On Location
Conference Coverage
ADVANCES ACROSS HEMATOLOGY
his month , we continue our coverage of the European Hematology Association ’ s 23rd Congress , which was held June 14-17 in Stockholm , Sweden , where more than 10,000 international hematologists met to share emerging results from clinical and translational research in hematologic disorders and discuss the latest evidence-based approaches to their diagnosis and management .
Here , ASH Clinical News presents highlights from the meeting , including IDH inhibitors in acute myeloid leukemia , nivolumab in newly diagnosed Hodgkin lymphoma , and more .
Attendees at the 23rd EHA Congress .
Updated Results from JULIET : Tisagenlecleucel Associated With Durable Responses in DLBCL
In May 2018 , the U . S . Food and Drug Administration expanded the approval of the chimeric antigen receptor ( CAR ) T-cell therapy tisagenlecleucel to the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ), based on results from the phase II JULIET trial . At the 23rd Congress of the European Hematology Association , Peter Borchmann , MD , of the University Hospital of Cologne in Germany , presented updated results on behalf of other investigators from the trial , which continued to show high response rates with tisagenlecleucel in this population .
“ Tisagenlecleucel was associated with a high rate of durable complete responses ,” Dr . Borchmann said . “ With longer follow-up , these results confirm findings of an earlier primary analysis .” The trial enrolled 165 adults with DLBCL who had been treated with at least two prior lines of therapy ( including rituximab and an anthracycline ) and who were eligible for or previously failed autologous hematopoietic cell transplantation ( AHCT ).
Patients were infused with a single dose of tisagenlecleucel ( median = 3.0 × 10 8 ; range = 0.1- 6.0 × 10 8 cells ). The CAR T-cell therapy was centrally manufactured via cryopreserved apheresis and a global supply chain .
A total of 111 patients ( median age = 56 years ; range = 22-76 years ) were successfully infused with tisagenlecleucel ; these patients comprised the safety analysis . Efficacy was assessed in patients with at least three months of follow-up ( n = 93 ) or earlier treatment discontinuation ( n = 81 ). Most patients
( 76 %) had stage III / IV disease at study entry , and the median number of prior lines of antineoplastic therapy was three ( range = 1-6 ). Ninety-three percent of patients had received lymphodepleting chemotherapy , and 92 percent received bridging therapy during the study .
After a median follow-up of 13.9 months postinfusion , the overall response rate ( ORR ) was 52 percent , which included a complete response rate of 40 percent and a partial response rate of 12 percent . Response rates were consistent across patient subgroups , the investigators noted , including patients with double-hit lymphoma and a history of AHCT .
The maximum follow-up for the efficacy population was 17.3 months , and although the median duration of response was not reached , the investigators estimated that the rate of 12-month relapsefree survival was 65 percent . The median overall survival ( OS ) among all 111 infused patients was 11.7 months ( range = 6.6 - not estimable ), and the estimated 12-month OS was 49 percent .
No participants proceeded to AHCT while in remission , the investigators noted . Tisagenlecleucel also appeared to be durable and was detected by polymerase chain reaction in the peripheral blood of responders for up to 693 days .
During the first eight weeks after infusion , patients experienced the following grade 3 / 4 adverse events ( AEs ):
• cytokine release syndrome ( 14 % [ grade 3 ] and 8 % [ grade 4 ])
• neurologic AEs , which were managed with supportive care ( 12 %)
• cytopenias lasting > 28 days ( 32 %)
• infections ( 20 %)
• febrile neutropenia ( 14 %)
Three participants died within 30 days of tisagenlecleucel infusion ; however , deaths were not considered related to the study drug or cytokine release syndrome . The investigators noted no new deaths for reasons other than disease progression since earlier reports from JULIET .
“ This is the first global study of CAR T-cell therapy in DLBCL to show that centralized manufacturing was feasible ,” Dr . Borchmann concluded . Future research should focus on better characterizing and predicting “ severe cytokine release syndrome and neurologic events ,” he added .
The findings from this study are limited by the small number of patients and the lack of a comparator arm .
REFERENCE Borchmann P , Tam CS , Jäger U , et al . An updated analysis of JULIET , a global pivotal phase 2 trial of tisagenlecleucel in adult patients with relapsed or refractory ( R / R ) diffuse large B-cell lymphoma ( DLBCL ). Abstract # S799 . Presented at the 23rd Congress of the European Hematology Association , June 16 , 2018 ; Stockholm , Sweden .
34 ASH Clinical News August 2018