Comparison of phase 3 studies for blinatumomab vs chemotherapy and inotuzumab vs chemotherapy
| . | Blinatumomab44 . | Inotuzumab50 . |
|---|---|---|
| Study design | Randomized phase 3, open label, 2:1 | Randomized phase 3, open label, 1:1 |
| Prestratification for previous salvage therapy (yes vs no), age <35 vs >35, previous allogeneic HSCT (yes vs no) | Pre-stratification for duration of first remission <12 mo vs >12 mo, number of salvage treatments (1st vs 2nd) and age <55 y vs >55 y) | |
| Patient population | Primary refractory, relapse <12 mo after initial treatment, second or greater relapse, relapse after allogeneic HSCT (17%) | Patients after 1-2 salvage treatments or with primary induction failure. Relapse after allogeneic HSCT included. |
| Investigational treatment (and schedule) | Continuous daily infusion: blinatumomab 9 μg/d during wk 1 of induction, then 28 μg/day; administered via continuous infusion for 28 d with 14 d off in between, cycles 42 d | Weekly infusion: inotuzumab weekly; 0.8 mg IV on d 1, 0.5 mg IV d 8, 15; induction = 21-d cycle, subsequent cycles 28 d |
| Comparator treatments | FLAG (fludarabine, cytarabine, GCSF) | FLAG (fludarabine, cytarabine, GCSF) |
| High dose cytarabine | Cytarabine + mitoxantrone | |
| High dose methotrexate-based regimen | High dose cytarabine | |
| Clofarabine-based regimen | ||
| Number of patients | 405 (all included in analysis) | 326 (281 in ITT analysis) |
| Inclusion of Ph+ patients | No | Yes |
| Response rate (CR + CRh + CRi) vs control | 44% (vs 25% in the control) P = .001 | 80.7% (vs 29.4% in control) P < .004 |
| % MRD negative (of the responders) | 76% (vs 48% in the control) P value not reported | 78.4% vs 28.1%, P < .001 |
| Responses in subgroups (vs control) | 1st salvage 52.6% (vs 35.4%) | 1st salvage 87.7% (vs 28.8%) |
| 2nd salvage 39.6% (vs 16.3%) | 2nd salvage 66.7% (vs 30.6%) | |
| 3rd or more 34.8% (vs 11.5%) | Previous allogeneic HSCT 76.5% (vs 27.3%) | |
| Previous allogeneic HSCT 40.4% (10.9%) | No prior transplant 81.5% (vs 29.9%) | |
| No prior transplant 45.8% (vs 31.8%) | BM blasts <50%-86.7% (vs 41.4%) | |
| BM blasts <50% 65.5% (vs 34.2%) | BM blasts >50%-77.9% (vs 24.4%) | |
| BM blasts >50% 34.4% (vs 24.6%) | Age <55 y 80.3% (vs 31.9%) | |
| Age <35 43.1% (vs 25.0%) | Age >55 y 81.4% (vs 25.0%) | |
| Age >35 44.6% (vs 24.3%) | Ph+ ALL vs normal karyotype 78.6% (vs 44.4%)* | |
| t4; 11) vs normal karyotype 33.3% (vs 33.3%)* | ||
| Survival, PFS, and OS | PFS: 7.3 mo blinatumomab vs 4.6 mo control | PFS: 5.0 mo inotuzumab vs 1.8 mo control P < .001 |
| OS: 7.7 mo blinatumomab vs 4.0 mo control P = 0.01 | OS: 7.7 mo vs 6.7 in control P = .04 | |
| Unique treatment-related toxicities | Neurologic toxicity 6% blinatumomab vs none in control group | Veno-occlusive disease 11% inotuzumab vs 1% control |
| CRS in 5% of blinatumomab vs none in control group | ||
| Subsequent transplant-related outcomes | All patients: 24% in the blinatumomab group vs 24% in the control group | All patients: 41% inotuzumab vs 11% controls P < .001 |
| OS after transplant: 74% blinatumomab vs 75% control | Duration of remission transplant 5.5 mo. INO vs 5.7 mo control |
| . | Blinatumomab44 . | Inotuzumab50 . |
|---|---|---|
