- Email: [email protected]
Plasmacytomas in Multiple Myeloma: 45-Years Experience from a Single Institution
Abstracts 1
University Hospitals Birmingham NHS Foundation Trust, Birming-
ham, West Midlands; 2University of Birmingham, Birmingham, United Kingdom; 3Royal Wolverhampton Hospitals, Wolverhampton, United Kingdom
Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are characterised by the accumulation of malignant plasma cells within bone marrow and lead to a range of abnormalities in the peripheral blood T cell repertoire. We investigated the level of inflammatory chemokines within the bone marrow and blood of patients with MGUS and MM and related this to the pattern of chemokine receptor expression on T cells in both compartments. The expression of a wide range of chemokine ligands for CXCR3 and CCR4 was markedly increased within the bone marrow of patients with MGUS and MM compared to healthy donors. The most marked effects were seen for CCL4 and CXCL9 which were increased by 4 and 6 fold respectively in the bone marrow of patients with myeloma. The expression of CXCR3 and CCR4, the major TH1 and TH2-associated chemokine receptors, was increased substantially on T cells within the bone marrow of patients whereas the percentage of CXCR3-expressing T cells within blood was correspondingly decreased. The presence of even small numbers of neoplastic plasma cells can therefore generate an inflammatory chemokine tumour microenvironment. This leads to the recruitment and retention of specific T cell subsets and is likely to underlie many of the features regarding the nature of the peripheral T cell repertoire in these patients. This local inflammatory reaction may represent a tumour-specific immune response or may itself play an important role in tumour progression and as such may offers a potential novel target for therapeutic intervention.
PS-192 Plasmacytomas in Multiple Myeloma: 45-Years Experience from a Single Institution 1
2
a
Laura Rosiñol, Raquel Jiménez, M Teresa Cibeira, Carlos Fernández de Larrea,4 Esther Bladé,3 Natalia Tovar,3 Joan Blade3 1
(548 males, 568 females) were diagnosed and treated at our institution from January 1970 to December 2014. Results: Overall, 220 patients (19.7%) had Ps at diagnoses (17.1% PPs and 2.6% EMPs). The incidence of PPs in period 1 was 12.9% versus 21.6% in period 2 (p<0.0001) while the incidence of EMPs remained unchanged over the years (2.5% versus 2.6% in periods 1 and 2, respectively). The median OS of patients with PPs was 3.5 years (2.1 years in period 1 and 5.2 years in period 2) while the median OS of patients with EMPs was 1.8 years (1.3 years in period 1 and 3.9 years in period 2) being the diference in OS statistically significant between patients with PPs and EMPs (p¼0.03). The OS of patients without Ps was 3.4 years (2.6 years in period 1 and 4.8 years in period 2) which was similar to the OS of patients with PPs (p¼0.5) and significantly longer than that observed in patients with EMPs (p¼0.03). The overall incidence of Ps at relapse was 21.6% (15% PPs and 6.6% EMPs). 43% of patients with Ps at diagnoses developed Ps at first or subsequent relapses versus 14.6% of patients without Ps at diagnoses (p<0.0001). The OS from the time of relapse with Ps was significantly longer in those who relapsed with PPs compared with patients who developed EMPs (median 11.4 versus 10.4 months, p¼0.03). Thus, in period 1 the OS for patients relapsing with PPs or EMPs was 7.5 and 8.7 months, respectively (p¼0.1) while in period 2 the OS was 20.8 and 14.5 months for patients relapsing with PPs and EMPs, respectively (p¼0.08). Conclusions: EMPs are more frequent at relapse that at diagnoses (2.6% versus 6.6%) while the incidence of PPs is similar at diagnosis and at relapse (17.1% versus 15%). The development of Ps at relapse is significantly higher in patients who had Ps at diagnoses (43% versus 14.6%). Patients with PPs at diagnosis had similar survival than those without Ps while patients with EMPs had poorer outcome than those with PPs or patients with no soft-tissue involvement, both at diagnosis and at relapse.
