The main evidence supporting the use of blinatumomab in minimal residual disease (MRD) positive disease derives from a phase 2, open label, multicentre study.r
To be eligible, patients were required to be in complete haematological remission (CHR), defined as <5% blasts, neutrophil count >1.0 x 109/L, platelets >50000/uL and Hb >9 g/dL. They were required to have molecular failure with persistent or recurrent MRD >10-3 and to have received 3 blocks of high-dose chemotherapy. Patients could be in their first or subsequent CHR.r
The main intention of the study was to determine the rates of conversion from MRD positivity to negativity and to assess what effect conversion to MRD negativity had on overall outcomes.r
Given that this population of patients is expected to have substantially lower disease burden, there was no ramp-up dosing in cycle 1, as there was in studies using blinatumomab in situations of frank relapsed or refractory disease. Corticosteroid pre-treatment was given before each cycle to reduce the risk of neurological events or cytokine release syndrome.r
Patients were given up to 4 cycles of blinatumomab but could proceed to haematopoietic stem cell transplantation at any time after cycle 1. The primary endpoint was rate of MRD response after cycle 1. The key secondary endpoint was haematological relapse-free survival (RFS) at 18 months after commencing blinatumomab.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Gokbuget et al. 2018r |
Yes |
Yes |
- |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
Acute lymphoblastic leukaemia V1.2018 |
Yes |
Yes |
- |
BCCA |
N/A |
N/A |
N/A |
- |
CCO |
March 2022 |
Yes |
Yes |
- |
Efficacy
113 patients were evaluable (59% male, 41% female). 88/113 (78%) achieved MRD negativity after cycle 1, 2 more patients after cycle 2, and then no further patients in cycle 3 or 4. In comparing MRD responders to non-responders; RFS was 23.6 vs 5.7 months and OS was 38.9 vs 12.5 months.
Patients had better response rates if they were in their first CHR, compared with later CHRs, with a median RFS of 24.6 vs 11.0 months respectively.r
Allogeneic transplantation
74/110 (67%) proceeded to allogeneic transplant. Of these, 36/74 (49%) were in CR at 2 years. This is compared with the 36/110 (33%) who did not proceed to allogeneic transplant, 9/36 (25%) were in CR at 2 years.r
Relapse-free survival by remission status at screening and responder statusr
© Blood 2018
Toxicity
The most common adverse reactions among adult patients were pyrexia (89%), headache (38%), tremor (30%), chills (25.9%), fatigue (24.1%), nausea (23.3%), vomiting (22.4%), hypokalaemia (15.5%), and diarrhoea (19.8%). The most common grade 3 to 4 toxicities were neutropenia (17.2%) and pyrexia (7.8%).r
Patients with grade 4 neurologic adverse events were required to permanently discontinue blinatumomab. 12/110 (10%) had >grade 3 neurologic adverse events and required treatment interruption. 7 were able to resume at a lower dose, of whom 5 were able to continue at this dose. The other 2 stopped therapy in view of another neurological event. Tremor (5 pts), aphasia (3), seizure (3) and encephalopathy (3) were the commonest neurological events requiring treatment cessation.r
Summary of adverse eventsr
© Blood 2018