Characteristics, Outcome, and Prognostic Factors for Survival and Progression to Multiple Myeloma of Solitary Plasmacytomas: A 30-Year Experience of the Greek Myeloma Study Group

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extraosseous tumors composed of malignant plasma cells without evidence of systemic Multiple Myeloma (MM). Radiotherapy (RT) +/- surgical excision (SE) is the treatment of choice, while additional systemic therapy (ST) has not been proven beneficial. Proposed risk factors for survival and progression to MM vary across studies, many of which have relatively short follow up and include patients diagnosed primarily before 2014. Our study aimed to examine outcomes and prognostic factors for survival and progression to MM in a large cohort of SP patients diagnosed over 30 years, and to assess the impact of various therapies applied in different timepoints.

We analyzed 172 consecutive patients (pts), 115 with Solitary Bone Plasmacytoma (SBP) and 57 with Solitary Extramedullary Plasmacytoma (SEP). Male: female ratio was 84:88; median age was 62 years (17-85); 66% of cases were classified as SP and 34% as SP with minimal bone marrow involvement (i.e. <10% BM infiltration). Monoclonal paraprotein (MP) was detected in 98 pts (57%). Patients were distributed across 3 periods: 1994-2004 (31 pts), 2005-2014 (79 pts) and 2015-2024 (61 pts). Baseline characteristics of pts with SBP and SEP were compared with standard methods. Prognostic factors for overall survival (OS), progression-free survival (PFS), and MM-free survival (MMFS) were determined by Cox regression.

Characteristics including age, gender, performance status, hematology and biochemistry were similar between SBP and SEP pts; MP was more common in SΒP pts (67% vs. 37%; p<0.001); 25% of pts underwent PET CT; median SUV was 5.2, (range 3.7-41.8), similar between groups. The median size of plasmacytomas was larger in SBP pts compared to SEP pts (5.7 cm vs. 4 cm; p<0.05); SEP was most frequently located in the upper respiratory tract (63%), while SBP was more often found in the vertebrae (44%). Therapies included RT alone (78 pts), RT + ST (38 pts), RT+ SE (13 pts), ST (17 pts), SE (12 pts), ST+ SE (4 pts), RT+SE+ST (10 pts). RT was more commonly used in SBP vs. SEP (88% vs. 63%; p<0.001). Median RT dose was 40 cGy (20-60 cGy); ST was administered in 69/172 pts most of whom (71%) received novel agent combinations. Overall response and complete response (CR) were 94% and 53% respectively, similar between SBP and SEP. Median time to response was 4 months; 70 pts relapsed with most (77%) experiencing progression to MM with or without new plasmacytomas. Progression to MM was more frequent in SBP than SEP (37% vs. 23%; p=0.06). After a median follow up of 114 months (95% CI: 79-149), 109 pts were alive, 54 had died (21 from MM progression) and 12 pts were lost to follow-up. Median OS, 5- and 10-year OS were 224 months, 85% and 69% respectively, similar in both groups; median PFS, and 5- and 10-year PFS were 72 months, 54% and 40% respectively, and it was longer in SEP pts compared to SBP (132 vs. 63 months; p=0.09). Median MMFS was 121 months for SBP and not reached for SEP (p=0.09); 5- and 10-year MMFS for SBP vs. SEP was 65% vs. 75% and 52% vs. 66%, respectively. Age >60 and progression to MM were negative predictors for OS with age >60 maintaining its’ significance in the multivariate analysis (HR:3.1; p<0.001); CR (i.e. disappearance of SP and MP, if present) was the only significant positive predictor for PFS (HR: 0.51; 0.003). An abnormal baseline free light chain ratio (FLCR) was a negative predictor for progression to MM (HR: 3.5; p=0.03); RT +/- SE significantly reduced the risk for progression to MM (HR: 0.25; p=0.02). Adjuvant ST and period of diagnosis did not impact survival parameters.

Our study, one of the largest multicenter studies on pts with SP, and having the longest reported median follow-up to date showed that, pts with SP continue to experience prolonged OS which strongly correlates with patients' age rather than the type or clinical course of SP. Even though PFS was longer in pts with SEP compared to pts with SBP, achieving a CR was a stronger predictor of PFS than the type of SP. An abnormal FLCR was the only significant negative predictor for MMFS, increasing the risk of progression to MM by 3.5 times; RT +/- SE resulted in a 75% reduction in the risk for progression to MM confirming that it remains the treatment of choice for SP. Despite advances in systemic MM treatments, combined therapies do not seem to provide additional survival benefit or reduce the likelihood of SP recurrence or progression to MM.