Table 4 Outcomes From Clinical Trials Evaluating Blinatumomab in Combination With Chemotherapy for Treatment of Newly Diagnosed Ph-Negative BCP-ALL.
Regimen (NCT) | Treatment Schema | Study Phase | N | Age Range | Outcome Summary |
|---|---|---|---|---|---|
Blinatumomab as a replacement for select chemotherapy cycles | |||||
ALLG ALL08: Low-intensity hyper-CVAD + blinatumomab (ACTRN12617000084381) [24] | Four cycles of low-intensity chemotherapy, alternating with 4 cycles of blinatumomab consolidation and then 2 y of POMP maintenance | 2 | 30 | 40–67 y | • Median follow-up: NR • Estimated 2-y median EFS: 61% (median EFS 36 mo) • Estimated 2-y median OS: 79% (median OS NR) • Safety: grade 3 CRS (n = 1); no treatment-related deaths |
SWOG 1318; Blinatumomab induction and prednisone + vincristine + MTX + 6-MRP (NCT02143414) [56] | Two cycles of blinatumomab induction and 3 cycles of blinatumomab consolidation followed by 18 months of POMP | 2 | 29 | 66–84 y | • MRD: 13 of 19 responders had available MRD data, with 12/13 (92%) MRD-negativity • Median follow-up: 3.14 y • Estimated 3-y DFS: 37% (95% CI: 17–57) • Estimated 3-y OS: 37% (lower 1-sided 90% CI: 26) • Binary 3-y OS: 34% (95% CI: 18–54) • Safety: most common grade 3-4 AEs, hyperglycemia (14%), dyspnea (10%), febrile neutropenia (10%), hypertension (10%), and lung infection (7%) |
Alliance A041703, blinatumomab + inotuzumab ozogamicin (NCT03739814) [57, 58] | Two cycles of inotuzumab ozogamicin induction followed by blinatumomab consolidation for 2 cycles and up to another 3 cycles | 2 | 33 | 60–84 y | • MRD: NR • Median follow-up: 22 mo • 1-y EFS: 75% (95% CI: 61–92) • 1-y OS: 84% (95% CI: 72–98) • 2 deaths in remission (n = 1 after HSCT), 1 death without remission from respiratory failure with sinusoidal occlusion syndrome of liver (n = 1) • Safety: Common grade 3-5 AEs, neutropenia (88%), thrombocytopenia (73%), anemia (42%), leukopenia (39%), lymphopenia (27%), febrile neutropenia (21%), and encephalopathy (12%) |
Mini-hyper-CVD inotuzumab ozogamicin ± blinatumomab (NCT01371630) [55] | Four (4) cycles of mini-hyper-CVAD followed by 4 cycles of blinatumomab consolidation then maintenance with alternating blocks of 3 cycles of POMP and one cycle of blinatumomab for 12 cycles. A total of 4 cycles of inotuzumab ozogamicin were given during induction | 2 | 80 | 63–72 y | • MRD: 94% negativity • Median follow-up: 92.8 mo • Median PFS (with blinatumomab): 56.4 mo (95% CI 11.3–69.7) • Median OS (with blinatumomab): 56.4 mo (95% CI 16.3–70.0) • 2-y PFS (with blinatumomab): 60.9% (95% CI: 24.0–76.5) • 5-y PFS (with blinatumomab): 41.8% (95% CI: 28.5–65.0) • 2-y OS (with blinatumomab): 59.6% (95% CI: 38.6–75.5) • 5-y OS (with blinatumomab): 40.9% (95% CI: 17.0–63.9) • Safety: most common grade 3–5 AEs, thrombocytopenia (78%), hyperglycemia (36%), febrile neutropenia (33%); no treatment-related deaths |
GMALL BOLD (NCT 03480438) [25] | One cycle dose-reduced chemotherapy + 1 cycle blinatumomab as induction, followed by 3 cycles of blinatumomab alternating with age-adapted chemotherapy as consolidation | 2 | 47 | 56–76 y | • MRD: NR • Median follow-up: 2.1 y • 3-y EFS: 60% • 1-y OS: 80% • 3-y OS: 67% • Safety: no unexpected events |
Addition of blinatumomab to chemotherapy regimens | |||||
GIMEMA LAL 1913 + sequential blinatumomab (NCT03367299) [20, 23] | Six cycles of chemotherapy with 2 cycles of sequential blinatumomab consolidation (cycles 2 and 6) | 2 | 149 | 18–65 y | • MRD: 93% negativity rate • Median follow-up: 37.5 mo • 3-y DFS: 66% • 3-y OS: 71% • Safety: not stated |
HOVON-146: Blinatumomab added to prephase and consolidation chemotherapy (based on HOVON-70)* (NCT03541083) [27, 59] | Chemotherapy with 1 cycle of prephase blinatumomab (for 2 weeks), followed by 2 cycles of blinatumomab consolidation (each 4 wk) | 2 | 71 (overall population) | 18–70 y | • MRD: 91% negativity rate (n = 56) • Median follow-up: 43 mo • 4-y EFS: 49% (Ph-negative BCP-ALL patients) • 4-y OS: 70% (Ph-negative BCP-ALL patients) • Safety: grade 3 CRS (21%) |
Chemotherapy with 5 cycles of blinatumomab consolidation and maintenance | 2 | 94 | 18–59 y | • MRD: 72% negativity rate • Median follow-up: 2.3 y • 2.5-y DFS: 72% (95% CI: 60–80) • 2.5-y OS: 79% (95% CI: 67–88) • Safety: not stated | |
Hyper-CVAD + blinatumomab (NCT02877303) [26] | Four cycles of chemotherapy, followed by 4 cycles of blinatumomab consolidation, then maintenance with alternating blocks of 3 cycles of POMP and one cycle of blinatumomab for 15 cycles | 2 | 38 | 18–39 y (n = 22) ≥40 y (n = 16) | • Median follow-up: 37 mo • 3-y RFS: 73% (95% CI: 56–85) • 3-y OS: 81% (95% CI: 65–91) vs 4-y OS hyper-CVAD • Safety: most common grade 3–5 AEs, infection or febrile neutropenia (82%); no treatment-related deaths |
Two cycles of blinatumomab, followed by 3 cycles of consolidation chemotherapy then cycle 3 of blinatumomab followed by cycle 4 of chemotherapy and then a fourth cycle of blinatumomab | 3 | 224 (blinatumo-mab plus chemo-therapy, n = 112; chemo-therapy alone, n = 112) | 30–70 y | • MRD: only MRD-negative patients included • Median follow-up: 3.6 y • 3-y OS: 85% • 3-y RFS: 80% • Safety: higher incidence of grade ≥3 neuropsychiatric AEs with blinatumomab 23% versus chemotherapy alone (5%; P < 0.001) |
