B03: SKELETAL-RELATED EVENTS AND ABNORMAL MRI PATTERN AT DIAGNOSIS ARE ASSOCIATED WITH INFERIOR OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA

Introduction: Skeletal related events (SREs) remain a devastating consequence of multiple myeloma bone disease (MMBD). The presence of osteolytic disease increases the risk of SREs, which include pathologic fractures, spinal cord compression (SCC) and need for surgery or radiotherapy to bone. Methods: In this context, we conducted this single-center, prospective, observational study to determine the incidence of SREs among MM patients who received treatment with novel agents during first-line therapy (NDMM) and explore possible correlations with disease characteristics, imaging finding and patient prognosis. Results: Overall, data from 370 patients with NDMM according to the International Myeloma Working Group criteria are included in the present analysis. 200 (54%) were males, whereas 99% were Caucasian. The median age at diagnosis was 65 (range 31-92). One third (n=120) had an ECOG performance status (PS) of 0, 27% (n=100) a PS of 1, 8% (n=30) a PS of 2 and 32% (n=120) a PS of 3-4. One third were ISS stage 1 (34%), one third were ISS stage 2 (35%) and another third were ISS stage 3 (31%). 214 patients (58%) had IgG myeloma subtype, 90 patients had IgA (24%) and 62 patients had light-chain myeloma (17%). At diagnosis, the patients were evaluated for the presence of MMBD with at least one of the following imaging modalities: whole body X-rays (WBXR), whole body low dose computed tomography (WBLDCT) and magnetic resonance imaging (MRI). Based on the WBXR, 73 patients (20%) had no osteolytic lesions, 48 patients (13%) had 1 to 3 lytic lesions and 223 patients (60%) had more than 3 lytic lesions at diagnosis. According to WBLDCT, only 12 (3%) patients had no osteolytic lesions, whereas 7 (2%) patients had 1 to 3 lytic lesions and 76 (20%) had more than 3 lytic lesions (data available for 95 patients). Based on MRI findings, 58 patients (16%) had normal MRI pattern, 151 (40%) had focal MRI pattern, 139 (38%) patients had diffuse MRI pattern and 22 (6%) had variegated MRI pattern at diagnosis. Regarding treatment regimens at first line, 161 patients received IMiD– based regimens, 152 patients received PI-based treatments, 24 patients received PI and IMiD-based regimens, whereas 33 patients received therapy based on alkylating agents. SREs were observed in 183 patients at diagnosis: 154 (154/370 42%) patients presented with pathological fractures (110 with vertebral fractures, 29 with rib fractures and 15 with fractures of the long bones; 6 patients had both vertebral and 14 long bone or rib fractures), while 11 (11/370 3%) needed radiotherapy, 9 (9/370 2%) surgery to bone and 9 (9/370 2%) patients presented with spinal cord compression. The incidence of SREs at diagnosis was higher in patients with osteolytic lesions. Among patients with SREs at Diagnosis, 92.4% showed new SREs during the disease course with WBLDCT. Among those without SREs at diagnosis, 72.2% showed new SREs with WBLDCT. Importantly, patients with normal MRI pattern, who did not present with SREs at diagnosis, had statistically significant improved median overall survival in comparison with patients who had abnormal MRI pattern or presence of SREs at diagnosis (9.2 vs 6.5 years, p=0.048). Conclusion: Approximately one half of NDMM patients presented with SREs at diagnosis. The presence of SRE or abnormal MRI pattern was associated with inferior survival. SREs lead to functional impairment and increased mortality rates; therefore early detection and prompt management is essential.