Efficacy
JULIET Study Design
JULIET was an open-label, multicenter, single-arm, global Phase II trial of tisagenlecleucel in 115 adult patients with DLBCL who have relapsed or are refractory to ≥2 prior lines of therapy (NCT02445248).1,2
JULIET Baseline Characteristics
PATIENT BASELINE CHARACTERISTICS WERE CONSISTENT ACROSS THE USPI AND UPDATED ANALYSES1-3,5
Patient Demographics (JULIET 9.4 month analysis, N=68)1
Aged 22-74 years (median, 56 years)
Progressive disease after autologous stem cell transplant (ASCT) or were ineligible for transplant (49% underwent ASCT)
Inclusion/Exclusion Criteria1,2
Histologically confirmed DLBCL (78% DLBCL not otherwise specified [NOS], 22% transformed follicular lymphoma [tFL])
≥2 prior lines of therapy (median, 3)
– 56% of patients had refractory disease and 44% relapsed after their last therapy
No prior anti-CD19 therapy or active central nervous system (CNS) involvement
End Points2
Primary: Best overall response rate (ORR) (complete response [CR] + partial response [PR])a
Key secondary: Duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety
Chemotherapy1
Bridging: 90% of patients
Lymphodepleting: 93% (107/115) of patients
– Recommended regimen: Fludarabine (25 mg/m2 intravenous [IV] daily for 3 days) and cyclophosphamide (250 mg/m2 IV daily for 3 days, starting with the first dose of fludarabine)
– Alternative regimen: Bendamustine 90 mg/m2 IV daily for 2 days
JULIET trial patient disposition1-3,6,7
EAS, efficacy analysis set; FAS, full analysis set; NEJM, New England Journal of Medicine; USPI, United States Prescribing Information.
aIndependent review committee (IRC) responses based on the Lugano Classification with a null hypothesis of ORR ≤20%.1
bAt the 32.6-month data cut, the enrollment was completed, and there were no infusions pending.3
cThe full analysis set and safety set were made up of all the patients who received an infusion, including those treated with KYMRIAH manufactured in the United States (main cohort) and in the European Union (cohort A) with a data cutoff date of July 1, 2019.3
dPatients in this data set either had no bridging chemotherapy or had imaging that showed measurable disease after completion of bridging chemotherapy and before KYMRIAH infusion.1
eThe first 92 patients who received KYMRIAH manufactured in the United States and completed at least 3 months’ follow-up or discontinued earlier.1
fPatients pending infusion at the time of data cutoff, September 6, 2017.7
gPatients were identified and excluded from the analysis because the treatment effect of KYMRIAH alone could not be determined.1
Overall Response Rate
KYMRIAH DELIVERS STRONG EFFICACY WITH DURABLE RESPONSES IN PATIENTS WITH R/R DLBCL1
Persistence based on pharmacokinetics1
In adult patients with r/r DLBCL who achieved a CR, KYMRIAH was present for up to 18 months in peripheral blood and 9 months in bone marrow.
Duration of Response
KYMRIAH IS A DURABLE TREATMENT WITH 60% OF PATIENTS STILL IN RESPONSE AT MONTH 40.37
The median duration of response has not been reached in both the overall and CR patient population in the 40.3-month analysis.7
hCR + PR.
iDOR was measured from date of first objective response to date of progression or death from relapse.1
JULIET 9.4-MONTH USPI ANALYSIS1
Median DOR was not reached. For patients who achieved a PR, median DOR was 3.4 months.
Progression-Free Survival
MORE THAN 60% OF PATIENTS WHO REACHED A CR AT MONTH 3 WITH KYMRIAH (n=37) WERE PROGRESSION-FREE AT 3 YEARS
PFS was a secondary efficacy end point of the JULIET trial, and is not included in the Prescribing Information.3 PFS data should be interpreted with caution in a single arm trial, as the statistical significance is unknown.
Median PFS was not reached for patients achieving complete response at Month 3 (n=37)6
Median PFS was 2.9 months (95% CI, 2.3–5.2) for all infused patients8
In a JULIET post hoc analysis, 38.2% of patients who received Flu/Cy (n=85) lymphodepleting chemotherapy were progression free at 2 years9
Alternate lymphodepleting chemotherapy (bendamustine 90mg/m2 IV daily for 2 days) was used if a patient experienced a previous grade 4 hemorrhagic cystitis or demonstrated resistance to a previous Cy-containing regimen10,k
j115 patients were infused with KYMRIAH (99 in the main cohort and 16 in cohort A), for this data cut n=115 patients.3,8
kEight patients in JULIET received no lymphodepleting chemotherapy.10
Overall Survival
MEDIAN OS WAS NOT REACHED FOR PATIENTS WITH A COMPLETE RESPONSE IN THE 40.3 MONTH ANALYSIS7
36% of all patients infused with KYMRIAH are still alive at 3 years.7
OS was a secondary end point of the JULIET trial and is not included in the Prescribing Information. OS data should be interpreted with caution in a single arm trial, as the statistical significance is unknown
Median time of survival from infusion was 11.1 months (95% CI: 6.64, 23.85) at 40.3 months (n=115) for all patients and not reached for patients in CR
l115 patients were infused with KYMRIAH (99 in the main cohort and 16 in cohort A); for this data cut n=115 patients.3
KYMRIAH DEMONSTRATED CONSISTENT RESPONSE RATES REGARDLESS OF CLINICAL CHARACTERISTICS2,7
KYMRIAH demonstrated consistent response rates across high-risk patient subgroups with non-Hodgkin lymphoma that have relapsed or are refractory after ≥2 lines of systemic therapy.2,7
HSCT, hematopoietic stem cell transplantation; NR, not reported.