TP53 Mutations are Associated with CD19 Negative Relapse and Inferior Outcomes after Blinatumomab in Adults with ALL.

Despite the success of the CD19xCD3 T cell engager blinatumomab in B-cell acute lymphoblastic leukemia (B-ALL), treatment failure is common and can manifest with antigen loss and extramedullary disease (EMD) relapse. To understand the impact of leukemia genetics on outcomes, we reviewed 267 adult patients with B-ALL treated with blinatumomab and used next generation sequencing to identify molecular alterations. Patients received blinatumomab for relapsed/refractory (R/R) disease (n=150), minimal residual disease (MRD+) (n=88), upfront as induction (n=10), or as consolidation in MRD- state (n=19).

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.

The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models.

Fludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease.

Patients with AML and measurable residual disease (MRD) undergoing allogeneic hematopoietic cell transplantation (HCT) may benefit from myeloablative conditioning (MAC) when feasible to reduce relapse risk. Fludarabine-Melphalan (FluMel) is a common reduced intensity conditioning (RIC) regimen; however, data in MRD+ patients is sparse. We performed a retrospective review of AML patients who underwent their first HCT (2016-2021) without morphologic disease at City of Hope who had pre-transplant marrow evaluated for MRD using multicolor flow cytometry (MFC) and received radiation-based MAC or FluMel conditioning.