Initial results of MRD driven time limited therapy with zanubrutinib, obinutuzumab, and venetoclax

Initial results of a multicenter, investigator initiated study of MRD driven time limited therapy with zanubrutinib, obinutuzumab, and venetoclax

Abstract Number: 8006

Abstract Type : Oral Abstract Session

Indication : Chronic Lymphocytic Leukemia

Intervention : Zanubrutinib, Obinutuzumab, and Venetoclax

Company : BeiGene

Technology : Small molecule


The study accrued 39 pts (3-10/19): med age 59 years (23-73), 3:1 male, CLL IPI >4 26/39 (67%), unmutated IGHV 28/39 (72%), 17p del/TP53 mutated 4/39 (10%), all pts were evaluable for toxicity with 37 evaluable for efficacy. At a med follow up of 8 months (mo; 3-10), 25/37 (68%) pts achieved PB uMRD. Med time to PB uMRD is 6 mo (4-8+). Another 8/37 (22%) had PB MRD < 0.1%. Of 25 with PB uMRD, 19 had BM uMRD with 10/19 completing 2 additional cycles and discontinued; 3 had BM MRD (all <0.02%); 3 pending. The most common tx emergent AEs were neutropenia (49%), infusion related reaction (41%), bruising (39%), and diarrhea (39%). Grade ≥3 AEs in ≥5% pts were neutropenia (13%), thrombocytopenia (5%), rash (5%), and pneumonia (5%). Of 17 pts at high risk for TLS on C1D1, 2 cycles of BO reduced TLS risk to low/medium at Ven initiation in 15 (88%). No pts had laboratory/clinical TLS (Howard).


BOVen is well tolerated and achieves rapid uMRD: currently 68% PB uMRD and 51% BM uMRD with limited follow up (to be updated on presentation). Ten (27%) have discontinued treatment thus far. The value of MRD directed treatment duration will be evaluated with continued follow up.


Combination regimen of Zanubritinib, Obinituzumab and Venetoclax has achieved impressive overall uMRD of 77.1% at 8 mos follow up, warrants further investigation of MRD related treatment duration

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