Blinatumomab for the treatment of acute lymphoblastic leukemia in a real-world setting: clinical vignettes.

Blinatumomab, a CD19/CD3 bispecific T-cell engager; inotuzumab ozogamicin (INO), a CD22 antibody drug conjugate; and chimeric-antigen receptor (CAR) T-cell constructs are novel immune-therapeutic options for treatment of acute lymphoblastic leukemia (ALL). The use of blinatumomab has recently expanded to multiple B-ALL treatment settings. Despite the efficacy of blinatumomab, its use can be challenging in the real-world because of limited experience with its administration and management of toxicities.

Dose-Dense Mini-Hyper-CVD, Inotuzumab Ozogamicin and Blinatumomab Achieves Rapid MRD-Negativity in Philadelphia Chromosome-Negative B-cell Acute Lymphoblastic Leukemia.

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients And Methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia.

Background: Historically, adults with relapsed-refractory acute lymphoblastic leukemia (ALL) experienced poor outcomes with intensive chemotherapy. This mature analysis explores the benefit of the addition of sequential blinatumomab to low-intensity mini-Hyper-CVD chemotherapy with inotuzumab ozogamicin in this setting.

Methods: Mini-Hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 83% dose reduction) was combined with inotuzumab during the first 4 courses.

Electron-Phonon Interaction Contribution to the Total Energy of Group IV Semiconductor Polymorphs: Evaluation and Implications.

In density functional theory (DFT)-based total energy studies, the van der Waals (vdW) and zero-point vibrational energy (ZPVE) correction terms are included to obtain energy differences between polymorphs. We propose and compute a new correction term to the total energy, due to electron-phonon interactions (EPI). We rely on Allen's general formalism, which goes beyond the quasi-harmonic approximation (QHA), to include the free energy contributions due to quasiparticle interactions.

Incidence of adverse effects in patients receiving ponatinib with concomitant azole antifungals.

Ponatinib plus Hyper-CVAD yields a five-year overall survival of 73% in patients with Philadelphia-positive acute lymphoblastic leukemia. Ponatinib dose intensity is associated with increased incidence of adverse effects (AEs), including vascular events. Ponatinib combined with azole antifungals may further increase the risk of AEs due to increased ponatinib exposure.

The influence of drug prices, new availability of inexpensive generic imatinib, new approvals, and post-marketing research on the treatment of chronic myeloid leukaemia in the USA.

Several research and market developments in the past 5 years could influence front-line and subsequent-line strategies in chronic myeloid leukaemia. These developments include the increased availability of effective and safe generic imatinib at affordable prices, studies showing that doses of tyrosine kinase inhibitors (TKIs) lower than the approved dose are effective and less toxic, studies showing that dose-adjusted ponatinib therapy at a reduced dose is effective and substantially safer than approved doses, and the approval of asciminib as third-line therapy in 2021. With the availability of an affordable generic imatinib, all patients with chronic myeloid leukaemia globally should be able to access a lifetime supply.

Central Nervous System Involvement in Adults with Acute Leukemia: Diagnosis, Prevention, and Management.

Purpose Of Review: Recent treatment advances in both acute myeloid leukemia and acute lymphoblastic leukemia have drastically improved outcomes for these diseases, but central nervous system (CNS) relapses still occur. Treatment of CNS disease can be challenging due to the impermeability of the blood-brain barrier to many systemic therapies.

Recent Findings: The diagnosis of CNS leukemia relies on assessment of clinical symptoms, cerebrospinal fluid sampling for conventional cytology and/or flow cytometry, and neuroimaging.

Clinical and molecular characteristics and treatment patterns of adolescent and young adult patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) rarely presents in adolescent and young adult (AYA) patients (patients aged 15-39 years). Disease characteristics and outcomes of AYA patients with CLL are not well understood, particularly in the era of novel oral targeted therapies. We analysed outcomes of 227 AYA patients with CLL diagnosed in the last two decades and evaluated at our institution.

