1. ELIANA: CTL019 Shows High CR Rate in Pediatric/Young Adult Patients With Relapsed/Refractory B-Cell ALL
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
ALL, acute lymphoblastic leukemia.
This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. ELIANA: Background
CTL019: modified T-cell therapy produced with CD19-specific chimeric antigen receptors
Earlier single-site phase I/IIA trial in pediatric and young adult pts with R/R B-cell ALL showed promise of CTL019[1]
93% (55/59) achieved CR at Day 28 with prolonged CTL019 persistence
This phase II study is the first global pivotal registration trial for CAR T-cell therapy and was designed to evaluate single infusion of CTL019 in pts 3-21 yrs of age with R/R B-cell ALL[2]
ALL, acute lymphoblastic leukemia; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
1. Grupp SA, et al. ASH Abstract Grupp SA, et al. ASH Abstract 221.

3. ELIANA: Study Design
Multicenter, open-label, single-arm phase II study
Primary endpoint: ORR (CR + CRi) within 3 mos, assessed by IRC
4-wk maintenance of remission required
Secondary endpoints: MRD status, DoR, OS, cellular kinetics, safety
Pts aged 3-21 yrs* with B-cell ALL; ≥ 5% BM lymphoblasts; no isolated extramedullary disease relapse, prior CD19-directed therapy, or prior gene therapy
(N = 81)
Fludarabine
30 mg/m² IV QD for 4 doses
Cyclophosphamide
500 mg/m² IV QD for 2 doses
Single-Dose CTL019
x 106/kg IV if ≤ 50 kg
x 108 IV if > 50 kg
(n = 62†)
†14 pts discontinued before infusion: deaths (n = 6), manufacturing failures (n = 5), AEs (n = 3).
*From 3 yrs at screening to 21 yrs at initial diagnosis.
ALL, acute lymphoblastic leukemia; BM, bone marrow; CRi, CR with incomplete hematologic recovery; DoR, duration of response; IRC, independent review committee; MRD, minimal residual disease.
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

4. ELIANA: Baseline Characteristics
CTL019 (N = 62)
Median age, yrs (range)
12 (3-23)
Male, % 55
Previous stem cell transplant, % 56
Median previous lines of therapy, n (range)
3 (1-8)
Current disease status, %
Primary refractory
Chemotherapy refractory
Relapsed 10 11 79
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

5. ELIANA: Efficacy
Outcome
CTL019 (n = 50*)
ORR (CR + CRi) within 3 mos (with MRD < 0.01% in BM), % (95% CI)
82 (69-91)†
Best overall response, % CR
CRi 68 14 OS
6 mos, % (95% CI)
Median, mos (95% CI)
89 (76-95)‡
NE (8.6-NE)‡
Duration of remission
62 (36-78)
NE (4.8-NE)
AUC, area under the curve; BM, bone marrow; CRi, CR with incomplete hematologic recovery; MRD, minimal residual disease; ORR, overall response rate.
*Interim analysis set: first 50 pts infused with CTL019 with 3-mo follow-up. †P < ‡Full analysis set: all pts infused with CTL019.
Pts with CR/CRi achieved higher Cmax and AUC0-28d, earlier max expansion of CTL019 cells vs nonresponders (Day 10 vs Day 27)
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

6. ELIANA: Adverse Events
Most AEs occurred in first 8 wks after CTL019 infusion
Deaths within 30 days of CTL019 infusion: ALL, cerebral hemorrhage, each n = 1
No deaths due to cytokine release syndrome
No reported cases of cerebral edema
Event, %
≤ 8 Wks After Infusion
(N = 62)
> 8 Wks After Infusion
(n = 52)
Serious AE
CTL019 related* 71 68 17 2
Grade 3/4 AE 86 74 31 10
AEs, adverse events; ALL, acute lymphoblastic leukemia.
*Suspected.
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

7. ELIANA: Adverse Events
Select AEs, %
CTL019 (N = 62)
Any Grade
Grade 3
Grade 4
CRS* 79 21 27
Transient neuropsychiatric event* 45 15
Infection* 40 23 3
Decreased appetite 39 2
Pyrexia 37 13
Cytopenia not resolved by Day 28* 11 19
Hypotension 33
AST increase 31 5
Hypokalemia 26
Hypoxia 6
Tumor lysis syndrome*
AEs, adverse events; AST, aspartate aminotransferase; CRS, cytokine release syndrome.
*Of special interest and occurring during the 8 wks after CTL019 infusion.
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

8. ELIANA: Cytokine Release Syndrome
Outcome
Infused Pts With CRS (n = 49)
Median time of onset, days (range)
3 (1-22)
Median duration, days (range)
8 (1-36)
Admitted to ICU,* %
Median duration of ICU stay, days (range) 59
8 (1-34)
Therapy, %
Anticytokine therapy
High-dose vasopressors
Invasive ventilation
Dialysis 51 33 20 12
CRS, cytokine release syndrome; ICU, intensive care unit.
*ICU admission in all pts, n/N (%): 29/62 (46.8).
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

9. ELIANA: Conclusions
In a worldwide trial of pediatric and young adult pts with R/R B-cell ALL, single, weight-based infusion of CTL019 met primary endpoint with CR/CRi of 82%
Durable CRs were observed
All CRs were MRD negative
Cytokine release syndrome managed with therapy, no CRS-related deaths observed
Overall safety findings consistent with previous CTL019 experience
Study investigators suggest that CTL019 may offer new option for this pt population
ALL, acute lymphoblastic leukemia; CRi, CR with incomplete hematologic recovery; CRS, cytokine release syndrome; MRD, minimal residual disease; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Grupp SA, et al. ASH Abstract 221.

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