Abstract 851P
Background
Adult relapsed or refractory acute lymphoblastic leukemia (RR ALL) is a rare and life-threatening disease if left untreated. Treatment of RR ALL is challenging because of chemo-resistance, toxicity of cytotoxic therapies, as well as high relapse rates. We aimed to identify published evidence for current therapies for adult RR ALL and review the efficacy.
Methods
Studies published between 2000-2020 were identified in MEDLINE and EMBASE, and stratified by treatment, study design (observational (Obs) or interventional (Int)), and treatment line (second line (2L) or post second line (2L+)). Efficacy data (overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), relapse-free survival (RFS), overall response rate (ORR)) were synthesized.
Results
Sixty-one studies were identified, including 22 Obs and 39 Int. The treatments included chemotherapy, blinatumomab, inotuzumab, tyrosine kinase inhibitor (TKI), stem-cell transplantation, and chimeric antigen receptor T-cell (CAR T) therapy. Most studies (n=34) include RR ALL patients with a mixed treatment line while four studies included only 2L patients and six included only 2L+ patients. Across different treatments, median PFS (or DFS/RFS) ranged 2.2 months–not reached in Int and 3.3-32.1 months in Obs; median OS in months ranged 3.4-25.0 in Int and 6.5-25.0 in Obs. Blinatumomab and inotuzumab showed better OS, PFS (or DFS/RFS), and ORR than chemotherapy and TKI (Table). Table: 851P
Range of median PFS (or DFS/RFS) and OS (in months) and ORR by selected treatments. N: number of studies
| By treatment | OS/Int (N) | OS/Obs (N) | PFS (or DFS/RFS)/Obs (N) | PFS (or DFS/RFS)/Obs (N) | ORR/Int (N) | ORR/Obs (N) |
| Blinatumomab | 6.1-9.8 (4) | 7.5-25.0 (3) | PFS: 5.9-7.6 (3) RFS: 6.7-not reached (2) | PFS: 3.3 (1) RFS: 32.1 (1) | 36%-44% (3) | 47%-69% (4) |
| Inotuzumab* | 7.7-25.0 (2) | 11.6 (1) | PFS: 5.0-11.0 (2) | - | 74%-92% (3) | 63%-82% (2) |
| Chemotherapy | 3.4-8.0 (7) | 6.5-7.6 (2) | PFS: 4.3-6.2 (3) DFS: 3.7-4.3 (2) | - | 14%-79% (5) | - |
| TKI | 3.6-9.0 (4) | 9.9 (1) | PFS: 2.2-3.0 (2) | DFS: 3.5 (1) | 9%-89% (5) | - |
*Including inotuzumab in combination with chemotherapy
Conclusions
This SLR identified both clinical trials and real-world studies of adult RR ALL treatments, with newer studies focused on immunotherapies such as blinatumomab and inotuzumab. Prognosis has improved with newer treatments, but the current SLR still shows a significant clinical unmet need in long term remission and survival for adult RR ALL.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vincent Lin, Autolus Therapeutics plc.
Funding
Autolus Therapeutics plc.
Disclosure
All authors have declared no conflicts of interest.