“Update” on “solitary” plasmacytoma Roger Owen St James’s Institute of Oncology, Leeds.

What are the issues? Plasmacytoma of bone - significant risk of progression - staging and risk models - early intervention? Extraosseous plasmacytoma - why is biology different and risk of progression low? - diagnostic issues - secondary soft tissue disease Plasmablastic tumours

Incidence data (HMRN)

Progression typically new site or MM Local recurrence rare Occult disease

Predicting outcome in solitary plasmacytoma of bone. Dimopoulos et al, Blood 96:2037-2044, 2000.

Urinary light chains and outcome The presence of ULC was also associated with an inferior outcome because progression was documented in 91% (10/11) with ULC and 44% (15/34) without. The median TTP was 16 vs 82 months, respectively (P < .001). Quentin A. Hill et al. Blood 2014;124:1296-1299

Impact of SFLC on progression and overall survival in solitary bone plasmacytoma. Kaplan-Meier plots for time to progression and overall survival in our cohort of patients with solitary bone plasmacytoma. For the analysis, 116 patients with available free light chain (FLC) ratios were evaluated. An abnormal FLC ratio at diagnosis had an adverse effect on both time to progression to multiple myeloma (A) and on overall survival (B). Dingli et al. Blood 2006;108:1979-1983

Mayo risk model in solitary bone plasmacytoma. Progression of solitary bone plasmacytoma. Risk of progression of solitary bone plasmacytoma to myeloma using a risk stratification model that incorporates the serum free light chain (FLC) ratio measured at baseline (A) or 1 to 2 years following diagnosis (B) and the persistence of serum monoclonal protein 1 to 2 years following diagnosis. The top curve illustrates risk of progression with time in patients with both risk factors, namely an abnormal serum free light chain ratio (< 0.26 or > 1.65) and M protein level of 5 g/L (0.5 g/dL) or more (high risk); the second gives the risk of progression in patients with any one of the 2 risk factors (intermediate risk); the third curve illustrates the risk of progression with neither risk factor present (low risk). The date at which the test for presence of serum M protein 1 to 2 years following diagnosis was determined was used as time 0 for this analysis. David Dingli et al. Blood 2006;108:1979-1983

Impact of monotypic BMPC Am J Hematol. 2012; 87(7): 647–651

Detecting occult marrow disease by flow cytometry: plasmacytoma with minimal marrow involvement. Paiva – approx. 50% neoplastic pc. Median 0.2% Hill – 68% neoplastic pcs median 0.5% Bruno Paiva et al. Blood 2014;124:1300-1303 Quentin A. Hill et al. Blood 2014;124:1296-1299

PET Imaging Am J Hematol. 2012; 87(7): 647–651

PET and SFLC Abnormal FLCr ~25% Abnormal involved LC ~50% PET >2 ~25% Guillemette Fouquet et al. Clin Cancer Res 2014;20:3254-3260

PET-negativity Study design, imaging results, and patients’ characteristics. (A) Top panel: the study design is shown. Bottom panel: the proportion of patients with specific imaging results and representative paired FDG-PET/DWIBS images. (B) Bars represent the percentage of patients positive for the respective feature. Low BMPCs were defined as ≤20%. Significance of Fisher exact test is illustrated with symbols: +P < .1; *P < .05; **P < .01; ****P < .0001. For statistical calculations, the set of DWIBS+PET+ patients was used as reference. BMPC, bone marrow plasma cell infiltration; HY, hyperdiploid; IgG, immunoglobulin G; ISS 3, International Staging System 3; LDH, lactate dehydrogenase; PR, proliferative. Leo Rasche et al. Blood 2017;130:30-34

N=28 Physicians choice Short duration of therapy

IDRIS study High-risk patients randomized to Len-Dex (9 cycles) or no further Rx following IFRT (45Gy) PFS primary endpoint BM MRD RTQA

Extraosseous disease Favourable outcome Why?

BMPC in extraosseous plasmacytoma Leeds data 18 patients assessed PC’s median 0.36% (range 0.14-2.06%) Neoplastic plasma cells detected in 10 (56%) Neoplastic PC’s median 0.3% (range 0.05-1.26%) Boll et al, BJ Haem 2010 TTP to MM according to sensitive MFC immunophenotypic evaluation of the BMPC compartment. (A-B) TTP of patients with SP grouped according to the presence vs absence of BM phenotypically aberrant clonal PCs by MFC immunophenotyping for patients with SBP and EMP, respectively. Bruno Paiva et al. Blood 2014;124:1300-1303

Diagnosis Marginal zone lymphoma main differential Absence of B-cell component “Myeloma-like” immunophenotype IGH translocations Absence of MALT1 rearrangements Boll et al, BJ Haem 2010 Parkins et al, Leuk Lymphoma 2010; 51:1360-2

Plasmablastic lymphoma Diagnostic challenge Blastic cytology and high Ki-67 CD20- CD38+ IRF4+ CD319+ CD138+/- EBV MYC Clinical correlates Dismal outcome Myeloma-like therapy?

Conclusions Progression outside field of radiation major challenge in SPB Occult marrow disease predictive of outcome and trials of adjuvant therapy warranted No biological data Extraosseous disease different biology Plasmablastic lymphoma real unmet need