Selection of drugs used in the treatment of adults with ALL and the characteristics that make them challenging to administer
| Drug name (and class) . | NCCN recommended use . | FDA-approved indications . | Unique challenges with delivery . |
|---|---|---|---|
| Blin (BiTE) | Combined with TKI for Ph+ B-ALL R/R B-ALL Consolidation after chemotherapy for Ph– B-ALL | Consolidation after chemotherapy for Ph– B-ALL MRD+ B-ALL R/R B-ALL | High cost Administered via 28-d continuous IV infusion Idiosyncratic side-effect profile |
| Brexu-cel, obe-cel, and tisa-cel (CAR-T) | R/R B-ALL∗ | R/R B-ALL∗ | High cost Available only at certified sites Complexities of cell collection and manufacturing Idiosyncratic side-effect profile |
| InO (ADC) | Induction therapy of B-ALL aged ≥65 years Combined with mini-hyperCVD for newly diagnosed or R/R B-ALL R/R B-ALL (including with TKI for Ph+ ALL) | R/R B-ALL | High cost |
| Nelarabine (antimetabolite) | Combined with multiagent chemotherapy for newly diagnosed T-ALL R/R T-ALL | T-ALL that has not responded to or relapsed after 2 prior chemotherapy regimens | High cost Very rare indication |
| Pegaspargase (asparaginase) | Combined with multiagent chemotherapy for newly diagnosed and R/R Ph– ALL Combined with multiagent chemotherapy for R/R Ph+ ALL refractory to TKI | Combination with multiagent chemotherapy for newly diagnosed ALL | High cost Idiosyncratic side-effect profile Limited shelf life |
| Ponatinib (TKI) | Combined with blin, chemotherapy, or corticosteroid for newly diagnosed Ph+ B-ALL Single agent or combined with blin or InO for R/R Ph+ ALL | Combined with chemotherapy for newly diagnosed Ph+ ALL T315I mutated Ph+ ALL or if no other TKIs are indicated | Copay considerations for prescription coverage May only be available through specialty mail-order pharmacy |
| Recombinant Erwinia asparaginase (asparaginase) | Substitution for pegaspargase after hypersensitivity reaction as part of multiagent chemotherapy regimen | Part of multiagent chemotherapy regimen after hypersensitivity to Escherichia coli–derived asparaginase | High cost Idiosyncratic side-effect profile Very rare indication |
| Drug name (and class) . | NCCN recommended use . | FDA-approved indications . | Unique challenges with delivery . |
|---|---|---|---|
| Blin (BiTE) | Combined with TKI for Ph+ B-ALL R/R B-ALL Consolidation after chemotherapy for Ph– B-ALL | Consolidation after chemotherapy for Ph– B-ALL MRD+ B-ALL R/R B-ALL | High cost Administered via 28-d continuous IV infusion Idiosyncratic side-effect profile |
| Brexu-cel, obe-cel, and tisa-cel (CAR-T) | R/R B-ALL∗ | R/R B-ALL∗ | High cost Available only at certified sites Complexities of cell collection and manufacturing Idiosyncratic side-effect profile |
| InO (ADC) | Induction therapy of B-ALL aged ≥65 years Combined with mini-hyperCVD for newly diagnosed or R/R B-ALL R/R B-ALL (including with TKI for Ph+ ALL) | R/R B-ALL | High cost |
| Nelarabine (antimetabolite) | Combined with multiagent chemotherapy for newly diagnosed T-ALL R/R T-ALL | T-ALL that has not responded to or relapsed after 2 prior chemotherapy regimens | High cost Very rare indication |
| Pegaspargase (asparaginase) | Combined with multiagent chemotherapy for newly diagnosed and R/R Ph– ALL Combined with multiagent chemotherapy for R/R Ph+ ALL refractory to TKI | Combination with multiagent chemotherapy for newly diagnosed ALL | High cost Idiosyncratic side-effect profile Limited shelf life |
| Ponatinib (TKI) | Combined with blin, chemotherapy, or corticosteroid for newly diagnosed Ph+ B-ALL Single agent or combined with blin or InO for R/R Ph+ ALL | Combined with chemotherapy for newly diagnosed Ph+ ALL T315I mutated Ph+ ALL or if no other TKIs are indicated | Copay considerations for prescription coverage May only be available through specialty mail-order pharmacy |
| Recombinant Erwinia asparaginase (asparaginase) | Substitution for pegaspargase after hypersensitivity reaction as part of multiagent chemotherapy regimen | Part of multiagent chemotherapy regimen after hypersensitivity to Escherichia coli–derived asparaginase | High cost Idiosyncratic side-effect profile Very rare indication |
Drugs are listed in alphabetical order by generic name. All uses are as single agents unless designated as combinations.
ADC, antibody-drug conjugate; blin, blinatumomab; BiTE, bispecific T-cell engager; brexu-cel, brexucabtagene autoleucel; CAR-T, chimeric antigen receptor–modified T-cell therapy; FDA, US Food and Drug Administration; InO, inotuzumab ozogamicin; obe-cel, obecabtagene autoleucel; MRD, measurable/minimal residual disease; R/R, relapsed or refractory; tisa-cel, tisagenlecleucel; TKI, tyrosine kinase inhibitor.
For tisa-cel only, the NCCN recommendation and FDA approval include these qualifications: age <26 years with either refractory disease or second or greater relapse.