Emerging treatments
OBI-3424
OBI-3424 is a highly selective prodrug that is converted by aldo-keto reductase family 1 member C3 (AKR1C3) to a potent DNA-alkylating agent.[162] AKR1C3 is upregulated in certain tumour cell types, but not expressed in normal healthy cells. OBI-3424 has received US Food and Drug Administration (FDA) designation as an orphan drug for the treatment of T-ALL. Clinical trials are ongoing.[163]
Revumenib
Revumenib, a menin inhibitor, has been granted breakthrough therapy designation by the FDA for the treatment of adult and paediatric patients with relapsed/refractory (R/R) leukaemia harbouring a KMT2A rearrangement. One phase 2 study of revumenib in infants and young children with R/R KMT2A-rearranged leukaemia, in combination with chemotherapy, is scheduled to begin in 2023.[164]
Blinatumomab (front-line therapy)
Blinatumomab is being investigated as front-line therapy in combination with a tyrosine kinase inhibitor (TKI) in patients with newly diagnosed Philadelphia chromosome-positive (Ph+) ALL and as sequential chemotherapy (hyper-CVAD) in newly diagnosed Ph-negative B-cell ALL.[165][166]
Inotuzumab ozogamicin plus TKI (for relapsed or refractory Ph+ ALL)
In a phase 1/2 trial, inotuzumab ozogamicin with bosutinib resulted in an objective response rate of 81% in 18 patients (16 patients with relapsed-refractory Ph+ B-ALL and 2 with chronic myeloid leukaemia in lymphoid blast phase).[167]
Inotuzumab ozogamicin (for older patients with newly diagnosed Ph-negative ALL)
Inotuzumab ozogamicin (with or without blinatumomab) added to low-intensity chemotherapy showed promising activity in a phase 2 trial of older patients with B-cell acute lymphocytic leukaemia.[168]
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