Contributions
Abstract: EP949
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Extramedullary disease (EMD) is a clinical manifestation of multiple myeloma (MM), characterized by a plasma cell (PC) proliferation outside of the bone marrow (BM). The expression modulation of adhesion molecules, including CD44 and CD56, involved in BM homing, supports clonal PCs migration through the bloodstream. CD38 is a multifunctional transmembrane glycoprotein, expressed by PCs, which also plays a role as adhesion molecule. CD38 is considered a hallmark of MM cells and a therapeutic target for anti-CD38 antibody-based approach, however, CD38 expression profile by extramedullary PCs is still unknown.
Aims
To analyze the clinical and cytogenetic features of EMD patients (pts) with a comparative analysis of phenotypic differences, including CD56, CD44 and CD38 between BM PCs and EMD PCs in order to disclose antigenic changes related to the EMD onset.
Methods
We investigated 22 pts (median age 67 years, range 47 – 76), affected by MM (n°20) and primary PC leukemia (n°2) with a biopsy-proven soft tissue EMD. Clinical data included the type of disease, age at the time of diagnosis and at the time of EMD, myeloma type, ISS stage, cytogenetic abnormalities. The immunostaining from BM and EMD biopsies were scored using a semiquantitative evaluation of the percentage of CD56, CD44 and CD38, on MM cells on a 5-tiered scale (score 0, < 5% positive tumor cells; score 1, 5% to 24% positive tumor cells; score 2, 25% to 49% positive tumor cells; score 3, 50% to 75% positive tumor cells; score 4, > 75% positive tumor cells).
Results
Three pts presented EMD at diagnosis while 19 pts presented EMD at relapse. The median time to EMD appearance during the relapse phase was 29 months (range 9-201 months). The most frequent MM subtype was light chain MM (41%) followed by IgG and IgA. 35% of the pts presented a high stage (ISS III) and a median LDH value above the normal limit. Overall 15 of 18 (88%) pts with available FISH, showed two or more cytogenetic alterations suggesting a high clonal heterogeneity. The most frequent cytogenetic aberration reported was amp(1q21) (72%), followed by del(13q) (65%), del(1p32) (47%), and hyperdiploidy (24%). Overall, 12 of 22 (55%) pts with EMD developed multiple plasmacytomas. The most common site was soft tissue (muscle, subcutaneous fat) and liver/spleen which represents 42%, of the total EMD followed by lymph nodes (15%). In 41% of the pts, the EMD relapse was dissociated from BM relapse that showed polyclonal plasmacytosis. CD56 showed a high score (3-4) in 5 of 22 (23%) EMD samples and was absent in 14 of 22 (64%) pts. 3 out 13 patients with discordant CD56 expression (18%) showed a strong down-regulation of CD56 in the EMD samples compared to BM. CD44 showed a high score (3-4) in 16 of 20 (80%) EMD samples and was absent in 2 of 20 (10%). Four pts with discordant CD44 expression (27%) showed an up-regulation of CD44 in the EMD samples compared to BM. CD38 had a high immunohistochemical score (3-4) in 16 of 19 BM samples (84%) and in two pts was negative. CD38 was absent (score 0) in 3 of 22 (14%) EMD samples and showed a low score (1-2) in 4 of 22 (16%) patients. Discordant CD38 expression was observed in 26% of samples with a down-regulation of CD38 in the EMD samples compared to BM.
Conclusion
Our data indicate that discordant expression of CD56, CD44 and CD38 may occur in EMD lesions compared to BM. The possible lack of CD38 expression in EMD was highlighted for the first time and it should be considered for its therapeutic impact.
Keyword(s): CD38, Myeloma
Abstract: EP949
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Extramedullary disease (EMD) is a clinical manifestation of multiple myeloma (MM), characterized by a plasma cell (PC) proliferation outside of the bone marrow (BM). The expression modulation of adhesion molecules, including CD44 and CD56, involved in BM homing, supports clonal PCs migration through the bloodstream. CD38 is a multifunctional transmembrane glycoprotein, expressed by PCs, which also plays a role as adhesion molecule. CD38 is considered a hallmark of MM cells and a therapeutic target for anti-CD38 antibody-based approach, however, CD38 expression profile by extramedullary PCs is still unknown.
Aims
To analyze the clinical and cytogenetic features of EMD patients (pts) with a comparative analysis of phenotypic differences, including CD56, CD44 and CD38 between BM PCs and EMD PCs in order to disclose antigenic changes related to the EMD onset.
Methods
We investigated 22 pts (median age 67 years, range 47 – 76), affected by MM (n°20) and primary PC leukemia (n°2) with a biopsy-proven soft tissue EMD. Clinical data included the type of disease, age at the time of diagnosis and at the time of EMD, myeloma type, ISS stage, cytogenetic abnormalities. The immunostaining from BM and EMD biopsies were scored using a semiquantitative evaluation of the percentage of CD56, CD44 and CD38, on MM cells on a 5-tiered scale (score 0, < 5% positive tumor cells; score 1, 5% to 24% positive tumor cells; score 2, 25% to 49% positive tumor cells; score 3, 50% to 75% positive tumor cells; score 4, > 75% positive tumor cells).
Results
Three pts presented EMD at diagnosis while 19 pts presented EMD at relapse. The median time to EMD appearance during the relapse phase was 29 months (range 9-201 months). The most frequent MM subtype was light chain MM (41%) followed by IgG and IgA. 35% of the pts presented a high stage (ISS III) and a median LDH value above the normal limit. Overall 15 of 18 (88%) pts with available FISH, showed two or more cytogenetic alterations suggesting a high clonal heterogeneity. The most frequent cytogenetic aberration reported was amp(1q21) (72%), followed by del(13q) (65%), del(1p32) (47%), and hyperdiploidy (24%). Overall, 12 of 22 (55%) pts with EMD developed multiple plasmacytomas. The most common site was soft tissue (muscle, subcutaneous fat) and liver/spleen which represents 42%, of the total EMD followed by lymph nodes (15%). In 41% of the pts, the EMD relapse was dissociated from BM relapse that showed polyclonal plasmacytosis. CD56 showed a high score (3-4) in 5 of 22 (23%) EMD samples and was absent in 14 of 22 (64%) pts. 3 out 13 patients with discordant CD56 expression (18%) showed a strong down-regulation of CD56 in the EMD samples compared to BM. CD44 showed a high score (3-4) in 16 of 20 (80%) EMD samples and was absent in 2 of 20 (10%). Four pts with discordant CD44 expression (27%) showed an up-regulation of CD44 in the EMD samples compared to BM. CD38 had a high immunohistochemical score (3-4) in 16 of 19 BM samples (84%) and in two pts was negative. CD38 was absent (score 0) in 3 of 22 (14%) EMD samples and showed a low score (1-2) in 4 of 22 (16%) patients. Discordant CD38 expression was observed in 26% of samples with a down-regulation of CD38 in the EMD samples compared to BM.
Conclusion
Our data indicate that discordant expression of CD56, CD44 and CD38 may occur in EMD lesions compared to BM. The possible lack of CD38 expression in EMD was highlighted for the first time and it should be considered for its therapeutic impact.
Keyword(s): CD38, Myeloma