The clinical development of antibody-drug conjugates - lessons from leukaemia.

Advances in our understanding of cancer biology have enabled drug development to progress towards better targeted therapies that are both more effective and safer owing to their lack of off-target toxicities. In this regard, antibody-drug conjugates (ADCs), which have the potential to combine the selectivity of therapeutic antibodies with the cytotoxicity of highly toxic small molecules, are a rapidly developing drug class. The complex and unique structure of an ADC, composed of a monoclonal antibody conjugated to a potent cytotoxic payload via a chemical linker, is designed to selectively target a specific tumour antigen.

Long-term follow-up of salvage therapy using a combination of inotuzumab ozogamicin and mini-hyper-CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia.

Background: The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low-intensity mini-hyper-CVD (mini-hyper-CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m × 4 doses) chemotherapy has shown encouraging results.

Glasdegib plus low-dose cytarabine for acute myeloid leukemia: Practical considerations from advanced practitioners and pharmacists.

Objective: Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC).

CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies.

CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated in leukemic stem cells relative to non-neoplastic hematopoietic stem cells, which makes it a useful diagnostic and therapeutic biomarker in hematologic malignancies. Varying levels of evidence have shown that CD123-targeted therapy represents a promising therapeutic approach in several cancers.

Optimizing patient selection for treatment-free remission.

The advent of BCR-ABL1 tyrosine kinase inhibitors has revolutionized the treatment and prognosis of chronic myeloid leukemia. Life expectancy for patients with chronic phase chronic myeloid leukemia now nears that of the healthy population; however, optimal outcomes require continuous tyrosine kinase inhibitor administration, which can impact patient quality of life. Consequently, the concept of treatment-free remission has been explored in patients achieving and sustaining a deep molecular response.

Treating Leukemia in the Time of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic poses several challenges to the management of patients with leukemia. The biology of each leukemia and its corresponding treatment with conventional intensive chemotherapy, with or without targeted therapies (venetoclax, FLT3 inhibitors, IDH1/2 inhibitors, Bruton's tyrosine kinase inhibitors), introduce additional layers of complexity during COVID-19 high-risk periods. The knowledge about COVID-19 is accumulating rapidly.

Treatment-free remission in chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) represent a major breakthrough in the treatment of chronic myeloid leukemia (CML). Thanks to these agents, CML has been transformed from a disease with limited treatment options and a dismal prognosis into a more indolent disease with survival comparable to that of the general population. The need for ongoing TKI therapy remains controversial for several reasons, including cost and toxicity.

The face of remission induction.

Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors, including age, prior haematologic disorders, and comorbidities. Despite the diverse disease biology, the standard of care for remission induction therapy has changed very little since its inception in 1973. Next generation sequencing has helped to increase our knowledge of the disease pathogenesis, allowing us to develop targeted and possibly more effective treatment options.

Quizartinib in the treatment of FLT3-internal-tandem duplication-positive acute myeloid leukemia.

FLT3 mutations, characterized by an internal-tandem duplication or missense mutations in the tyrosine kinase domain, are observed in a third of patients with newly diagnosed acute myeloid leukemia. mutations are associated with high relapse rates and short overall survival with conventional chemotherapy. Several tyrosine kinase inhibitors targeting FLT3 have been developed in an effort to improve survival and therapeutic options.

Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia.

Background: Dasatinib, a potent Bcr-Abl tyrosine kinase inhibitor, is approved for the treatment of chronic-phase chronic myeloid leukemia (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100-mg daily dose.

SOHO State of the Art Update and Next Questions: Advances in the Treatment of Adult Acute Lymphoblastic Leukemia.

The treatment of adult acute lymphoblastic leukemia (ALL) has largely followed the successful pediatric model that uses multi-agent chemotherapy regimens. Although cytotoxic chemotherapy can induce complete remissions, elderly patients are frequently unable to tolerate its intensity owing to toxicities and comorbidities. Elderly patients particularly often relapse, leading to a 5-year overall survival (OS) of only 20%.