- p57Kip2 regulates embryonic stem cell expansion
- Changes in survival of CLL patients with COVID-19 infection
- Phase 1 study of CD19/22 CAR T cells
- Mechanism of antiplatelet antibody formation following ChADOx1 nCov-19 administration
- Tumor-specific characteristics that predict poor outcome after CAR-T therapy
- Special Report: Recommendations for trial design and staging of primary cutaneous lymphoma
Immune thrombocytopenia and adenoviral SARS-COV2 vaccines, genomics, and a risk assessment model of anti-CD19 CAR T-cell treatment outcomes in lymphoma
In this week’s episode we’ll discuss the factors influencing the development of immune thrombocytopenia after administration of the ChAdOx1 nCov-19 vaccine, learn about the genomic features underlying anti-CD19 CAR T-cell treatment failure in lymphoma, and introduce a new predictive model for risk assessment before CAR T-cell therapy for large B-cell lymphoma.
Niemann and colleagues used the Danish clinical registry to provide a longitudinal view of the outcomes of patients with chronic lymphocytic leukemia (CLL) who become infected with COVID-19. Overall, outcomes have improved during the era of the Omicron variants, with 30-day mortality across all patients with CLL declining from 23% to 2%. However, patients requiring hospital care continue to have 30-day mortality as high as 23%, suggesting that this population should be considered for close monitoring and preemptive antiviral therapy.
Thrombocytopenia and splenic platelet-directed immune responses after IV ChAdOx1 nCov-19 administration
Nicolai and colleagues studied vaccine-induced thrombotic thrombocytopenia (VITT) and immune thrombocytopenia (ITP) following adenovirus-based COVID-19 vaccine administration. They isolated and characterized antiplatelet antibodies from 27 patients with VITT and 26 patients with isolated thrombocytopenia following ChAdOx1 n-Cov-19 vaccination and modeled antibody formation in mice. Intravenous rather than intramuscular injection triggers platelet-adenovirus aggregates that are phagocytosed by splenic macrophages, leading to B-cell responses, suggesting that avoiding intravenous administration could obviate this complication.
Cataland and colleagues describe a clinical approach to the follow-up of patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) following acute hospitalization. The authors provide valuable recommendations for frequency of laboratory testing, timing of intervention with further immunosuppression, and monitoring for the known complications of iTTP.
Whole-genome sequencing reveals complex genomic features underlying anti-CD19 CAR T-cell treatment failures in lymphoma
Two articles investigate tumor characteristics that predict the failure of CD19-directed chimeric antigen receptor (CAR) T cells in the treatment of large B-cell lymphoma. In the first article, Jain et al report on the results of whole-genome sequencing of 51 tumor samples; they confirm that pretreatment complex structural variants, APOBEC mutational signature, reactive oxygen species-related genomic changes, and recurrent 3p21.31 chromosomal deletion predict CAR T failure...
CD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR
Shalabi et al report on a phase 1 trial of a bivalent chimeric antigen receptor (CAR) T-cell product targeting both CD19 and CD22, including some patients whose CAR T-cell therapy had failed. The complete response rate was 60% in all patients and 71% in those without prior CAR T-cell therapy. However, expansion and persistence of the CAR T cells are limited, and the investigators developed a new vector based on laboratory studies that may optimize the persistence of the bivalent vector in the future. Until then, proceeding to stem cell transplantation in responding patients is advised.