Impact of culture vessel materials on biomanufacturing of dendritic cell-based immunotherapies in closed systems.

Dendritic cell-based immunotherapy is a promising strategy to treat malignant diseases. manufacturing of dendritic cells conventionally relies on culturing primary monocytes in dishes or vessels made from tissue culture treated polystyrene. For clinical applications, the implementation of closed culture vessels such as cell culture bags is highly desirable to minimize the risks of contamination and allow automated fluid handling.

Switching TKIs during CML therapy is frequent, mostly driven by intolerance, and does not affect survival: a prospective Quebec registry study.

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Characteristics of relapsed/refractory diffuse large B-cell lymphoma patients with durable responses to maveropepimut-S, pembrolizumab, and cyclophosphamide: Long-term follow-up from the SPiReL trial.

Introduction: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have an unmet medical need. The objective of this trial was to assess the efficacy and toxicities of a novel triple immunotherapy regimen-pembrolizumab, low-dose cyclophosphamide, and maveropepimut-S (MVP-S). This regimen was designed to activate tumor-specific T cells by targeting the tumor-associated antigen survivin with MVP-S and reducing two important T cell inhibitory pathways: T cell exhaustion and regulatory T cells with pembrolizumab and metronomic cyclophosphamide, respectively.

Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment-free remission after failing the first attempt with imatinib: Treatment-free Remission Accomplished by Dasatinib (TRAD) study.

Multiple studies have reported a significant treatment-free remission (TFR) rate of 50%-60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re-initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re-therapy in patients who failed the first TFR (TFR1) attempt.

PD-L1 expression predicts efficacy in the phase II SPiReL trial with MVP-S, pembrolizumab, and low-dose CPA in R/R DLBCL.

Background: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options.

Methods: R/R DLBCL patients, who were mostly ineligible for ASCT due to age or comorbidities, were treated with maveropepimut-S (MVP-S, previously DPX-Survivac) a survivin directed T cell educating therapy, pembrolizumab, and intermittent low-dose cyclophosphamide.

Findings: We identified, using univariate analysis, a subset of patients with enhanced ORR, PFS and DOR.

BCR-ABL1 transcript doubling time as a predictor for treatment-free remission failure after imatinib discontinuation in chronic myeloid leukaemia in chronic phase.

The doubling time (DT) of the BCR-ABL1 quantitative polymerase chain reaction (qPCR) transcript level reflects the re-growing fraction of leukaemic cells after discontinuation of tyrosine kinase inhibitor (TKI). The present study analyzed monthly DT within six months after imatinib discontinuation in 131 patients. Monthly DT was calculated as x = ln(2)/K, where x is the DT and K is the fold BCR-ABL1 change from the previous value divided by the number of days between each measurement.

Optimal duration of imatinib treatment/deep molecular response for treatment-free remission after imatinib discontinuation from a Canadian tyrosine kinase inhibitor discontinuation trial.

Although total duration of tyrosine kinase inhibitor (TKI) therapy and of molecular response at 4 log reduction or deeper (MR4) correlates with treatment-free remission (TFR) success after TKI discontinuation, the optimal cut-off values of the duration remain unresolved. Thus, 131 patients were enrolled into the Canadian TKI discontinuation study. The molecular relapse-free survival (mRFS) was defined from imatinib discontinuation till molecular recurrence, that is, major molecular response (MMR) loss and/or MR4 loss.

Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia.

Background: In the current study, the authors determined whether adhering to molecular monitoring guidelines in patients with chronic myeloid leukemia (CML) is associated with major molecular response (MMR) and assessed barriers to adherent monitoring.

Methods: Newly treated patients with CML from the Quebec province-wide CML registry from 2005 to 2016 were included. Timely polymerase chain reaction (tPCR) was defined as the molecular assessment of BCR-ABL1 at the 3-month, 12-month, and 18-month time points from the initiation of tyrosine kinase inhibitor (TKI) therapy.

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis: perspectives and approaches.

Multiple sclerosis (MS) is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies (DMTs) for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease.

Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia.

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, both as first-line therapy and after imatinib intolerance or resistance. While generally well tolerated, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors, and outcomes associated with pleural effusion were assessed in two phase 3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11 trials that evaluated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib (including DASISION and 034/Dose-optimization).

Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype.

When to Stop Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia.

Strict criteria for when to stop tyrosine kinase inhibitor (TKI) therapy in clinical practice are not easily defined without an agreement on what probability of achieving a treatment-free remission (TFR) constitutes a medically acceptable standard and consideration of the potential medical risks of continued TKI therapy and/or patient preferences. Patients in sustained deep molecular response (DMR) have no significant chronic myelogenous leukemia-related risk of progression and death, and thus, safety is of paramount importance. Patients with prior history of advanced disease, additional chromosomal abnormalities (ACA), atypical transcripts, TKI resistance, high Sokal score, or who cannot be relied upon to come for regular molecular monitoring should generally be excluded from TKI cessation in clinical practice.

Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial.

Background: Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis.

Methods: We did this phase 2 single-arm trial at three hospitals in Canada.

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years.

Evolving Therapeutic Options for Polycythemia Vera: Perspectives of the Canadian Myeloproliferative Neoplasms Group.

Polycythemia vera (PV) is a clonal stem cell disorder characterized by erythrocytosis and associated with burdensome symptoms, reduced quality of life, risk of thrombohemorrhagic complications, and risk of transformation to myelofibrosis and acute myeloid leukemia. The discovery of the JAK2 V617 mutation marked a significant milestone in understanding the pathophysiology of the disease and subsequently the diagnostic and therapeutic approaches. The current diagnostic criteria for PV are based on hemoglobin level and presence of the JAK2 V617 mutation.

The cost-effectiveness of stem cell transplantations from unrelated donors in adult patients with acute leukemia.

Objective: Hematopoietic stem cell transplantation is an accepted treatment of hematological malignancies, but the cost-effectiveness of this technology has not been fully explored. This study aims to assess the cost-effectiveness of stem cell transplantation from either cord blood or bone marrow/peripheral blood compared with no transplantation in adult patients with acute leukemias not expected to be cured with chemotherapy.

Methods: A systematic review was performed to estimate the efficacy of unrelated cord blood and bone marrow/peripheral blood stem cells (BM/PBSC) transplantations in adults with acute leukemia.

Comparison of peripheral blood progenitor cell yield from standard chemotherapy used in the treatment of lymphoid malignancies and high-dose cyclophosphamide: a retrospective review of 141 patients.

Background: Peripheral blood progenitor cells (PBPCs) are often collected after mobilization with high-dose cyclophosphamide (HDC) combined with growth factors. HDC may not be needed for PBPC mobilization, and patients with lymphoid malignancies can be harvested with treatment regimens of chemotherapy.

Study Design And Methods: A retrospective analysis was performed on 141 patients with lymphoma or multiple myeloma whose PBPCs were harvested after chemotherapy.