Clinical Features, Outcome and Prognostic Factors For Survival and Evolution To Multiple Myeloma Of Solitary Plasmacytomas: A Report Of The Greek Myeloma Study Group In 97 Patients

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary tumors consisting of monoclonal plasma cells, without evidence of systematic multiple myeloma (MM). The treatment of choice is local radiotherapy (RT) with or without surgical excision (SE). Our aim was to describe the clinical features, the outcome and prognosis of SP patients. Thus, we studied 97 consecutive patients, 65 with solitary bone plasmacytoma (SBP) and 32 with solitary extramedullary plasmacytoma (SEP), (M/F: 66/31, median age: 61 years, range 17-85 years) who were diagnosed and treated in 12 Greek Myeloma Centers; treatment was given according to each center’s local policy.

Patients with SBP and SEP did not differ in age, gender, performance status (PS), Hb, CRP, LDH, calcium, beta2-microglobulin, renal function or impairment of humoral immunity (immunoparesis). Patients with SEP presented more often with serum or urinary monoclonal component (p<0.001 and p=0.004, respectively). The median size of SP was larger in patients with SBP compared to patients with SEP (5.5cm vs. 3cm; p=0.003). CD56 antigen was expressed more often on plasma cells of SBP biopsies (p=0.03). Eighteen (56.2%) patients with SEP presented with upper respiratory track plasmacytoma and 14 presented with plasmacytomas in other locations. In 26/65 patients (40%) with SBP, plasmacytoma was located in the vertebrae and 39 had plasmacytoma in other bones. Bisphosphonates were administered more frequently in SBP patients (p=0.001). There was no difference in the type of treatment (RT, conventional chemotherapy (CT) ± novel agents (NA), SE or combined treatment) between the 2 groups; 80 patients (82.5%) received RT alone or in combination with CT and/or SE, 7 patients (7.2%) received CT alone, 7 patients (7.2%) underwent only SE and 3 patients (3.1%) were treated with CT and SE. The median dose of radiation delivered was 40 Gy (range 24-55 Gy). Novel agent combinations were administered in 27/47 patients (57.4%) who received CT (bortezomib-based regimens: 46.8%); 13/47 (27.6%) patients treated with CT underwent high-dose therapy. Myelotoxicity, neurotoxicity and neutropenic infections presented more frequently in patients treated with CT (p<0.001, p=0.01, p=0.009, respectively). Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively. There was no difference in response rates or median time to response (3 months, range 1-24 months) between patients with SBP or SEP. Overall, 38 (39.2%) patients relapsed (relapse of SP only: 14; progression to MM only: 16, relapse of SP and progression to MM: 8). After a median follow up of 60 months (range 3-264 months), 74 (76.3%) patients were alive, 13 (13.4%) were dead and 10 (10.3%) patients were lost to follow up. Overall survival (OS), although higher in SEP over SBP, did not reach statistical significance. The 10-year MM-free survival (MMFS) was 50% vs. 70% respectively, for patients with SBP vs. SEP (p=0.054). Ten-year OS for patients treated with RT± surgical excision was 81% vs. 70% for those treated with other therapies including CT± NA (p=0.3). Overall, the 10-year OS, plasmacytoma relapse-free survival (PRFS), progression-free survival (PFS) and MMFS was 78%, 58%, 43% and 59%, respectively. In the multivariate analysis PRFS and age predicted for OS (p=0.02, HR: 0.97; 95% CI: 0.94-0.99 and p=0.01, HR: 1.09; 95% CI: 1.017-1.16, respectively); 10-year OS for patients <60 vs. ≥60 years was 85% vs. 60% (p=0.02); patients with PRFS >24 vs. ≤24 months had a 10-year OS of 82% vs. 60% (p=0.01). Achievement of CR predicted positively for PRFS. Immunoparesis (n=24) predicted negatively for progression to MM. Chemotherapy including NA had no prognostic impact on OS, PRFS or MMFS.

Our study demonstrated that patients with SP enjoy a prolonged OS that is favorably influenced by young age and PRFS. We also confirmed that patients with SBP progress more frequently to MM compared to SEP in the era of novel agents. Radiotherapy with or without SE remains the treatment of choice for SP. The additional use of systematic therapy including novel anti-myeloma agents increases toxicity without improving survival or decreasing the probability of SP relapse or progression to MM. Immunoparesis predicts for progression to MM.