Characteristics and Clinical Course of Myeloma in Patients 40 Years of Age or Younger: A Study of the Greek Myeloma Study Group
Authors: Symeonidis Argiris , Kastritis Efstathios , Sioni Anastasia , Delimpasi Sosana , Katodritou Eirini , Michalis Eurydiki , Repousis Panagiotis , Kartasis Zafiris , Viniou Nora-Athina , Zervas Konstantinos , Terpos Evangelos , Dimopoulos Meletios Athanasios 
Published: October 2019

Abstract
Abstract 5085
Multiple myeloma is a disease of the elderly, with a median age at diagnosis around 65 years of age. This disease occurs uncommonly in patients ≤40 years of age and thus the reports on these patients are limited. We analyzed the database of the Greek Myeloma Study Group and among 1750 unselected consecutive patients we identified 66 patients (3.7%) ≤40 years of age. Most of these young patients were males (67%), 80% had osteolytic bone disease at initial diagnosis, 49% had an ECOG performance status ≥2, 34% presented with anemia (hemoglobin less than 10 gr/dl), 10% with low platelet counts (≤130×109/L) and 14% had serum creatinine ≥2 mg/dl. When compared to patients older than 40 years, younger patients with symptomatic MM were more often males (67% vs. 55%, p=0.071), had less often renal impairment (eGFR < 60 ml/min; 22% vs. 49%, p<0.001), low serum albumin (< 3.5 gr/dl; 24% vs. 40%, p=0.013) and less often beta2-microglobulin ≥3.5 mg/dl (40% vs. 60%, p=0.013). Thus, there was a different disposition within ISS: 51% of young patients ≤40 years of age were ISS-1, 25% were ISS-2 and 25% ISS-3 compared to patients older than 40 years of age (27%, 35% and 37% for ISS-1, ISS-2 and ISS-3, respectively, p<0.001). IgD myeloma was more common in patients 40 years or younger than older patients (8% vs. 1.2%, p<0.001). Elevated serum LDH ≥300 IU/L was more common in patients ≤40 years that older patients (19% vs. 11%, p=0.061). There were no significant differences regarding performance status, the frequency of osteolytic bone disease, the frequency of anemia or low platelet counts or the degree of Bence Jones proteinuria when compared to older patients.
Most patients ≤ 40 years of age received first line therapy based on conventional chemotherapy (82%) and 18% received novel agent based therapies – there was no significant difference in the treatment type when compared to patients older than 40 years. A response to first line therapy was achieved in 52% of younger patients compared to 63% for patients older than 40 years (p=0.093).
The median survival for patients ≤40 years of age was 75 months, while for patients >40 years but ≤65 years was 50 months and for patients >65 years was 35 months (p<0.001). The survival for patients ≤40 years who started treatment before 1/1/2000 (i.e. before novel agents became available in Greece) was 60 months compared to 36.5 months for patients older than 40 years (p=0.003), while for patients who started treatment after 1/1/2000 (i.e. in the era of novel agents) the median survival for those ≤40 years has not been reached and is 49 months for patients >40 years (p=0.003).
We then evaluated several factors which could be associated with survival within the cohort of patients ≤40 years: ECOG performance status ≥2 (66 vs. 154 months, p=0.03), low platelet counts <130×109/L (69 months vs. not reached, p<0.001), advanced ISS stage (154 vs. 69 vs. 33 months for ISS-1, ISS-2 and ISS-3, respectively, p=0.048) and LDH ≥300 IU/L (21 vs. 116 months, p<0.001) were associated with inferior survival. In multivariate analysis, ECOG performance status ≥2 (HR: 3.9, 95% CI 1.43–10.5, p=0.008) and elevated LDH ≥300 IU/L (HR: 6.230, 95% CI 1.72–22.5, p=0.005) were independently associated with inferior survival in patients ≤40 years of age.
In conclusion, 3.7% of our myeloma patients were ≤40 years of age; these patients tend to be males, have more often IgD myeloma and ISS-1 disease. The median survival of these patients exceeds 6 years, and there is also a significant improvement after the introduction of novel agents with an expected survival of 10 years. Factors associated with tumor burden such as ISS-stage, low platelet counts and elevated LDH are associated with inferior survival in these young patients. Although there has been significant progress over the last decade, especially with the introduction of novel agents, efforts to further improve their outcome should be continued and perhaps cure should be the ultimate goal for as many as possible of these young patients.

Disclosures:
No relevant conflicts of interest to declare.