CD200 genotype is associated with clinical outcome of patients with multiple myeloma

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events

The direct and indirect effects of COVID‐19 pandemic in a real‐life hematological setting

Background: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. Aims: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. Methods and results: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). Conclusion: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker

Table_1_CD200 genotype is associated with clinical outcome of patients with multiple myeloma.docx

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.</p

Table_1_Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.docx

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.</p