PS-193 3
2
Hospital Clínic, Barcelona, Barcelona; Hospital Clinic, Barcelona,
Catalonia; 3Hospital Clinic, Barcelona, Spain; 4Hospital Clínic de Barcelona / IDIBAPS, Barcelona, Barcelona
Transcriptional Programs Associated with Extra-medullary Tumor Progression in Multiple Myeloma Daeun Ryu,1 Hae-Ock Lee,2 Seok Jin Kim,3 Woong-Yang Park,4 Kihyun Kim5 1
Samsung Genome Institute, Gangnam-gu, Seoul; 2Samsung Genome Institute; 3Samsung Medical Center, Sungkyunkwan University School of Medicine; 4Samsung Genome Institute, Sung-
Introduction: Plasmacytomas (Ps) are frequent in patients with multiple myeloma (MM) and are considered to be associated with poor prognosis. There are two types of Ps: 1) paraskeletal plasmacytomas (PPs) consisting of soft-tissue masses arising from focal bone lesions and 2) extramedullary plasmacytomas (EMPs) consisting of soft-tissue masses with no contact with bone. However, the outcome of patients who develop Ps at diagnoses or at relapse as well as the outcome of the two types of Ps is not well established. Aim: To analyze the incidence, characteristics and outcome of patients with MM and Ps treated at our institution between 19702014 as well as the outcome of these patients before (period 1: 1970-1999) and after (period 2: 2000-2014) the introduction of novel drugs. Patients: A total of 1.116 multiple myeloma patients
kyunkwan University School of Medicine; 5Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Multiple myeloma is an incurable cancer of plasma cells. A subset of patients acquires treatment resistance and succumbs to rapid progression. Genetic heterogeneity is suspected as a main culprit for the development of or bona fide treatment resistance. Genetic heterogeneity could be assessed by inferring sub-clonal populations from whole exome or genome sequencing of the bulk tumors or by direct detection of somatic mutations in single tumor cell DNAs. However, the DNA analysis alone cannot solve how the mutational heterogeneity contributes to the pathology or treatment resistance.
16th International Myeloma Workshop March 1-4, 2017
- e107
University Hospitals Birmingham NHS Foundation Trust, Birming-
ham, West Midlands; 2University of Birmingham, Birmingham, United Kingdom; 3Royal Wolverhampton Hospitals, Wolverhampton, United Kingdom
Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are characterised by the accumulation of malignant plasma cells within bone marrow and lead to a range of abnormalities in the peripheral blood T cell repertoire. We investigated the level of inflammatory chemokines within the bone marrow and blood of patients with MGUS and MM and related this to the pattern of chemokine receptor expression on T cells in both compartments. The expression of a wide range of chemokine ligands for CXCR3 and CCR4 was markedly increased within the bone marrow of patients with MGUS and MM compared to healthy donors. The most marked effects were seen for CCL4 and CXCL9 which were increased by 4 and 6 fold respectively in the bone marrow of patients with myeloma. The expression of CXCR3 and CCR4, the major TH1 and TH2-associated chemokine receptors, was increased substantially on T cells within the bone marrow of patients whereas the percentage of CXCR3-expressing T cells within blood was correspondingly decreased. The presence of even small numbers of neoplastic plasma cells can therefore generate an inflammatory chemokine tumour microenvironment. This leads to the recruitment and retention of specific T cell subsets and is likely to underlie many of the features regarding the nature of the peripheral T cell repertoire in these patients. This local inflammatory reaction may represent a tumour-specific immune response or may itself play an important role in tumour progression and as such may offers a potential novel target for therapeutic intervention.
