Subject(s)
Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Doxorubicin/therapeutic use , Multiple Myeloma/drug therapy , Adult , Aged , Bortezomib/pharmacology , Dexamethasone/pharmacology , Doxorubicin/pharmacology , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Treatment OutcomeSubject(s)
Multiple Myeloma/mortality , Multiple Myeloma/therapy , Stem Cell Transplantation , Adult , Aged , Autografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Survival RateSubject(s)
Multiple Myeloma , Proteasome Inhibitors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Boron Compounds , Dexamethasone/therapeutic use , Glycine/analogs & derivatives , Humans , Lenalidomide/therapeutic use , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Neoplasm Recurrence, Local/drug therapy , Proteasome Inhibitors/therapeutic useABSTRACT
High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is the standard of care for eligible multiple myeloma (MM) patients with improved progression-free and overall survival. We reviewed the ambulatory care unit pathway for MM patients who underwent HDT/ASCT in a tertiary hospital to assess safety efficacy and outcomes. We concluded that the ambulatory care model offered for MM patients undergoing HDT/ASCT is a safe alternative pathway and highlighted further improvements.
Subject(s)
Antineoplastic Agents/adverse effects , Multiple Myeloma/therapy , Stem Cell Transplantation/adverse effects , Transplantation, Autologous/adverse effects , Adult , Aged , Ambulatory Care , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
PURPOSE: Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy. EXPERIMENTAL DESIGN: We undertook detailed characterization of T cells from bone marrow (BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression-free survival. RESULTS: We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared with healthy donors. Patients with higher frequencies of Tregs had shorter PFS and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared with patients with lower frequencies of Tregs. Analysis of CD4 and CD8 effectors revealed that low CD4effector (CD4eff):Treg ratio and increased frequency of PD-1-expressing CD4eff cells were independent predictors of early relapse over and above conventional risk factors, such as genetic risk and depth of response. Ex vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction. CONCLUSIONS: BM-infiltrating T-cell subsets, specifically Tregs and PD-1-expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies.
Subject(s)
Bone Marrow/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Multiple Myeloma/etiology , Multiple Myeloma/metabolism , Programmed Cell Death 1 Receptor/metabolism , T-Lymphocytes, Regulatory/immunology , Biomarkers, Tumor , Case-Control Studies , Cytokines/metabolism , Female , Humans , Lymphocyte Activation/immunology , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Male , Multiple Myeloma/diagnosis , Multiple Myeloma/mortality , Prognosis , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocyte Subsets/pathology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathologyABSTRACT
OBJECTIVE: Cytomegalovirus (CMV) is an opportunistic herpesvirus, and reactivation of infection is possible in immunocompromised patients. Historically, the risk for haematology patients is restricted to those treated with an allogeneic transplant or T-cell depleting agents. Bortezomib is a highly efficacious proteasome inhibitor widely used to treat multiple myeloma and light chain (AL) amyloidosis patients. The objective of this small prospective study was to quantify the risk of CMV reactivation associated with bortezomib treatment. METHODS: Fifty-seven consecutive multiple myeloma or AL amyloidosis patients commencing bortezomib-based therapy were included. Viral copy numbers were established at baseline and then at fortnightly intervals during treatment. Pre-emptive anti-viral treatment was initiated in patients with a viral load >7500 copies/mL. RESULTS: Reactivation of CMV was detected in 39% (n = 12/31) of seropositive bortezomib treated patients compared with 0% of CMV seronegative patients. Detectable DNAemia developed during the first two cycles of treatment in 83% (n = 10/12) patients. Anti-viral treatment was initiated in 42% (n = 5/12), but no cases of active CMV disease were seen. CONCLUSION: This study suggests that there is a substantial risk of CMV reactivation in CMV-seropositive plasma cell dyscrasia patients treated with bortezomib.
Subject(s)
Antineoplastic Agents/adverse effects , Bortezomib/adverse effects , Cytomegalovirus Infections/etiology , Cytomegalovirus , Immunoglobulin Light-chain Amyloidosis/complications , Multiple Myeloma/complications , Virus Activation/drug effects , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bortezomib/therapeutic use , Cytomegalovirus/drug effects , Cytomegalovirus/immunology , Female , Humans , Immunoglobulin Light-chain Amyloidosis/diagnosis , Immunoglobulin Light-chain Amyloidosis/drug therapy , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy , Prospective Studies , Viral LoadSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Aged , Clinical Trials as Topic , Drug Resistance, Neoplasm , Female , Humans , Male , Middle Aged , Multiple Myeloma/pathology , Recurrence , Retrospective Studies , Tertiary Care Centers , Treatment OutcomeABSTRACT
Hyponatraemia is the most common electrolyte disturbance encountered in clinical practice. Several causes of hyponatraemia are recognised and in many patients the aetiology may be multifactorial. An important cause is water intoxication and this is often iatrogenic. We present three patients, all of whom suffered from multiple myeloma, who illustrate different aspects of hyponatraemia, its causes and management.