Impact Of Initial FGD-PET CT and Serum Free Light Chain On Transformation Of Solitary Plasmacytoma To MM
Authors: Fouquet Guillemette , Guidez Stéphanie , Herbaux Charles , de Wyngaert Zoé Van , Bonnet Sarah , Beauvais David , Demarquette Helene , Hivert Bénédicte , Wemeau Mathieu , Terriou Louis , Coiteux Valérie , Macro Margaret , Decaux Olivier , Facon Thierry , Huglo Damien , Leleu Xavier 
Published: October 2019

Abstract

Background
Solitary plasmacytoma (SP) is characterized by a localized proliferation of monoclonal plasma cells resulting in a mass in either bone (SBP: Solitary Bone Plasmacytoma) or soft tissue (EMP: Extra-Medullary Plasmacytoma), without evidence of Multiple Myeloma (MM). The prognosis of SP is marked by a high risk of transformation to MM. SBP (as compared to EMP), older age, tumor size > 5 cm, and persistence of monoclonal immunoglobulin after treatment were prognostic for progression to MM. More recently, studies demonstrated that presence of focal lesions on magnetic resonance imaging (MRI) favored progression to MM in patients (pts) with plasmacytoma. The exact role of FGD-PET CT (PET) in MM remains debatable, although it clearly provides additional valuable information to assess plasmacytoma in the context of MM, compared with MRI. The prognostic role of PET in identifying progression to MM of SP has not been formally demonstrated.
We aimed to determine the impact of PET pre and post therapy on the risk of transformation of SP to overt MM.

Method
We retrospectively reviewed the medical records of 43 pts diagnosed with one SP clinically, confirmed with histology, either EMP (10 pts) or SBP (33 pts). All pts had one SP clinically, and were treated locally with surgery and/or radiotherapy. PET and MRI were performed at diagnosis prior to (initial) and at the end of therapy. SP was diagnosed as outlined in international consensus criteria. All pts had complete follow up records pre and post therapy.

Results
The median age was 57.5 years with 33% pts older than 65, the sex ratio was 1.8, IgG kappa was the most frequent isotype, the maximum M-spike value was 30g/L, 48% pts had abnormal involved serum free light chain (isFLC) value and 64% had abnormal sFLC ratio (K/L). 33% had 2 hypermetabolic lesions on initial PET, and 20% had 2 focal lesions on initial MRI. Out of the SBP, 56% were localized on spine or pelvis.
With a median follow-up of 50 months (mo), the median overall survival (OS) was not reached for the whole cohort, with a 6-year OS at 79.4%. The median time to MM progression (TTMM) was 71 mo (95%CI: 59;101). The TTMM was not significantly different in SBP versus (vs) EMP although the 5-year TTMM was 58% and 83%, respectively. The TTMM for the 2 hypermetabolic lesions on initial PET group was 23 mo (9;37) vs not reached otherwise (p=0.003). Conversely, MRI at diagnosis did not have any impact on TTMM in our study, although the median TTMM for the 2 focal lesions on initial MRI group was 30 mo (9;51) vs not reached otherwise. Age had no impact on TTMM, but abnormal initial K/L ratio (p=0.022) and abnormal initial isFLC (p=0.002) did impact TTMM, 36 mo (14;58) and 21 mo (0;42) vs not reached otherwise, respectively. A normalized PET at completion of treatment did not reach significance, as to normalized MRI, but the absence of normalized isFLC value also impacted TTMM, 21 mo (10;32) vs not reached otherwise (p=0.016). Using multivariate analysis, independent variables that impacted TTMM were abnormal initial isFLC (OR=10, 95%CI=1-87; p=0.008) and initial PET (OR=5, 95%CI=0-9; p=0.032).
Interestingly, initial PET did not influenced OS, median 71 mo for the 2 hypermetabolic lesions on initial PET group vs not reached otherwise, respectively (p=ns). This data suggested that pts with SP that transformed into MM did not have a worse prognostic at time of MM. The median OS of pts with SP from start of MM was not reached, the 4-year OS was 66%.
With a special focus on SBP, we identified the exact same prognostic factors for TTMM as to the whole cohort in univariate and multivariate analysis. The localization of SBP in the spine is usually considered of poor prognosis, but we did not find any confirmation of this observation in our study.

Conclusion
FDG-PET CT and involved sFLC value at diagnosis of SP are important predictors of the risk of progression to MM. This data analysis may lead to a different management of SP for patients with one or the 2 abnormal indicators, irrespective to the solitary clinical aspect of SP. One may consider to embrace treatment of MM for SP when FDG-PET CT and involved sFLC value are abnormal at diagnosis, while surgery and/or radiotherapy would remain the appropriate therapeutic procedure for SP otherwise.

Disclosures:
Facon: JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Leleu:JANSSEN: Honoraria; CELGENE: Honoraria.