Fixed-Length Ibrutinib-Venetoclax Promising in First-Line CLL

A mounted-duration, first-line combination of ibrutinib (Imbruvica) plus venetoclax (Venclexta) looked doubtless for chronic lymphocytic leukemia (CLL) patients who accomplished undetectable minimal residual disease (MRD) space, outcomes of the randomized CAPTIVATE see confirmed.

With a median follow-up of 16.6 months, the 1-year disease-free survival (DFS) price became as soon as now not tremendously varied between the team who persevered on ibrutinib monotherapy following combination remedy, and these assigned to placebo (100% vs 95.3%; P=0.1475), reported William Wierda, MD, PhD, of MD Anderson Cancer Heart in Houston.

The findings make stronger “a mounted-duration remedy with 12 cycles of mixed ibrutinib plus venetoclax, and remedy discontinuation for patients who raze confirmed undetectable MRD,” Wierda mentioned throughout his presentation at the American Society of Hematology (ASH) digital assembly.

However he stopped attempting calling the outcomes of the allotment II trial observe-altering, pronouncing further info are wanted from ongoing allotment III trials.

“Right here is an preliminary see, it be a multicenter, global see, and it clearly reveals the efficacy by technique of depth of remission with this combination,” mentioned Wierda.

The MRD cohort of the allotment II CAPTIVATE see integrated 164 CLL/minute lymphocytic lymphoma patients who obtained first-line remedy with ibrutinib plus venetoclax (three cycles of daily 420 mg ibrutinib by myself, then 12 cycles of ibrutinib and venetoclax, as much as 400 mg). Previously reported outcomes confirmed that the principle-line combination ended in undetectable MRD in three-fourths of patients (75% in peripheral blood; 72% in bone marrow).

Patients with confirmed undetectable MRD (n=86) at the raze of the mix interval had been then randomized 1:1 to both further remedy with ibrutinib by myself or to placebo, whereas patients with unconfirmed undetectable MRD (n=63) had been randomized 1:1 to ibrutinib by myself or persevered combination remedy. (Fifteen patients weren’t eligible for randomization).

All the plot thru all randomized palms, the 30-months development-free survival (PFS) price from the time of preliminary remedy became as soon as increased than 95%. In the confirmed undetectable MRD team, the 30-months PFS became as soon as 95.3% with placebo and 100% with ibrutinib. In the unconfirmed undetectable team, rates had been 95.2% with ibrutinib monotherapy and 96.7% with combination remedy.

For patients who did now not raze confirmed undetectable MRD at the raze of 12 cycles of combination remedy, increased enhancements in MRD space became as soon as viewed with persevered mixed remedy versus single-agent ibrutinib.

In bone marrow, the fitting total undetectable MRD rates improved from 32% after preliminary combination remedy to 42% with ibrutinib monotherapy, whereas bettering from 31% to 66% among these assigned to persevered ibrutinib plus venetoclax. In peripheral blood, the price remained regular at 45% with the switch to ibrutinib monotherapy and improved from 50% to 69% with persevered combination remedy.

“We have not got a adequate quantity of info but to be prescriptive about duration of remedy with these combinations,” Wierda mentioned throughout a quiz and resolution piece. He much that in stories of the mix performed at MD Anderson, some patients hold remained MRD definite even after 24 cycles of combination remedy.

He much that there hold been no security concerns with the “extremely energetic combination.”

Few patients required dose adjustment or drug discontinuation. Detrimental events (AEs) came about most most continuously throughout the preliminary combination interval sooner than randomization, and tended to decrease thereafter, mentioned Wierda. The most overall grade 3/4 AEs integrated neutropenia in 36%, hypertension in 10%, and thrombocytopenia and diarrhea in 5% every.

See Particulars

Patients had a median age of 58, 60% had unmutated IGHV, 20% had del(17p) or TP53 mutations, 19% had advanced karyotype, and 17% had del(11q). Extra than a third of patients had one or extra cytopenias, 32% had beefy lymph nodes (?5 cm), and three-fourths had an absolute lymphocyte depend of increased than 25 × 10⁹/L at enrollment.

Wierda pointed out that the lead-in allotment of ibrutinib shifted 90% of patients at excessive risk for tumor lysis syndrome — a identified complication with venetoclax — to medium or low risk. Total, 82% started the mix piece with out hospitalization.

Undetectable MRD (<10^-4 by 8-coloration float cytometry) became as soon as confirmed serially over three cycles in each and every the peripheral blood and bone marrow. The DFS price became as soon as defined because the proportion of patients who remained MRD detrimental and with out scientific development or death.

A much bigger share of patients with unmutated IGHV disease ended up having confirmed undetectable MRD (70% vs 46% in the unconfirmed arm). For randomization imbalances, Wierda much a style toward a much bigger share of patients with excessive-risk components assigned to ibrutinib in the confirmed undetectable MRD team.