What changed: Acute lymphoblastic leukaemia

When this page itself was last checked or edited.

Paediatric-inspired regimens (CALGB 10403, GRAALL, UKALL) with asparaginase; blinatumomab consolidation (E1910); MRD-guided transplant. (NCCN Category 1 (blinatumomab consolidation))

Hyper-CVAD or age-adapted multi-agent chemotherapy with blinatumomab interleaved in consolidation (E1910); inotuzumab-containing lower-intensity regimens (Mini-hyper-CVD + InO ± blinatumomab) for older adults; MRD-driven transplant. (NCCN Category 1 (E1910 regimen))

Blinatumomab (BLAST; full approval 2018) to convert to MRD negativity, then transplant or continued blinatumomab-based therapy. (NCCN Category 1)

Ponatinib (PhALLCON) or dasatinib with reduced-intensity chemotherapy, or chemotherapy-free TKI + blinatumomab (D-ALBA); BCR::ABL1 PCR monitoring; transplant for MRD persistence or IKZF1-plus, increasingly omitted for MRD-negative patients. (NCCN Category 2A (ponatinib preferred TKI))

Blinatumomab (TOWER) or inotuzumab (INO-VATE) as salvage and bridge; CD19 CAR-T (tisagenlecleucel ≤25 years; obe-cel or brexucabtagene in adults) for second salvage or as definitive therapy; transplant for those not previously transplanted; CD22 or dual CAR-T for CD19-negative relapse in trials. (NCCN Category 2A)

Intensive paediatric-type chemotherapy with nelarabine for high-risk (AALL0434); relapse: nelarabine, venetoclax combinations, CD7 CAR-T and daratumumab in trials; transplant in CR2. (NCCN Category 2A)

Intensified chemotherapy; blinatumomab for MRD persistence (AALL1331 in relapse); inotuzumab and CAR-T (tisagenlecleucel) for relapse; allogeneic transplant for very high risk or MRD persistence. (NCCN Category 2A)

Risk-adapted multi-agent chemotherapy (induction, consolidation, interim maintenance, delayed intensification, 2-3 years maintenance) with two cycles of blinatumomab in consolidation (AALL1731, approved June 2024); intrathecal CNS prophylaxis; cranial radiation abandoned for most. (NCCN Category 1 (blinatumomab in consolidation))

Interfant-21 backbone with blinatumomab; transplant for high-risk; menin inhibitors in trials. (NCCN Clinical trial preferred)

Subcutaneous blinatumomab trials (including the first in mixed-phenotype leukaemia) aim to replace continuous infusion; infant trials integrate blinatumomab.

Relapsed or refractory B-ALL, adults ≥26 years

ORR 73% (37 of 51) in relapsed or refractory B-cell malignancies; two treatment-related deaths.

FDA lifts REMS for approved CAR-T products; ziftomenib and revumenib studied in KMT2Ar ALL.

FELIX; approved without REMS

Relapsed or refractory B-cell precursor ALL, adults

CR+CRh 22.

3-year DFS 96.

3-year OS 85% vs 68%; HR 0.

ORR 77%, CR 55%; grade ≥3 CRS 2.

MRD-negative CR 34.

A milestone in how this cancer is treated.

Immunotherapy becomes part of standard first-line therapy for adults and children; second CAR-T for adult ALL; revumenib approved for KMT2Ar leukaemia.

Adult relapsed or refractory CD19-positive B-cell acute lymphoblastic leukaemia

Relapsed or refractory B-cell lymphoma and B-cell acute lymphoblastic leukaemia

Confirmed: the accelerated approval of 2004 converted to traditional approval 17.6 years after it was granted.

Bortezomib did not significantly improve four-year event-free survival for the whole group (83.

Blinatumomab consolidation gave two-year disease-free survival of 54.

Nelarabine improved disease-free survival in T-cell acute lymphoblastic leukaemia, and Capizzi methotrexate outperformed high-dose methotrexate.

18-month OS 95%, DFS 88%.

Dasatinib then blinatumomab, 18-month OS 95%.

6-year EFS 46.

MRD in bone marrow, B-cell acute lymphoblastic leukaemia and multiple myeloma (De Novo)

ORR 81%; 12-month OS 76%; 5-year OS 55%.

Imatinib with BFM chemotherapy gave four-year disease-free survival of 72.

Hyperfractionated cyclophosphamide did not improve remission, event-free or overall survival; five-year event-free survival was 52.

First approval based on an MRD endpoint (BLAST).

OS 7.

ELIANA-based approval for ALL up to age 25; TOWER OS 7.7 vs 4.0 months.

A milestone in how this cancer is treated.

Five-year event-free survival 79.

15-year all-cause mortality among five-year survivors fell from 12.

CR/CRi 80.

CR/CRi 81% vs 29%; approval 2017.

Oral suspension for ALL maintenance (Purixan)

Accelerated approval in relapsed/refractory Ph-negative B-ALL.

A milestone in how this cancer is treated.

ALL in adults, adolescents and children (Xaluprine oral suspension)

CTL019 at CHOP/Penn; durable remission of refractory paediatric ALL.

Three-year progression-free survival 64.

AIEOP-BFM 2000 and UKALL 2003 show end-of-induction MRD outperforms every clinical factor; MRD-directed therapy adopted.

Relapsed or refractory ALL in children after at least two prior regimens (Evoltra)

Accelerated approval on a surrogate endpoint, with a confirmatory trial required.

Relapsed or refractory ALL in patients aged 1 to 21 after at least two prior regimens (accelerated)

First BCR::ABL1 inhibitor; Ph+ ALL survival doubles when added to chemotherapy.

Refractory childhood acute lymphoblastic leukaemia, in combination induction

NCI/Rome criteria (age, white count); paediatric cooperative groups reach ~70% cure.

Pinkel's 'total therapy' at St. Jude: multi-agent induction, cranial irradiation, maintenance; first cures.

Acute lymphoblastic leukaemia, combination maintenance therapy

Aminopterin in children with ALL; the birth of cancer chemotherapy.

A milestone in how this cancer is treated.