Ublituximab in combination with ibrutinib demonstrated a benefit in progression-free survival over ibrutinib monotherapy, as assessed by an independent review committee, in patients with high-risk relapsed or refractory chronic lymphocytic leukemia in the final long-term results of the phase III GENUINE trial.
Ublituximab (TG-1101) in combination with ibrutinib (Imbruvica) demonstrated a benefit in progression-free survival over ibrutinib monotherapy, as assessed by an independent review committee, in patients with high-risk relapsed or refractory chronic lymphocytic leukemia (CLL) in the final long-term results of the phase III GENUINE trial.1
The complete final results after a median follow-up of more than 4 years are expected to be presented at a future medical conference and shared with the FDA for regulatory filing.
“We are pleased with the final results from the phase III GENUINE trial with median follow-up of over 4 years. The improvement in PFS observed in these [patients with] high-risk CLL is extremely encouraging, and we look forward to presenting the full data at a future medical conference,” Michael S. Weiss, executive chairman and CEO of TG Therapeutics, the company developing the glycoengineered anti-CD20 monoclonal antibody, stated in a press release.
The randomized, open-label, multicenter trial explored the combination of ublituximab plus ibrutinib as compared with ibrutinib alone in adult patients with high-risk CLL who had previously received ≥1 prior treatment regimen. High-risk CLL was defined in the trial by the presence of 17p deletion, 11q deletion, or a p53 mutation.
A total of 126 patients across 160 trial sites in the United States and Israel were randomized to either the combination regimen or ibrutinib alone. Ublituximab was administered in the investigational arm at 900 mg on days 1, 8, and 15 of cycle 1 followed by on day 1 of cycles 2 through 6. Ibrutinib was administered orally at 420 mg once daily in both arms. Those who did not progress after 6 cycles continued to receive maintenance ublituximab once every 3 months at 900 mg.
According to data previously presented at the 2017 ASCO Annual Meeting, the primary endpoint of objective response rate (ORR) by independent review committee assessment was met with an ORR of 78% in the combination arm compared with 45% in the ibrutinib monotherapy arm. The complete response in the combination arm was 7% and there were no complete responses in the ibrutinib arm. Additionally, 19% of patients in the combination arm had minimal residual disease negativity versus 2% treated with ibrutinib alone.2
When partial responses with lymphocytosis were added to the response criteria evaluations, the ORR increased to 83% with the combination regimen and 59% with single-agent ibrutinib.
The median time to response in the combination arm was 1.97 months compared with 3.8 months in the ibrutinib monotherapy arm.
The most common all-grade adverse events (AEs) reported with the combination and monotherapy, respectively, were diarrhea (42% vs 40%), fatigue (27% vs 33%), insomnia (24% vs 10%), nausea (22% vs 21%), and headache (20% vs 28%). Infusion reactions occurred in 54% of patients in the combination arm, with 5% being grade 3 or 4. Other important AEs of note included neutropenia (22% vs 12%), anemia (14% vs 17%), and thrombocytopenia (14% vs 10%).
In the long-term results, no new safety signals were observed, and the combination continued to be well tolerated.1