PS-192 Plasmacytomas in Multiple Myeloma: 45-Years Experience from a Single Institution 1
2
a
Laura Rosiñol, Raquel Jiménez, M Teresa Cibeira, Carlos Fernández de Larrea,4 Esther Bladé,3 Natalia Tovar,3 Joan Blade3 1
(548 males, 568 females) were diagnosed and treated at our institution from January 1970 to December 2014. Results: Overall, 220 patients (19.7%) had Ps at diagnoses (17.1% PPs and 2.6% EMPs). The incidence of PPs in period 1 was 12.9% versus 21.6% in period 2 (p<0.0001) while the incidence of EMPs remained unchanged over the years (2.5% versus 2.6% in periods 1 and 2, respectively). The median OS of patients with PPs was 3.5 years (2.1 years in period 1 and 5.2 years in period 2) while the median OS of patients with EMPs was 1.8 years (1.3 years in period 1 and 3.9 years in period 2) being the diference in OS statistically significant between patients with PPs and EMPs (p¼0.03). The OS of patients without Ps was 3.4 years (2.6 years in period 1 and 4.8 years in period 2) which was similar to the OS of patients with PPs (p¼0.5) and significantly longer than that observed in patients with EMPs (p¼0.03). The overall incidence of Ps at relapse was 21.6% (15% PPs and 6.6% EMPs). 43% of patients with Ps at diagnoses developed Ps at first or subsequent relapses versus 14.6% of patients without Ps at diagnoses (p<0.0001). The OS from the time of relapse with Ps was significantly longer in those who relapsed with PPs compared with patients who developed EMPs (median 11.4 versus 10.4 months, p¼0.03). Thus, in period 1 the OS for patients relapsing with PPs or EMPs was 7.5 and 8.7 months, respectively (p¼0.1) while in period 2 the OS was 20.8 and 14.5 months for patients relapsing with PPs and EMPs, respectively (p¼0.08). Conclusions: EMPs are more frequent at relapse that at diagnoses (2.6% versus 6.6%) while the incidence of PPs is similar at diagnosis and at relapse (17.1% versus 15%). The development of Ps at relapse is significantly higher in patients who had Ps at diagnoses (43% versus 14.6%). Patients with PPs at diagnosis had similar survival than those without Ps while patients with EMPs had poorer outcome than those with PPs or patients with no soft-tissue involvement, both at diagnosis and at relapse.
PS-193 3
2
Hospital Clínic, Barcelona, Barcelona; Hospital Clinic, Barcelona,
Catalonia; 3Hospital Clinic, Barcelona, Spain; 4Hospital Clínic de Barcelona / IDIBAPS, Barcelona, Barcelona
Transcriptional Programs Associated with Extra-medullary Tumor Progression in Multiple Myeloma Daeun Ryu,1 Hae-Ock Lee,2 Seok Jin Kim,3 Woong-Yang Park,4 Kihyun Kim5 1
Samsung Genome Institute, Gangnam-gu, Seoul; 2Samsung Genome Institute; 3Samsung Medical Center, Sungkyunkwan University School of Medicine; 4Samsung Genome Institute, Sung-
Introduction: Plasmacytomas (Ps) are frequent in patients with multiple myeloma (MM) and are considered to be associated with poor prognosis. There are two types of Ps: 1) paraskeletal plasmacytomas (PPs) consisting of soft-tissue masses arising from focal bone lesions and 2) extramedullary plasmacytomas (EMPs) consisting of soft-tissue masses with no contact with bone. However, the outcome of patients who develop Ps at diagnoses or at relapse as well as the outcome of the two types of Ps is not well established. Aim: To analyze the incidence, characteristics and outcome of patients with MM and Ps treated at our institution between 19702014 as well as the outcome of these patients before (period 1: 1970-1999) and after (period 2: 2000-2014) the introduction of novel drugs. Patients: A total of 1.116 multiple myeloma patients
kyunkwan University School of Medicine; 5Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Multiple myeloma is an incurable cancer of plasma cells. A subset of patients acquires treatment resistance and succumbs to rapid progression. Genetic heterogeneity is suspected as a main culprit for the development of or bona fide treatment resistance. Genetic heterogeneity could be assessed by inferring sub-clonal populations from whole exome or genome sequencing of the bulk tumors or by direct detection of somatic mutations in single tumor cell DNAs. However, the DNA analysis alone cannot solve how the mutational heterogeneity contributes to the pathology or treatment resistance.
16th International Myeloma Workshop March 1-4, 2017
- e107