In this week's episode, we'll learn about rapid, high-sensitivity diagnostic assays for TTP, or thrombotic thrombocytopenic purpura, that can reduce unnecessary treatments. After that: enhancing PD-1 blockade in relapsed/refractory extranodal NK/T-cell lymphoma. In a single-arm, phase 2 study, combined CD38 and PD-1 inhibition demonstrated durable responses and manageable safety. Finally, a lymphoma horror story with a happy ending. CREBBP mutations create a zombie enzyme that competes with its wild-type counterparts. By enforcing CD40 signaling, a bispecific antibody overcomes this effect and induces lymphoma cell death.

Featured Articles:

• Rapid ADAMTS13 activity assays for thrombotic thrombocytopenic purpura: a systematic review and meta-analysis
• Efficacy of combined CD38 and PD-1 inhibition with isatuximab and cemiplimab for relapsed/refractory NK/T-cell lymphoma
• Blunted CD40-responsive enhancer activation in CREBBP-mutant lymphomas can be restored by enforced CD4 T-cell engagement

In this week's episode we’ll learn more about a novel mouse model that recapitulates many of the properties of human sickle cell SC disease; results from the induction phase of the risk-adapted MIDAS trial of isatuximab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed, transplant-eligible multiple myeloma; and a link between splicing factor mutations and competitive fitness in myelodysplastic syndrome stem cells.

Featured articles:

• A novel mouse model of hemoglobin SC disease reveals mechanisms underlying beneficial effects of hydroxyurea
• Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial
• Cell-autonomous dysregulation of interferon signaling drives clonal expansion of SRSF2-mutant MDS stem/progenitor cells

In this week's episode, we'll learn about using AI to assess transplant risk in myelofibrosis. In a step toward personalized medicine, researchers report on a machine learning model that identifies 25% of patients with poor outcomes. After that: preventing priapism in men with sickle cell anemia. A recent phase 2 feasibility study shows high rates of recruitment, retention, and adherence to oral therapies, coupled with a significant reduction in the risk of this difficult complication. Finally, new research indicates that hallmarks of terminal T-cell exhaustion are absent in multiple myeloma, from diagnosis through maintenance therapy. We explore these provocative and counterintuitive findings arising from profiling of blood and marrow samples.

Featured Articles:

• Use of machine learning techniques to predict poor survival after hematopoietic cell transplantation for myelofibrosis
• A controlled trial for preventing priapism in sickle cell anemia: hydroxyurea plus placebo vs hydroxyurea plus tadalafil
• Hallmarks of T-cell exhaustion and antigen experience are absent in multiple myeloma from diagnosis to maintenance therapy