Publications by authors named "B J Pender"
CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).
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- - Immune effector cell-associated hematotoxicity (ICAHT) significantly affects patients undergoing CAR T-cell therapy, and the factors linked to severe forms of it are not well understood.
- - Researchers identified key pre-infusion and post-infusion factors that predict early severe ICAHT in a study involving 691 patients; these included disease type, blood counts, inflammatory and coagulopathy markers.
- - Two predictive models (eIPMPre and eIPMPost) were developed and validated, showing strong accuracy in predicting severe ICAHT, with the post-infusion model being particularly effective; an online tool for individualized predictions is available for use.
More than half of the patients treated with CD19-targeted chimeric antigen receptor (CAR) T-cell immunotherapy for large B-cell lymphoma (LBCL) do not achieve durable remission, which may be partly due to PD-1/PD-L1-associated CAR T-cell dysfunction. We report data from a phase 1 clinical trial (NCT02706405), in which adults with LBCL were treated with autologous CD19 CAR T cells (JCAR014) combined with escalating doses of the anti-PD-L1 monoclonal antibody, durvalumab, starting either before or after CAR T-cell infusion. The addition of durvalumab to JCAR014 was safe and not associated with increased autoimmune or immune effector cell-associated toxicities.
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- A study of 44 patients receiving a second CAR T-cell infusion (CART2) found low severe toxicity rates and varied complete response rates across different types of B-cell cancers.
- Key findings indicate that certain pretreatment factors, like using specific lymphodepletion methods and increasing doses for the second infusion, can significantly improve patient outcomes and suggest strategies for future CAR T-cell therapy trials.
We previously reported a 24% 1-year relapse rate in 93 older or medically unfit patients with CD20 B cell malignancies after allogeneic hematopoietic cell transplantation (HCT) with low-intensity conditioning. The current prospective study tested the hypothesis that disease relapse could be reduced and overall survival (OS) improved by peritransplantation administration of rituximab (RTX). Sixty-three patients received RTX (375 mg/m/day) on days -3, +10, +24, and +38 along with 2 to 3 Gy total body irradiation with or without fludarabine (30 mg/m for 3 days).
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