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. 2012 Jan 22;6:85–100. doi: 10.4137/CMO.S7262

Table 4.

Summary of emerging therapies in adult ALL.

Agent Mechanism Evidence in adult ALL Significant toxicity Current place in ALL therapy Future directions
Rituximab Anti CD20 monoclonal antibody Phase 2: Reduces relapse in CD20+ve ALL with a 3 yr CRD of 60% in under 60 year olds when used in combination with modified hyper CVAD17 Not licensed

  • Further assessment in 1st induction in CD20+ve ALL

  • Assess efficacy of 2nd generation monoclonal antibodies
Inotuzumab ozogamicin Immunotoxin: CD22 monoclonal antibody attached to calicheamycin Phase 2 (Early data): Promising as a single agent in relapsed, refractory B-ALL28, with CR in 56% and >60% proceeding to SCT29 Liver function abnormalities in 25%, severe in 11%28 Not licensed

  • Further assess efficacy in adult ALL

  • Further assessment of other immunotoxins eg, Combotox particularly in combination with cytotoxics
Blinatumomab Bispecific T cell engager Phase 2: In MRD persistence or relapse, 76% became MRD negative30 and early data suggesting efficacy in relapsed or refractory B-ALL (67% CR)32 Neurotoxicity: Seizures in 2/21 patients30 Not licensed

  • Further assess in MRD persistence or relapse

  • Consider use in 1st induction
Nelarabine Nucleoside Purine analogue Phase 2: 36% achieved CR in relapsed T-ALL39 Neurotoxicity. 16%, 7% grade 3–439 FDA approved for T-ALL/T-LBL failed 2 previous lines of therapy

  • Earlier use in adult T-ALL (1st relapse or 1st induction)

  • Combination regimens

  • Assess use as maintenance in patients ineligible for SCT

  • Further investigate other nucleoside purine analogues
Sorafenib Multi targeted tyrosine kinase inhibitor Phase 1: Limited so far86 Not licensed

  • Needs further assessment
Sirolimus mTOR inhibitor Phase 1: Limited response to monotherapy72 Not licensed

  • Assess combination regimes
Gamma secretase inhibitors NOTCH inhibitor MK-0752 Phase 1:Poor clinical response63 Gastro-intestinal toxicity Not licensed

  • Investigate combination regimes
Aurora kinase inhibitors Phase 1: Limited clinical response so far 89,91–93 MK-0457: QTc prolongation90 Not licensed

  • Further investigate use in Ph+ve leukemias

  • Combination regimes

  • Front line therapy with TKIs
Histone deacetylase inhibitors Limited clinical response so far but phase 1/2 trials ongoing106,107 Not licensed

  • Define efficacy as monotherapy

  • Optimal combination regimens
Decitabine DNA hypomethylating agent Phase 1: Efficacy as single agent (23% CR) or in combination with hyper CVAD (52% CR) at inducing short lived responses110 Not licensed

  • Assess long term outcome as single agent or in combination.

  • Investigate outcome of subsequent SCT
Mitoxantrone Topoisomerase inhibitor ALLR3 study: In pediatric patients, reduced relapse rate and increased OS at induction compared to idarubicin (3 yr OS 45% vs. 69%)113 Not licensed

  • Define efficacy in adult ALL

Abbreviations: ALL, acute lymphoblastic leukemia; CR, complete response; CRD, CR duration; LBL, lymphoblastic lymphoma; MRD, minimal residual disease; OS, overall survival; Ph+ve, Philadelphia chromosome positive; SCT, stem cell transplant.