Resimmune, an anti-CD3  recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma

Abstract

Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 -11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208. Resimmune, an anti-CD3ε recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma ABSTRACT MethodsThe Resimmune study was a single-arm, multicenter interpatient dose escalation phase 1 trial in patients with advanced CD3 + T-cell malignancies. The study was performed under the sponsorship of Angimmune, LLC, registered at clinical trials.gov as NCT00611208, and approved by Institutional Review Boards at the participating institutions. Thirty patients were treated with a single course of Resimmune at doses ranging from 2.5 to 11.25 μg/kg intravenously twice daily for 4 days. Eligibility and diagnosisPatients with CD3 + T-cell malignancies, diagnosed by morphological, histochemical, and cell surface criteria, in whom systemic therapy had failed were eligible for the study.

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“…Nonetheless, the presence of NAs was not associated with survival outcomes, and there was no correlation between NAs and the dose of eBAT received or the drug PK. These findings were similar to other studies with targeted toxin where antitoxin antibody titers did not correlate with antitumor activity [43]. Our results exceeded expectations for outcome of dogs with stage-I or stage-II HSA based on our historical data and on other published data from comparable populations treated with the standard of care [44, 45].…”

Innovative Treatment Concepts for Cutaneous T-Cell Lymphoma Based on Microenvironment Modulation

“…Clinical OR was 36% with 14 months of DOR for resimmune, and 30-49% for denileukin diftitox. Notably, AEs included vascular leak syndrome, vomiting, and fever [54,55]. Despite the significant AEs, approval was granted in the US for CTCL [23,24].…”

Innovative Behandlungskonzepte mit Modulation der Mikroumgebung beim kutanen T-Zell-Lymphom

“…Mit Resimmun wurde eine klinische Ansprechrate von 36% erzielt (bei 14 Monaten DOR), mit Denileukindiftitox waren es 30 - 49%. Die wichtigsten UE waren vaskuläres Leak-Syndrom, Erbrechen und Fieber [54,55]. Trotz erheblicher Toxizität wurde in den USA die Zulassung für CTCL erteilt [23,24].…”