Frontline immunotherapeutic combination strategies in adult B-cell acute lymphoblastic leukemia: reducing chemotherapy intensity and toxicity and harnessing efficacy.

Using immunotherapeutic agents like inotuzumab ozogamicin (InO), blinatumomab, or chimeric antigen receptor T (CAR T)-cell therapy in frontline adult B-cell acute lymphoblastic leukemia (B-ALL) therapy is promising. These agents are mostly well tolerated and have different toxicity profiles than conventional chemotherapy, enabling their combination with chemotherapy. Additionally, they have often been shown to overcome the traditional adverse ALL risk features.

Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia.

Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.

Outcomes of Patients With Treated Secondary Acute Myeloid Leukemia: A High-Risk Subtype That Warrants an Independent Prognostic Designation.

Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN.

Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent.

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery.

Clinical interrogation of TP53 aberrations and its impact on survival in patients with myeloid neoplasms.

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes.

Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma.

Optimal frontline use of active agents in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is prudent to improve outcomes. We report the long-term follow-up of the phase 2 trial of HyperCVAD with nelarabine and pegylated asparaginase (Original cohort). In the latest protocol iteration venetoclax was added to the induction/consolidation regimen (Venetoclax cohort).

Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial.

Background: Advanced phase Philadelphia chromosome-positive myeloid disease-consisting of chronic myeloid leukaemia in the myeloid blast phase and in the accelerated phase, and Philadelphia chromosome-positive acute myeloid leukaemia-is associated with poor outcomes. Although previous studies have suggested the benefit of chemotherapy and BCR::ABL1 tyrosine kinase inhibitor combinations, the optimal regimen is uncertain and prospective studies for this rare group of diseases are scant. Preclinical and retrospective clinical data suggest possible synergy between the BCL-2 inhibitor venetoclax and BCR::ABL1 tyrosine kinase inhibitors.

Outcomes of Patients With Newly Diagnosed AML and Hyperleukocytosis.

Purpose: AML presenting with hyperleukocytosis is associated with poor outcomes. We aim to understand the factors associated with early mortality and overall survival (OS) to help guide management and improve early mortality.

Methods: We retrospectively reviewed data from 129 consecutive patients with newly diagnosed AML and a WBC count ≥100 × 10/L between January 2010 and April 2020.

Lower intensity therapy with cladribine/low dose cytarabine/venetoclax in older patients with acute myeloid leukemia compares favorably with intensive chemotherapy among patients undergoing allogeneic stem cell transplantation.

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age who underwent SCT after intensive chemotherapy.

Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study.

Purpose: Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established.

Methods: We performed an international multicenter retrospective study of patients with RT who received CAR-T.

A phase 1/2 study of mini-hyper-CVD plus venetoclax in patients with relapsed/refractory acute lymphoblastic leukemia.

Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles.

SOHO State of the Art Updates and Next Questions | Next Questions: Acute Lymphoblastic Leukemia.

The integration of immune and targeted therapies into the treatment of acute lymphoblastic leukemia (ALL) has significantly improved outcomes, reduced the intensity and duration of chemotherapy, and the reliance on allogeneic stem cell transplantation (SCT). In younger patients with Philadelphia chromosome (Ph)-negative ALL, treatment with Hyper-CVAD and blinatumomab +/- inotuzumab has improved the 3-year overall survival (OS) to above 85%. In older patients, using less intensive chemotherapy (mini-Hyper-CVD) in combination with inotuzumab and blinatumomab has improved the 5-year OS rate to 50%.

Phase 2 study of inotuzumab ozogamicin for measurable residual disease in acute lymphoblastic leukemia in remission.

The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the setting of MRD may improve outcomes. Patients with ALL in first complete remission (CR1) or beyond (CR2+) with MRD ≥ 1 × 10-4 were enrolled in this phase 2 trial.

An Update on the Management of Advanced Phase Chronic Myeloid Leukemia.

Purpose Of Review: While most patients with chronic myeloid leukemia (CML) present in a chronic phase and are expected to have a normal life expectancy, some patients present with or progress to a more aggressive accelerated phase (AP) or blast phase (BP) of CML. Herein, we discuss the diagnostic considerations of advanced phase CML and review its contemporary management.

Recent Findings: Later-generation, more potent BCR::ABL1 tyrosine kinase inhibitors (TKIs) such as ponatinib may result in superior outcomes in patients with advanced phase CML.

Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies.

Purpose: Treatment outcomes in patients with relapsed/refractory (R/R) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remains dismal. On the basis of both extensive preclinical data and emerging clinical data, treatment with bromodomain and extra-terminal domain inhibitors (BETi) is a potential approach for patients with high-risk myeloid malignancies.

Patients And Methods: We conducted a phase I trial to study the safety and efficacy of PLX51107 (BETi) and azacitidine combination therapy in patients with R/R AML and high-risk (HR) MDS and studied mechanisms of resistance to the combination therapy.

Blastic plasmacytoid dendritic cell neoplasm: a comprehensive review in pediatrics, adolescents, and young adults (AYA) and an update of novel therapies.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can involve the bone marrow, peripheral blood, skin, lymph nodes, and the central nervous system. Though more common in older adults, BPDCN has been reported across all age groups, including infants and children. The incidence of pediatric BPDCN is extremely low and little is known about the disease.

Venetoclax abrogates the prognostic impact of splicing factor gene mutations in newly diagnosed acute myeloid leukemia.

Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut.