Page 227 - Haematologica April 2020

Fractures and survival in MM
Table 1. Characteristics of patients with multiple myeloma with and without fractures after multiple myeloma diagnosis.
Variable
Number of patients
Male/female %
Age mean
Agemedian 72 72 72
All Fracture at the same day or after MM diagnosis
14,013 3,235 (23.1%)
No fractures at the same day or after MM diagnosis
10,778 (76.9%)
54.9/45.1 45.7/54.3 70.8 70.4
57.6/42.4 70.9
Age range
Year at MM diagnosis
1990-1999
2000-2013
MM: multiple myeloma.
20-99
5,462
8,551
29-97
1,211 (22.2%)
2,024 (23.7%)
20-99
4,251 (77.8%)
6,527 (76.3%)
Figure 1. Incidence of fractures from 12 months before until ten years after multiple myeloma (MM) diagnosis in MM patients (n=14,013) and matched controls (n=53,154). For each individual, only a single fracture that occurs closest in time from MM diagnosis for the patient or the corresponding case is shown.
in 1990-1999 to 3.3 years in 2000-2013. Median time to first fracture was 1.5 years for MM patients with a fracture and 10.4 years for all MM patients (Figure 2).
Effect of fractures at diagnosis on survival and landmark analysis
A total of 1,213 (8.7%) of all MM patients were diag- nosed with a fracture at MM diagnosis (within 30 days before or after MM diagnosis). The patients with a frac- ture at diagnosis were at a significantly increased risk of death compared to those without a fracture (HR=1.28; 95%CI: 1.19-1.37). A total of 11,541 patients were alive six months after MM diagnosis and were included in the landmark analysis. Of these, 876 (7.6%) patients devel- oped a fracture during the first six months after MM diag- nosis (from the day of MM diagnosis). Patients with a fracture during the first six months after MM diagnosis were at a significantly higher risk of death compared to those with no fractures in the first six months (HR=1.31; 95%CI: 1.20-1.42) (Figure 3).
Effect of fractures on survival after multiple myeloma diag- nosis, by subtype, gender, age, and calendar period
The risk of death was significantly increased for patients who developed a fracture after the time of MM diagnosis (HR=2.00; 95%CI: 1.90-2.10) for all fractures combined. The risk of death was significantly increased in patients
who developed all subtypes of fractures after MM diagno- sis; pathologic fracture (HR=2.17; 95%CI: 2.03-2.32), ver- tebral fracture (1.74; 95%CI: 1.61-1.87), hip fracture (1.99; 95%CI: 1.82-2.18), femoral fracture (2.62; 95%CI: 2.32- 2.98), humerus fracture (2.57; 95%CI: 2.31-2.85), forearm fracture (1.24; 95%CI: 1.05-1.46), rib fracture (1.52; 95%CI: 1.31-1.77), pelvis fracture (1.99; 95%CI: 1.74- 2.29), except ankle fracture (1.07; 95%CI: 0.79-1.44) (Figure 4). The risk of death was similar for males and females with a fracture as compared to males/females without a fracture (HR=2.01; 95%CI: 1.88-2.16 and 1.99; 95%CI: 1.86-2.13, respectively). The risk of death for MM patients over 70 years old at diagnosis with a fracture compared to those without a fracture was significantly increased (HR=1.88; 95%CI: 1.77-2.00). However, in patients under 70 years old at MM diagnosis, the risk of death in patients with a fracture compared with those without a fracture was more pronounced (HR=2.28; 95%CI: 2.11-2.47). The interaction effect of fracture and age group was significant, signifying that the HR for MM patients under 70 years old at diagnosis was significantly higher than for patients ≥70 years old at diagnosis (HR=1.22; 95%CI: 1.11-1.34; P<0.01).
The risk of death for MM patients with a fracture after MM diagnosis was lower in patients diagnosed during 2000-2013 (HR=1.79; 95%CI: 1.67-1.91) compared to 1990-1999 (2.26; 95%CI: 2.10-2.42). This difference was
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