The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that Health Canada has issued a Notice of Compliance (NOC) authorizing the expanded use of IMBRUVICA® (ibrutinib) in a first all-oral, fixed-duration (FD) treatment combination with venetoclax (I+V) for adults with previously untreated chronic lymphocytic leukemia (CLL), including those with 17p deletion (del 17p). This authorization is based on the pivotal Phase 3 GLOW study...

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma...SUGGESTED TREATMENT REGIMENS...CLL/SLL with del(17p)/TP53 mutation…Other recommended regimens…Ibrutinib + venetoclax…

We report long term follow-up of combined IBR and VEN in first-line CLL (n=120) with a 5-year PFS of 90.1%. The 5-year PFS for pts with del(17p)/TP53 mutation is 86.1%. Retreatment with BTK inhibitor appears effective for pts with disease relapse.

Pts aged ≤70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally)….4 y PFS rates were numerically lower in pts with uIGHV (73%) or del(17p) and/or TP53 mutation (63%), while OS rates remained consistently high (Table)....With 4 y follow-up, fixed-duration I+V continues to provide deep, durable remissions with clinically meaningful PFS and time off treatment, including in pts with high-risk disease features.

Patients were required to have at least 1 of the following features: del(17p), TP53-mutated CLL, del(11q)...Therapy consisted of ibrutinib, 420 mg/d, monotherapy for 3 cycles, thereafter combined with venetoclax....The 3-year progression-free survival was 93%, and 3-year overall survival was 96%....Remissions appeared to be durable during a follow-up of more than 3 years, with activity seen across high-risk disease subgroups, including those with del(17p)/TP53-mutated CLL.

Eligible pts were aged ≤70 y and had not received previous treatment for CLL/SLL. Pts received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally)….In the 27 pts with del(17p)/TP53 mutation, CR rate was 56%...

In pts with del(17p)/TP53 mutation (n=27), CR rate was 56%, uMRD rate was 81% (PB) and 41% (BM), and 24-mo PFS was 84% (95% CI 63–94). Of 34 pts with high baseline TLS risk based on tumor burden, 32 (94%) shifted to medium or low risk after I lead-in; no TLS occurred....First-line I+V is an all-oral, once-daily, chemotherapy-free, fixed-duration regimen that provides deep, durable responses in pts with CLL/SLL, including those with genomic high-risk features.

In pts with del(17p)/TP53 mutation (n=27), CR rate was 56%, uMRD rate was 81% (PB) and 41% (BM), and 24-mo PFS was 84% (95% CI 63–94)….First-line I+V is an all-oral, once-daily, chemotherapy-free, fixed-duration regimen that provides deep, durable responses in pts with CLL/SLL, including those with genomic high-risk features.

We designed a phase II, investigator-initiated, response-adapted clinical trial with the addition of ven to ibr in patients (pts) with one or more high risk features...High risk was defined as any of: del(17p); complex karyotype; del(11q); elevated β2-microglobulin; TP53 mutation....Ven added to ibr in pts with high-risk CLL as consolidation was well tolerated and associated with a high likelihood of achieving U-MRD in BM and CR within 12 months of combination.

The high rates of BM uMRD were consistent across high-risk subgroups, including in pts with del(17p) (75%), del(17p) or TP53 mutation (70%), del(11q) (84%), complex karyotype (83%), and unmutated IGHV status (81%)...First-line treatment with Ibr + Ven represents an all oral, once-daily, chemotherapy-free regimen that provides high rates of uMRD in both PB and BM in pts with CLL.