Comparison between blinatumomab and CD19CAR T-cell therapy
| . | Blinatumomab . | CD19CAR T cell . |
|---|---|---|
| FDA age approval | No age limit | Only for patients ≤25 y old |
| Indication | Any relapse or refractory B-cell ALL, including r/r MRD+ disease | Primary refractory or relapse disease with failure to respond to at least 2 lines of prior anti-ALL therapies |
| Availability | Immediate, off-the-shelf product and not patient specific | Require manufacturing |
| Favorable choice for proliferative ALL cases that need immediate intervention | Not suitable for cases that cannot wait for the duration of manufacturing or unlikely to be able to undergo leukapheresis due to high leukemia burden or low lymphocyte count | |
| Method of administration | Continuous IV infusion for 28 d of every 42-d cycle | Single IV infusion |
| Lymphodepletion | Not required; however, cytoreduction can potentially improve response in patients with high leukemia burden | This is usually required |
| Efficacy in r/r (≥5% blasts) | Response appears lower (CR/CRh = 36% to 69%) compared with CD19CAR T cell | Response appears higher (CR/CRi = 67% to 93%) than blinatumomab |
| Efficacy in MRD+ (<5% blasts) | Very high (∼80%), and outcomes are encouraging in patients who are treated in CR1 compared with MRD+ beyond CR1 | Response appears high; however, no study specifically was designed for MRD |
| Small Chinese study (N = 9) showed all MRD+ ALL achieved MRD− posttreatment | ||
| Efficacy in EMD | EMD confers lower response, and it is a frequent site for relapse | Preliminary data appear promising, with no adverse impact on response |
| Not a favorable choice | A better choice in ALL with EMD | |
| CNS involvement | No data available, and this was an exclusion criterion from published studies | CD19CAR T cells are detected in the CSF |
| It is better to avoid in patients with active CNS involvement | Promising responses are observed in cases with at least low level of CNS involvement | |
| Activity in older adults | Age has no impact on response | Limited data regarding activity but promising high response rate was observed |
| Activity in post–allo-HCT relapse setting | Response is comparable | Response is comparable |
| Impact of ALL genetic on activity | No impact of genetics on response | High activity regardless of genetics |
| High response in Ph-like ALL66 | One study correlated TP53 mutation with lower response27 | |
| The impact of high disease burden | High disease burden is associated with lower activity and higher toxicity | The impact of disease burden on response is mixed, however, OS and EFS appears lower in 1 study |
| High disease burden is associated with higher toxicity | ||
| CD19− relapse after initial response* | Of reported studies, 15 of 53 relapses (28%) following blinatumomab were CD19− | Of the reported studies, 33 of 83 relapses (40%) following CD19CAR were CD19− |
| Induction of GVHD in post–allo-HCT setting | Uncommon (11%), and the majority were low grade | Rare (none to only few cases with low grade in reported studies) |
| Severe CRS | Less common (0% to 6%) | It is more common (23% to 47%) |
| Severe neurotoxicity (≥3) | Less common (9% to 13%), more frequently in elderly (28% vs 13%), reversible and usually short-lived | More common (13% to 50%), usually reversible but lasts for longer duration (median ∼10 d) |
| Sequence of therapy | Limited data on the activity of blinatumomab after CD19CAR | No impact of prior history of blinatumomab on CD19CAR T activity, as long as CD19 expression is retained |
| Consolidation with allo-HCT | Data support consolidation with allo-HCT in r/r ALL | Durable remission is observed following CD19CAR (U Penn and MSKCC) but not with the NCI or the Chinese CD19CAR |
| Preliminary data are encouraging in blinatumomab administered for MRD+ ALL in which durable remission without allo-HCT was observed |
| . | Blinatumomab . | CD19CAR T cell . |
|---|---|---|
| FDA age approval | No age limit | Only for patients ≤25 y old |
| Indication | Any relapse or refractory B-cell ALL, including r/r MRD+ disease | Primary refractory or relapse disease with failure to respond to at least 2 lines of prior anti-ALL therapies |
| Availability | Immediate, off-the-shelf product and not patient specific | Require manufacturing |
| Favorable choice for proliferative ALL cases that need immediate intervention | Not suitable for cases that cannot wait for the duration of manufacturing or unlikely to be able to undergo leukapheresis due to high leukemia burden or low lymphocyte count | |
| Method of administration | Continuous IV infusion for 28 d of every 42-d cycle | Single IV infusion |
| Lymphodepletion | Not required; however, cytoreduction can potentially improve response in patients with high leukemia burden | This is usually required |
| Efficacy in r/r (≥5% blasts) | Response appears lower (CR/CRh = 36% to 69%) compared with CD19CAR T cell | Response appears higher (CR/CRi = 67% to 93%) than blinatumomab |
| Efficacy in MRD+ (<5% blasts) | Very high (∼80%), and outcomes are encouraging in patients who are treated in CR1 compared with MRD+ beyond CR1 | Response appears high; however, no study specifically was designed for MRD |
| Small Chinese study (N = 9) showed all MRD+ ALL achieved MRD− posttreatment | ||
| Efficacy in EMD | EMD confers lower response, and it is a frequent site for relapse | Preliminary data appear promising, with no adverse impact on response |
| Not a favorable choice | A better choice in ALL with EMD | |
| CNS involvement | No data available, and this was an exclusion criterion from published studies | CD19CAR T cells are detected in the CSF |
| It is better to avoid in patients with active CNS involvement | Promising responses are observed in cases with at least low level of CNS involvement | |
| Activity in older adults | Age has no impact on response | Limited data regarding activity but promising high response rate was observed |
| Activity in post–allo-HCT relapse setting | Response is comparable | Response is comparable |
| Impact of ALL genetic on activity | No impact of genetics on response | High activity regardless of genetics |
| High response in Ph-like ALL66 | One study correlated TP53 mutation with lower response27 | |
| The impact of high disease burden | High disease burden is associated with lower activity and higher toxicity | The impact of disease burden on response is mixed, however, OS and EFS appears lower in 1 study |
| High disease burden is associated with higher toxicity | ||
| CD19− relapse after initial response* | Of reported studies, 15 of 53 relapses (28%) following blinatumomab were CD19− | Of the reported studies, 33 of 83 relapses (40%) following CD19CAR were CD19− |
| Induction of GVHD in post–allo-HCT setting | Uncommon (11%), and the majority were low grade | Rare (none to only few cases with low grade in reported studies) |
| Severe CRS | Less common (0% to 6%) | It is more common (23% to 47%) |
| Severe neurotoxicity (≥3) | Less common (9% to 13%), more frequently in elderly (28% vs 13%), reversible and usually short-lived | More common (13% to 50%), usually reversible but lasts for longer duration (median ∼10 d) |
| Sequence of therapy | Limited data on the activity of blinatumomab after CD19CAR | No impact of prior history of blinatumomab on CD19CAR T activity, as long as CD19 expression is retained |
| Consolidation with allo-HCT | Data support consolidation with allo-HCT in r/r ALL | Durable remission is observed following CD19CAR (U Penn and MSKCC) but not with the NCI or the Chinese CD19CAR |
| Preliminary data are encouraging in blinatumomab administered for MRD+ ALL in which durable remission without allo-HCT was observed |
CR1, first complete remission; Ph, Philadelphia chromosome. See Tables 1 and 2 for expansion of other abbreviations.
Numbers were calculated by summing all reported cases of relapses and CD19− loss at relapse in Tables 1 and 2 following CD19-targeted immunotherapy.