Cover ImageChimeric antigen receptor (CAR) T cells have been approved in myeloma as a late-line therapy. In this setting, their performance is likely suboptimal due to patients’ weakened immune systems, higher disease burden, and selection of multi-therapy resistance. There is hope that moving CAR T-cell treatment to a frontline setting may open a safer and more effective avenue of treatment. In this issue, Garfall and colleagues present pioneering work with a phase I clinical trial of dual-targeting CAR T cells as an early- versus late-line therapy supporting safety and feasibility of the treatment. At the same time, the lower-than-expected complete response rate suggests that patient-specific factors beyond those addressed by early-line use continue to shape the outcomes. The cover image by Tetiana Sichkarenko illustrates how an optimal path out of the woods is fraught with challenges unique to the nature of each setting and its explorer. For details, see the article on p. 118.Close Modal
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In This Issue
In the Spotlight
Impaired SARS-CoV-2 Variant Neutralization and CD8+ T-cell Responses Following 3 Doses of mRNA Vaccines in Myeloma: Correlation with Breakthrough Infections
Triple-vaccinated myeloma patients lack CD8 responses and display suboptimal antibody responses, particularly against newer SARS-CoV-2 variants. Live-virus neutralization activity, rather than antibody titers, correlate with breakthrough infections.
Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy
A Phase I trial of early-line anti-BCMA and anti-CD19 CAR T cells in high-risk multiple myeloma patients demonstrated safety and feasibility of dual-target CAR T therapy with maintenance as an early-line treatment.
Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Emerges from Preleukemic TP53-Mutant Clonal Hematopoiesis
Comprehensive genomics reveal high prevalence of low hypodiploidy in older patients with B-ALL and track its origin to TP53-deficient age-associated clonal hematopoiesis.
In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities
A multiplex-edited mouse model of Richter syndrome transformation from CLL reveals dysregulated signaling pathways and potential therapeutic targets.