Table 2.

Reported frontline studies with triplet regimens in CLL

AgentsStudyRegimenPatient populationPFSuMRD rateMedian follow-up
Ibrutinib-venetoclax-obinutuzumab Phase 2 IVO Median age: 58 Median: 88.5 months Marrow: 56%a 85.6 months (first 25 TN patients) 
CLL2-GIVe IVO Median age: 62
All patients had altered TP53 
Estimated 3-year: 79.9% Blood: 78%b NR 
GAIA/CLL1319  IVO Mean age: 60.7
Median CIRS score: 2 
Estimated 4-year: 85.5% Blood: 92.2%c 50.7 months 
A04170228  IVO Median age: 74 Estimated 18-month: 85% Marrow: 86.7%d 14 months 
Acalabrutinib-venetoclax-obinutuzumab Phase 229  AVO Median age: 63 At 27.6 months: 100% Blood: 86%e
Marrow: 86% 
27.6 months 
Zanubrutinib-venetoclax-obinutuzumab BOVen30  ZVO Median age: 62 One progression event, 2 deaths Both blood and marrow: 89%f 25.8 months 
AgentsStudyRegimenPatient populationPFSuMRD rateMedian follow-up
Ibrutinib-venetoclax-obinutuzumab Phase 2 IVO Median age: 58 Median: 88.5 months Marrow: 56%a 85.6 months (first 25 TN patients) 
CLL2-GIVe IVO Median age: 62
All patients had altered TP53 
Estimated 3-year: 79.9% Blood: 78%b NR 
GAIA/CLL1319  IVO Mean age: 60.7
Median CIRS score: 2 
Estimated 4-year: 85.5% Blood: 92.2%c 50.7 months 
A04170228  IVO Median age: 74 Estimated 18-month: 85% Marrow: 86.7%d 14 months 
Acalabrutinib-venetoclax-obinutuzumab Phase 229  AVO Median age: 63 At 27.6 months: 100% Blood: 86%e
Marrow: 86% 
27.6 months 
Zanubrutinib-venetoclax-obinutuzumab BOVen30  ZVO Median age: 62 One progression event, 2 deaths Both blood and marrow: 89%f 25.8 months 

aAt end of therapy; bAt cycle 12; cAt month 15; dAt cycle 15; eAt start of cycle 16; fBest uMRD at follow-up.

Regimens: AVO, acalabrutinib, venetoclax, and obinutuzumab; IVO, ibrutinib, venetoclax, and obinutuzumab; ZVO, zanubrutinib, venetoclax, and obinutuzumab. NR, not reported; PFS, progression-free survival; uMRD, undetectable measurable residual disease.

Estimated 4-year: 85.5%.

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