Predictors of Relapse after Definitive Treatment of Solitary Plasmacytoma: A Systematic Review

Introduction

Solitary plasmacytoma refers to a rare form of mature B-cell malignancy that can present either extraosseous i.e., solitary extramedullary plasmacytoma (SEP), or the more common type, intraosseous i.e., solitary bone plasmacytoma (SBP). According to the National Comprehensive Care Network, the primary treatment of solitary plasmacytoma is radiotherapy with 40-50 Gy to the involved field +/- surgery (if the patient is unstable or has symptoms indicative of neurological compression), or chemotherapy (if the patient has bulky disease defined as ≥5 cm or unresponsive to radiotherapy). This systematic review aimed to assess relapse predictors of solitary plasmacytoma following definitive treatment.

Methods

A systematic review was conducted in adherence to the PRISMA guidelines with a pre-specified study protocol registered on PROSPERO (CRD42023432422). A literature search was performed utilizing Medline, ScienceDirect, Google Scholar, Cochrane, and Clinicaltrials.gov, on April 15, 2023. The MeSH terms “plasmacytoma”, “recurrence”, “relapse”, “prognosis”, and “treatment” were used. The inclusion criteria were defined as retrospective, randomized, or non-randomized controlled studies published in English that include patients with solitary plasmacytomas of any site, who received radiotherapy, chemotherapy, and/or surgery, and have outcomes of overall survival, progression-free/relapsed-free survival (PFS/RFS), and time to progression to multiple myeloma.

Results

After meeting the inclusion criteria, twenty-seven studies were included. Among 1412 patients,1034 (73%) SBP, 427 (30%) SEP, and 844 (60%) males were studied. Most articles were published in the USA (15%), followed by Italy (11%) and France (11%). Several overlapping predictors of relapse were observed (Table 1), with younger age (age <60) and tumor size <5 cm the most common significant better prognostic factors; mentioned in 10 (37%) and 7 (26%) studies, respectively. Interestingly, SBP tumor type was associated with worse prognosis in 3 (11%) studies, while SEP tumor type had mixed prognostic association; worse prognostic association in 4 (15%), and better in 3 (11%) studies. Less common negative prognostic indicators included immunoparesis at diagnosis, occult marrow disease, positive serum M protein, persistent M spike, positive serum B2 microglobulin, positive Bence Jones protein, and positive urinary monoclonal light chains. Radiotherapy exhibited a better prognosis alone, with surgery, and with chemotherapy. In addition, a higher radiation dose (>40 Gy) was associated with better prognosis, supported by another study that showed a worse prognosis with a lower radiation dose (<50 Gy). Four studies did not demonstrate a statistically significant prognostic factor.

Conclusion

Tumor size and age appear to be the most common significant prognostic indicators for solitary plasmacytoma when indexed to outcomes of OS, PFS, MMFS, and median time to MM progression. Several other prognostic indicators have been reported but require further research to ascertain their strength of association and possibly direct future screening and management.