On Location ASH Annual Meeting
( 32 % CRs , 6 % PRs ), and these rates remained stable at six months post-infusion ( ORR = 37 %, with 30 % CRs and 7 % PRs ). Response at three months was “ key ,” Dr . Schuster said , with “ 95 percent of patients who were in CR at three months likely to stay in CR for years .”
Median overall survival ( OS ) and median duration of response were not reached , the six-month probability of OS was 64.5 percent ( 95 % CI 51.5-74.8 ; p value not reported ), and the six-month probability of being relapse-free was 73.5 percent ( 95 % CI 52.0-86.6 ; p value not reported ).
Response at three months was “ key ,” with “ 95 percent of patients who were in CR at three months likely to stay in CR for years .”
— STEPHEN J . SCHUSTER , MD
Safety analysis showed that 86 percent of all 99 patients who received tisagenlecleucel experienced a grade 3 or 4 adverse event ( AEs ). As with other CAR T-cell therapies , the most common any-grade AE was cytokine release syndrome ( CRS ), which occurred in 58 percent of infused patients ; CRS was grade 3 / 4 in 23 percent of patients . Fifteen percent of these patients received tocilizumab , and 11 percent of patients received corticosteroids to manage CRS , “ with good response ,” Dr . Schuster noted . Though neurologic events occurred in 21 percent of patients ( 12 % were grade 3 / 4 ), there were no deaths related to cerebral edema , the researchers added . Three deaths occurred within 30 days of infusion , all of which were considered related to disease progression ( not treatment or treatment-related AEs ).
The findings from this study are limited by the small number of patients and the lack of a comparator arm . Dr . Schuster added that the JULIET investigators are now looking at the causes for treatment failure in the patients who did not respond to tisagenlecleucel infusion . “ Loss of CD19 is the most common reason for failure in ALL , but accounts for only 10 to 20 percent of treatment failure in DLBCL ,” he said . “ In JULIET , the majority of [ treatment failures ] were because the tumor cells upregulated inhibitory ligands . … We have started a trial ‘ rescuing ’ patients whose disease progressed during T-cell expansion with the checkpoint inhibitor pembrolizumab .”
The authors report financial relationships with Novartis , which also provided funding for the study .
REFERENCE
Schuster SJ , Bishop MR , Tam CS , et al . Primary analysis of Juliet : A global , pivotal , phase 2 trial of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma . Abstract 577 . Presented at the 2017 American Society of Hematology Annual Meeting , December 11 , 2017 ; Atlanta , GA .
The 2018 ASH Annual Meeting will be held in San Diego , CA , December 1-4 .
Interim Results from the First-in-Human Trial of Antibody Drug Conjugate ADCT-402 in B-Cell Malignancies
In a first-in-human trial of loncastuximab tesirine , the CD19-targeting antibody drug conjugate ( ADC ) appeared to have encouraging efficacy as a single agent in patients with B-cell non-Hodgkin lymphomas ( NHLs ), with “ low-grade , but persistent toxicities ” and an overall response rate ( ORR ) of 60 percent .
Brad S . Kahl , MD , from the Washington University School of Medicine in St . Louis , Missouri , presented the interim results of this phase I trial in a standing-room-only session at the 2017 ASH Annual Meeting discussing new agents and upfront approaches in the treatment of aggressive lymphoma .
The study is recruiting a difficult-to-treat population , Dr . Kahl noted . Patients were either intolerant of previous therapy , had no other treatment options , or had had relapsed / refractory B-cell lineage NHL that did not respond to established therapies . As of November 1 , 2017 ( data cutoff ), 138 patients ( median age = 65.5 years ; range = 24-85 years ) were enrolled in the trial , including 85 patients with diffuse large B-cell lymphoma ( DLBCL ).
Patients received a median of three previous therapies ( range = 1-10 therapies ).
In the dose-escalation phase of the study , patients received a onehour infusion of loncastuximab tesirine at doses ranging from 15 to 200 µ g / kg for a median of two , three-week cycles ( range = 1-16 cycles ). One dose-limiting toxicity ( worsening of thrombocytopenia at the 200 µ g / kg dose ) was observed in one patient , but the maximum tolerated dose for the dose-expansion phase of the study had not yet been reached .
Nearly all patients experienced a treatment-related adverse event ( AE ; n = 135 ; 97.8 %), with 46 patients ( 57.5 %) experiencing a grade ≥3 treatment-related AE . The most common non-hematologic , all-grade AEs included fatigue ( n = 35 ; 43.8 %), peripheral edema ( n = 21 ; 26.3 %), and nausea ( n = 20 ; 25.0 %). Non-hematologic grade ≥3 AEs included
58 ASH Clinical News January 2018