Frontline CLL studies with BTKi ± anti-CD20 monoclonal antibody
| Study . | Targeted regimen . | Comparator . | N (targeted regimen) . | ORR, % . | CRR, % . | uMRD, % . | PFS . | OS . | Notable AEs . | Median follow-up, mo . |
|---|---|---|---|---|---|---|---|---|---|---|
| E191215 | IR | FCR | IR = 354 | 95 | 17 | 8 (*n = 276) | NR (3-y 89%) | NR (3-y 98%) | Grade ≥3 infections: FCR = 20.3% vs IR = 10.5%; grade ≥3 HTN: FCR = 8.2% vs IR = 18.8% | 33.6 |
| A04120216 | I ± R | BR | I = 182 IR = 182 | I = 93 IR = 94 | I = 7 IR = 12 | I = 1 IR = 4 | I = NR (2-y 87%) IR = NR (2-y 88%) | I = NR (2-y 90%) IR = NR (2-y 94%) | Grade ≥3 neutropenia: IR = 21% vs I = 15% | 38 |
| NCT0200704417 | IR | Ibrutinib | I = 104 IR = 104 TN = 27 RR = 181 | I = 92.3 IR = 92.3 | I = 20.2 IR = 26 | NA | I = NR (3-y 86%) IR = NR (3-y 86.9%) | I = NR (3-y 89%) IR = NR (3-y 92%) | No significant difference in toxicity profile | 36 |
| iLLUMINATE18 | IO | Chl-O | IO = 113 | 88 | 19 | 35 (*n = 113) | NR (30-mo 79%) | NR (30-mo 86%) | SAEs in 58% of IO and 35% of Chl-O; obinutuzumab-related SAEs (febrile neutropenia, thrombocytopenia) in 15% of the IO arm | 31.3 |
| ELEVATE TN19 | A ± O | Chl-O | A = 179 AO = 179 | A = 86 AO = 94 | A = 1 AO = 13 | A = 7% of those in CR/CRi (*n = 14) AO = 56% of those in CR/CRi (*n = 43) | A = NR (2-y 87%) AO = NR (2-y 93%) | A = NR (2-y 95%) AO = NR (2-y 95%) | Grade ≥3 neutropenia: AO = 30% vs A = 10%; grade ≥3 infections: AO = 21% vs A = 14% | 28.3 |
| Study . | Targeted regimen . | Comparator . | N (targeted regimen) . | ORR, % . | CRR, % . | uMRD, % . | PFS . | OS . | Notable AEs . | Median follow-up, mo . |
|---|---|---|---|---|---|---|---|---|---|---|
| E191215 | IR | FCR | IR = 354 | 95 | 17 | 8 (*n = 276) | NR (3-y 89%) | NR (3-y 98%) | Grade ≥3 infections: FCR = 20.3% vs IR = 10.5%; grade ≥3 HTN: FCR = 8.2% vs IR = 18.8% | 33.6 |
| A04120216 | I ± R | BR | I = 182 IR = 182 | I = 93 IR = 94 | I = 7 IR = 12 | I = 1 IR = 4 | I = NR (2-y 87%) IR = NR (2-y 88%) | I = NR (2-y 90%) IR = NR (2-y 94%) | Grade ≥3 neutropenia: IR = 21% vs I = 15% | 38 |
| NCT0200704417 | IR | Ibrutinib | I = 104 IR = 104 TN = 27 RR = 181 | I = 92.3 IR = 92.3 | I = 20.2 IR = 26 | NA | I = NR (3-y 86%) IR = NR (3-y 86.9%) | I = NR (3-y 89%) IR = NR (3-y 92%) | No significant difference in toxicity profile | 36 |
| iLLUMINATE18 | IO | Chl-O | IO = 113 | 88 | 19 | 35 (*n = 113) | NR (30-mo 79%) | NR (30-mo 86%) | SAEs in 58% of IO and 35% of Chl-O; obinutuzumab-related SAEs (febrile neutropenia, thrombocytopenia) in 15% of the IO arm | 31.3 |
| ELEVATE TN19 | A ± O | Chl-O | A = 179 AO = 179 | A = 86 AO = 94 | A = 1 AO = 13 | A = 7% of those in CR/CRi (*n = 14) AO = 56% of those in CR/CRi (*n = 43) | A = NR (2-y 87%) AO = NR (2-y 93%) | A = NR (2-y 95%) AO = NR (2-y 95%) | Grade ≥3 neutropenia: AO = 30% vs A = 10%; grade ≥3 infections: AO = 21% vs A = 14% | 28.3 |
*Of those evaluable for uMRD in the bone marrow/peripheral blood.
A, acalabrutinib; AE, adverse event; CRi, complete response with incomplete count recovery; CRR, complete response rate; HTN, hypertension; I, ibrutinib; IO, ibrutinib and obinutuzumab; NA, not available; NR, not reached; RR, relapsed/refractory; SAE, serious adverse event; TN, treatment-naive.