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

Result:

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).

Conclusion:

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.

Commentary:

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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