Clinical trialPhase 3Blood cancers (leukaemia, lymphoma and myeloma)Leukaemia

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults

N Engl J Med · 2024488 patients enrolled; 224 MRD-negative patients were randomised (112 per group)

Litzow MR, Sun Z, Mattison RJ, et al. N Engl J Med. 2024. 391:320-333

Study type: Clinical trial
Study name: E1910
Phase: Phase 3
Design: Randomised, open-label trial, ECOG-ACRIN cooperative group (funded by the US National Institutes of Health)
Sample size: 488 patients enrolled; 224 MRD-negative patients were randomised (112 per group)
Source: N Engl J Med · 2024
Trial registration: NCT02003222

In plain words

Even when very sensitive tests show no trace of acute lymphoblastic leukaemia (MRD-negative), many adults relapse. This study showed that adding blinatumomab — a drug that steers the patient's own immune cells towards the leukaemia cells — to consolidation chemotherapy cuts the risk of death by more than half. The drug is given by a pump as a continuous infusion and can cause nervous system side effects such as tremor, confusion or speech problems, which usually go away when the drug is paused.

Key results

85% vs 68%

3-year overall survival

HR for death 0.41 (95% CI 0.23–0.73); P=0.002; median follow-up 43 months

80% vs 64%

3-year relapse-free survival

HR for relapse or death 0.53 (95% CI 0.32–0.87)

Dose and schedule cards

Blinatumomab in consolidation (E1910)

Philadelphia-negative CD19-positive B-ALL in the consolidation phase of multiphase chemotherapy; in E1910, adults aged 30 to 70 years in MRD-negative CR or CRiCycle length: Every 42 daysOn the page “Leukaemia” · Regimens and dosing in Philadelphia-negative ALL

Philadelphia-negative CD19-positive B-ALL in the consolidation phase of multiphase chemotherapy; in E1910, adults aged 30 to 70 years in MRD-negative CR or CRi

Drug	Dose	Route	Schedule
Each blinatumomab cycle
Blinatumomab	45 kg or more: 28 mcg per day; less than 45 kg: 15 mcg/m² per day (maximum 28 mcg per day)	IV, continuous infusion by pump	Days 1–28, then 14 days off

Cycle length: Every 42 days
Duration: In E1910: 2 blinatumomab cycles → 3 cycles of consolidation chemotherapy → third blinatumomab cycle → fourth chemotherapy cycle → fourth blinatumomab cycle; then maintenance until 2.5 years from the start of intensification

Premedication: dexamethasone 20 mg IV within 1 hour before the first dose of each cycle. Hospitalisation is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. Intrathecal prophylaxis before and during treatment. Other label schedules: MRD-positive ALL (≥0.1%): 28 mcg per day, 1 induction cycle + up to 3 consolidation cycles (premedication with prednisone 100 mg IV); relapsed or refractory ALL: first cycle 9 mcg per day on Days 1–7 and 28 mcg per day on Days 8–28, then 28 mcg per day for up to 2 induction cycles, 3 consolidation cycles and up to 4 continued-therapy cycles (28 days of infusion + 56 days off), with hospitalisation for the first 9 days.

On the page “Leukaemia” · Regimens and dosing in Philadelphia-negative ALL

Blinatumomab in ALL

CD19-positive B-ALL: Ph-negative consolidation (E1910) or relapsed/refractory (TOWER)On the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in leukaemias

CD19-positive B-ALL: Ph-negative consolidation (E1910) or relapsed/refractory (TOWER)

Drug	Dose	Route	Schedule
Consolidation (E1910)
Blinatumomab	45 kg or more: 28 mcg/day (less than 45 kg: 15 mcg/m²/day)	IV, continuous infusion	Days 1–28, then 14 days off
Relapsed/refractory, Cycle 1
Blinatumomab	9 mcg/day, then 28 mcg/day	IV, continuous infusion	Days 1–7, then Days 8–28
Relapsed/refractory, subsequent cycles
Blinatumomab	28 mcg/day	IV, continuous infusion	Days 1–28

Cycle length: Every 42 days (continued therapy cycles in relapse: every 84 days)
Duration: E1910: 4 cycles of blinatumomab interspersed with consolidation chemotherapy; relapse: up to 2 induction cycles, 3 consolidation cycles and 4 continued therapy cycles

Premedication with dexamethasone 20 mg before the first dose of each cycle, intrathecal prophylaxis, and hospitalisation during the first days (relapse: first 9 days of Cycle 1); boxed warning for cytokine release syndrome and neurological toxicity.

On the page “Blood cancers (leukaemia, lymphoma and myeloma)” · Treatment regimens and dosing in leukaemias

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Blinatumomab + consolidation chemotherapy

Blinatumomab 28 µg per day as a continuous IV infusion for 4 weeks, with 2 weeks between cycles (42-day cycle); a total of 4 blinatumomab cycles interspersed with 4 consolidation chemotherapy cycles (per the FDA label: 2 blinatumomab cycles → 3 chemotherapy cycles → third blinatumomab cycle → fourth chemotherapy cycle → fourth blinatumomab cycle). Patients who did not undergo transplantation continued maintenance for up to 2.5 years from the start of intensification.

Chemotherapy backbone based on UKALL XII/E2993 with paediatric-like modifications (lower daunorubicin dose, pegaspargase instead of E. coli asparaginase, dexamethasone instead of prednisone); the intensification phase included high-dose IV methotrexate and pegaspargase. Per the label: premedication with dexamethasone 20 mg IV before the first dose of each cycle, hospitalisation for the first 3 days of cycle 1 and the first 2 days of cycle 2, and intrathecal prophylaxis. Chemotherapy dosing details in the paper's protocol.

2Consolidation chemotherapy alone

The same 4 consolidation chemotherapy cycles followed by maintenance for up to 2.5 years from the start of intensification; dosing details in the paper's protocol.

Source of the regimen details: Full text of the paper in PMC (PMC11334054), Methods section, and the FDA label for blinatumomab (DailyMed; section 14.3 cycle sequence, premedication and hospitalisation)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults aged 30 to 70 years with BCR::ABL1-negative B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) who, after induction and intensification chemotherapy, were in remission with negative measurable residual disease (MRD) (less than 0.01% leukaemic cells in the bone marrow by flow cytometry).

Endpoints

Primary endpoint: overall survival.

Secondary endpoint: relapse-free survival.

Safety and side effects

Neuropsychiatric events were more frequent in the blinatumomab group: treatment-related grade 3 or higher neurological or psychiatric adverse events in 23% of the blinatumomab group versus 5% of the chemotherapy group (P<0.001; full text).

Clinical significance and place in guidelines

Based on this study, in June 2024 the FDA approved blinatumomab for consolidation treatment of CD19-positive, Philadelphia chromosome-negative BCP-ALL in adults and children aged one month and older, regardless of MRD status. Adding blinatumomab to consolidation in adults with Philadelphia-negative ALL has now become the standard of care.

Limitations

The study was open-label (unblinded), and results were reported from an interim analysis. Patients younger than 30 or older than 70 years and those with Philadelphia-positive ALL were not enrolled. The backbone chemotherapy regimen (similar to E2993) differs from the paediatric-inspired regimens now used in young adults.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.