 months, p=0.016).
There were no significant differences in the characteristic of patients who were treated with novel agents or with conventional chemotherapy (CC) for any of the baseline characteristics such as gender, PS, lytic bone disease, anemia, low platelet counts, RI or high LDH. The median survival of patients ≥80 years who were treated upfront with CC was 18 months and of those who received therapy based on novel agents was 27.5 months (p=0.494). Early death rates were 18% vs. 11% for patients treated with CC vs. novel agents. When we excluded patients who died within the first 2 months, the survival of patients who treated with novel agents was 29 months vs. 22 months for patients treated with CC (p=0.896). In a landmark analysis, that excluded patients who died early (<2 months), response to first line therapy was associated with improved survival (30 vs. 18 months, p=0.017).
In conclusion, patients with symptomatic myeloma ≥80 years of age often present with high risk features. Their median survival is <2 years and, furthermore, many patients die within 2 months after treatment initiation, usually due to infectious complications. First line therapy with novel agents is associated with higher response rates without increased early mortality and with at least a 6-month survival benefit. This patient subgroup benefits from treatment with novel agents; however, reduced doses and aggressive supportive care are needed in order to reduce early mortality and to improve safety and patients' survival.

Disclosures:
No relevant conflicts of interest to declare.