| Study design | Randomized phase 3, open label, 2:1 | Randomized phase 3, open label, 1:1 |
| Prestratification for previous salvage therapy (yes vs no), age <35 vs >35, previous allogeneic HSCT (yes vs no) | Pre-stratification for duration of first remission <12 mo vs >12 mo, number of salvage treatments (1st vs 2nd) and age <55 y vs >55 y) | |
| Patient population | Primary refractory, relapse <12 mo after initial treatment, second or greater relapse, relapse after allogeneic HSCT (17%) | Patients after 1-2 salvage treatments or with primary induction failure. Relapse after allogeneic HSCT included. |
| Investigational treatment (and schedule) | Continuous daily infusion: blinatumomab 9 μg/d during wk 1 of induction, then 28 μg/day; administered via continuous infusion for 28 d with 14 d off in between, cycles 42 d | Weekly infusion: inotuzumab weekly; 0.8 mg IV on d 1, 0.5 mg IV d 8, 15; induction = 21-d cycle, subsequent cycles 28 d |
| Comparator treatments | FLAG (fludarabine, cytarabine, GCSF) | FLAG (fludarabine, cytarabine, GCSF) |
| High dose cytarabine | Cytarabine + mitoxantrone | |
| High dose methotrexate-based regimen | High dose cytarabine | |
| Clofarabine-based regimen | ||
| Number of patients | 405 (all included in analysis) | 326 (281 in ITT analysis) |
| Inclusion of Ph+ patients | No | Yes |
| Response rate (CR + CRh + CRi) vs control | 44% (vs 25% in the control) P = .001 | 80.7% (vs 29.4% in control) P < .004 |
| % MRD negative (of the responders) | 76% (vs 48% in the control) P value not reported | 78.4% vs 28.1%, P < .001 |
| Responses in subgroups (vs control) | 1st salvage 52.6% (vs 35.4%) | 1st salvage 87.7% (vs 28.8%) |
| 2nd salvage 39.6% (vs 16.3%) | 2nd salvage 66.7% (vs 30.6%) | |
| 3rd or more 34.8% (vs 11.5%) | Previous allogeneic HSCT 76.5% (vs 27.3%) | |
| Previous allogeneic HSCT 40.4% (10.9%) | No prior transplant 81.5% (vs 29.9%) | |
| No prior transplant 45.8% (vs 31.8%) | BM blasts <50%-86.7% (vs 41.4%) | |
| BM blasts <50% 65.5% (vs 34.2%) | BM blasts >50%-77.9% (vs 24.4%) | |
| BM blasts >50% 34.4% (vs 24.6%) | Age <55 y 80.3% (vs 31.9%) | |
| Age <35 43.1% (vs 25.0%) | Age >55 y 81.4% (vs 25.0%) | |
| Age >35 44.6% (vs 24.3%) | Ph+ ALL vs normal karyotype 78.6% (vs 44.4%)* | |
| t4; 11) vs normal karyotype 33.3% (vs 33.3%)* | ||
| Survival, PFS, and OS | PFS: 7.3 mo blinatumomab vs 4.6 mo control | PFS: 5.0 mo inotuzumab vs 1.8 mo control P < .001 |
| OS: 7.7 mo blinatumomab vs 4.0 mo control P = 0.01 | OS: 7.7 mo vs 6.7 in control P = .04 | |
| Unique treatment-related toxicities | Neurologic toxicity 6% blinatumomab vs none in control group | Veno-occlusive disease 11% inotuzumab vs 1% control |
| CRS in 5% of blinatumomab vs none in control group | ||
| Subsequent transplant-related outcomes | All patients: 24% in the blinatumomab group vs 24% in the control group | All patients: 41% inotuzumab vs 11% controls P < .001 |
| OS after transplant: 74% blinatumomab vs 75% control | Duration of remission transplant 5.5 mo. INO vs 5.7 mo control |
CRS, cytokine release syndrome; HSCT, hematopoietic stem cell transplant; ITT, intention to treat; PFS, progression-free survival.
No significant difference between inotuzumab and control group.