The evidence for tisagenlecleucel treatment of relapsed or refractory B-cell ALL is based on the ELIANA studyr, a single-cohort, phase 2, multicenter, global study of tisagenlecleucel in children and young adults (age 3-21 at diagnosis) with relapsed or refractory B-cell ALL, with at least 5% lymphoblasts in bone marrow at screening.r
In the study, 75 patients received an infusion of tisagenlecleucel, median age 11 years (range, 3 to 23), with a median of 3 previous therapies (range, 1 to 8), and a median marrow blast percentage of 74% (range, 5 to 99). 46 patients (61%) had undergone previous allogeneic haematopoietic stem cell transplantation (HSCT).r
Before tisagenlecleucel infusion, 72 of 75 patients (96%) received lymphodepleting chemotherapy (omitted at investigator discretion due to leukopenia) consisting of fludarabine 30 mg/m2 for 4 days and cyclophosphamide 500 mg/m2 for 2 days [71 patients; or equivalent child dose] or one patient received cytarabine–etoposide.r Patients received a median weight-adjusted dose of 3.1×106 transduced viable T-cells/kg (range, 0.2×106 to 5.4×106 cells/kg); the median total dose of transduced viable T-cells was 1.0×108 (range, 0.03×108 to 2.6×108 cells).r
The primary endpoint was overall remission rate within 3 months of treatment.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trial |
Maude et al.r2018 |
Yes |
Yes |
- |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
Acute lymphoblastic leukemia v3.2023 |
Yes |
Yes |
- |
BCCA |
N/A |
N/A |
N/A |
- |
CCO |
N/A |
N/A |
N/A |
- |
ESMO |
N/A |
N/A |
N/A |
- |
Efficacy
The overall remission rate was 81% (95% CI, 71 to 89), 60% had complete remission (CR), while 21% had complete remission with incomplete haematologic recovery (CRi). All patients who had a best overall response (BOR; no clinical evidence of relapse more than 4 weeks after the initial CR or CRi) were negative for minimal residual disease (MRD), 95% (58 of 61) of these patients were negative by day 28.r
The event-free survival (EFS) was 73% (95% CI, 60 to 82) at 6 months and 50% (95% CI, 35 to 64) at 12 months. Eight patients underwent allogeneic HSCT while in remission, including 2 patients with MRD-positive bone marrow and 2 with B-cell recovery within 6 months after infusion. Overall survival (OS) among the 75 patients who received tisagenlecleucel was 90% (95% CI, 81 to 95) at 6 months and 76% (95% CI, 63 to 86) at 12 months after infusion.r
Figure 1: Event-free and overall survival with tisagenlecleucel
© NEJM 2018
Toxicity
66 of 75 patients (88%) had a Grade 3 or 4 adverse event, with the most clinically significant being:
- Cytokine release syndrome (CRS; graded according to the Penn Grading Scale for CRS) occurred in 77% (Grade 3 or 4 in 46%), the median time to onset was 3 days (range, 1 to 22), and the median duration was 8 days (range, 1 to 36)
- Neurologic events (graded by CTCAE v. 4.03) occurred in 30 of 75 patients (40%), Grade 3 in 13%, no Grade 4 events. Majority of neurological events occurred during the CRS or shortly after its resolution
- Cytopenias not resolved by day 28 occurred in 37% of patients, with 16% Grade 3 and 16% Grade 4 events
- Infections in the first 8 weeks occurred in 43%, 21% Grade 3 and 3% Grade 4
- Tumour lysis syndrome was only seen in 4%.
Majority of adverse events occurred within the first 8 weeks after infusion with 52 of 75 patients (69%) experiencing a Grade 3 or 4 tisagenlecleucel-related adverse event compared with 12 out of 70 patients (17%) from 8 weeks to 1 year post-infusion.
Table 1: Adverse event of special interest within 8 weeks of tisagenlecleucel infusion
© NEJM 2018