Table 1.

Selected targeted therapies for Ph-negative BCP-ALL

ClassTargetCompoundStage of clinical development/activity in capsule
Unconjugated antibodiesCD20RituximabFDA approved for various CD20+ malignancies. Phase II trials in newly diagnosed adult CD20+ ALL demonstrate survival benefit in younger adults (45, 46). Phase III trial ongoing (GRALL-2005).
CD20OfatumumabOngoing phase II trial in newly diagnosed adult CD20+ ALL (47)a.
CD22EpratuzumabPhase II trials demonstrate the benefit of chemotherapy in combination with epratuzumab in pediatric and adult RR-ALL (48–50). Phase III trial ongoing for pediatric patients with relapsed ALL (NCT01802814).
CD52AlemtuzumabPostremission therapy in newly diagnosed adult ALL resulted in deeper MRD response in a phase I trial (51).a
ImmunoconjugatesCD22InotuzumabozogamicinSignificant single-agent activity in adults with RR-ALL (52); phase III ongoing and recently reported to have positive results in terms of CR rates (NCT01564784).
Ongoing early-phase trials of inotuzumab ozogamicin in combination with chemotherapy in the upfront or RR-ALL setting in adults (53, 54).a
CD19SGN19AOngoing phase I study in pediatric and adult patients with RR-ALL/lymphoma (55)a.
ImmunotoxinsCD22BL22/HA22Ongoing phase I trial in pediatric RR-ALL (56).a
CD22, CD19CombotoxPhase I trials in pediatric and adult RR-ALL completed (57, 58). Combotox in combination with cytarabine currently explored in adults.
T-cell engaging therapiesCD19BlinatumomabAccelerated FDA approval for Ph-negative RR-ALL based on phase II trials (31, 32). Effective in eradicating MRD (28–30).a Several phase II and III trials ongoing (e.g., NCT02003222, NCT02143414, NCT02013167, NCT02000427).
CD19CART cellsSignificant activity in pediatric and adult RR-ALL (40).
Kinase inhibitorsConstitutively activated kinases (Ph-like signature)Ruxolitinib, dasatinibPreclinical activity; anecdotal reports from the clinic (59).
  • aPresented in abstract form.