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ANALYSIS OF EFFICACY AND SAFETY OF LONCASTUXIMAB TESIRINE (ADCT‐402) BY DEMOGRAPHIC AND CLINICAL CHARACTERISTICS IN RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA
Author(s) -
Radford J.,
Kahl B.,
Hamadani M.,
CarloStella C.,
O'Connor O.A.,
Ardeshna K.M.,
Feingold J.,
He S.,
Reid E.,
Solh M.,
Chung K.,
Heffner L.,
Ungar D.,
Caimi P.
Publication year - 2019
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.60_2629
Subject(s) - medicine , diffuse large b cell lymphoma , gastroenterology , nausea , adverse effect , neutropenia , anemia , lymphoma , refractory (planetary science) , oncology , toxicity , biology , astrobiology
refractory to prior therapy. CRS (according to the criteria by Lee et al. Blood 2014) occurred in 45 patients (23% G1, 24% G2, 3% G3, 1% G4). At the highest dose cohort (25 mg) >G3 CRS occurred in 3/8 pts at cycle 1, thereby preventing further dose escalation. One patient in the 25 mg cohort died of upper GI bleeding after an episode of severe CRS. All other CRS events were manageable and resolved, and patients were retreated without delay at the same dose at cycle 2, where only one additional CRS event was seen (G1). In the efficacy evaluable pts (n=84) the ORR and CR rate by investigator assessment (Lugano 2014 criteria) in aNHL (n=76) was 46% and 29%, and in FL (n=8) 63% and 50%, respectively. In the highest dose cohorts (10-25 mg) the ORR and CR rate in aNHL (n=38) was 55% and 37% indicating a dose-response relationship. CR was usually achieved at the first or second response assessments (C3 or C6) although in 4 aNHL pts late conversion from PR or SD to CR was observed at cycle 12. A patient with FL initially dosed at 15 μg who had progressed was retreated at 10 mg, achieving CR. After a median follow up of 3.8 months all but 2 CRs are still ongoing. Responses were seen across NHL subtypes and across prognostic factors such as disease burden, prior lines of therapy, and refractoriness to prior therapy. CD20-TCB exposure and receptor occupancy increased dosedependently across the investigated dose range. No anti-drugantibodies have been found. Mode of action was demonstrated by rapid and sustained T cell activation in peripheral blood and tumor biopsies. Conclusions: CD20-TCB is a novel 2:1 format T-cell-engaging bispecific antibody which displays highly promising clinical activity in heavily-pretreated NHL.