[1368] Immunophenotypic Profiles of Plasma Cells in Myeloma Precursor Disease Correlate with the Extent of Disease and Risks for Progression

Katherine R Calvo, Meghan Corrigan-Cummins, Rene Costello, Prashant Tembhare, Constance M Yuan, Maryalice Stetler-Stevenson, Neha Korde, Mary Kwok, Mary Ann Yancey, Marcia Mulquin, Olga Simakova, Zingone Adriana, Ola Landgren, Irina Maric. NIH CC, Bethesda, MD; NCI, Bethesda, MD

Background: Recent studies show that multiple myeloma (MM) is consistently preceded by a precursor state, monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM); however, we lack markers to predict progression to MM. Aberrant immunophenotypic profiles of plasma cells (PCs) in relationship to plasma cell burden and risk for progression to MM have not been investigated in a large cohort of MGUS/SMM.
Design: Total of 98 patients enrolled in the NIH prospective natural history study of myeloma precursor disease were part of this analysis. Bone marrow samples from 42 MGUS and 56 SMM diagnosed by WHO criteria were analyzed by immunohistochemistry (IHC: CD138, K, L, CD20, CD56, CD117, cyclinD1) and flow cytometry. Data was correlated with multiple clinical parameters for progression risk assessment.
Results: CD138 IHC of core biopsies revealed that estimated % of PCs was 2.3 times higher on core biopsies compared to aspirate smears. Results of the immunophenotypic analysis of core biopsies, flow cytometric and laboratory findings are presented in the table.

 0-9% PCs (N=31)10-19% PCs (N=39)≥ 20% PCs (N=28)
CD56+ cases (IHC)16%36%*64%*
CD56+ cases (Flow)29%41%*68%*
CyclinD1+ cases (IHC)6%18%*36%*
CD117+ cases (IHC)45%56%64%
Double CD56+, CyclinD1+ cases (IHC)0%3%21%*
Triple CD56+, CyclinD1+, CD117+ cases (IHC)0%3%14%*
Triple CD56-, CyclinD1-, CD117- cases (IHC)29%13%0%*
Cases with ≥ 95% clonal PCs (Flow)6%31%*79%*
Median % clonal PCs (Flow)27.2%75.8%96.3%*
M-Spike (Median)0.461.1*1.9*
Isotype IgG/non-IgG (# cases)22/929/919/4
Light chain only (# cases)015
* p< 0.05

Percent of cases with aberrant expression of CD56 and Cyclin D1 increased with increase in PC burden, while expression of CD117 did not significantly change. Strikingly, cases double positive for CD56 and CyclinD1 or triple positive for CD56, CyclinD1 and CD117 were not present in the MGUS group, and were seen mostly in patients with significant PC burden (>20% PCs). These cases were associated with significantly higher M-spikes, abnormal serum free light chain ratios, and immunoparesis. Interestingly, light-chain only disease was mostly associated with high PC burden (> 20% PCs). Conversely, cases negative for all three aberrant markers were present only in the MGUS group (<10%PCs).
Conclusions: Immunophenotypic profiles of plasma cells in myeloma precursor disease correlate with the extent of plasma cell burden and unfavorable parameters for disease progression.
Category: Hematopathology

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 230, Wednesday Afternoon


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