UNITY-CLL: Umbralisib + ublituximab prolongs PFS in CLL

A combination therapy of umbralisib + ublituximab (U2) significantly improves progression-free survival (PFS) in patients with chronic lymphocytic leukaemia (CLL) compared with obinutuzumab + chlorambucil (O+Chl), according to the UNITY-CLL* study presented at ASH 2020.

This multicentre, phase III trial involved 421 patients (median age 67 years, 66 percent male) who were treatment-naïve (n=240) and had relapsed/refractory (R/R) CLL (n=181). Participants were randomized to receive either U2** (n=210) or O+Chl*** (n=211) for 28 days in each cycle. [ASH 2020, abstract 543]

As assessed by an independent review committee, patients who received U2 had a significantly longer PFS than those who received O+Chl at a median follow-up of 36.2 months (median 31.9 vs 17.9 months; hazard ratio [HR], 0.546; p<0.0001).

The estimated 24-month PFS rate was also higher in the U2 arm vs the O+Chl arm (60.8 percent vs 40.4 percent).

The PFS benefit with U2 was consistent among all subgroups of treatment-naïve (median 38.5 vs 26.1 months; HR, 0.482) and R/R patients (median 19.5 vs 12.9 months; HR, 0.601) compared with O+Chl.

Patients on U2 also demonstrated a longer treatment duration than those on O+Chl (median 23 vs 5 months), with a significantly higher overall response rate (ORR; 83.3 percent vs 68.7 percent, respectively; p<0.001).

Among the 26 patients who were previously treated with ibrutinib, a higher ORR was also observed in the U2 arm vs the O+Chl arm (57.0 percent vs 25.0 percent).

Neutropenia (30.6 percent vs 34.7 percent), thrombocytopenia (3.4 percent vs 13.1 percent), and diarrhoea (12.1 percent vs 2.5 percent) were the most common grade 3–4 adverse events reported in the U2 vs the O+Chl arms, with 34 and 16 patients, respectively, discontinuing treatment.

“[This] is the first randomized phase III study in CLL of a PI3Ki … in treatment-naive CLL. U2 exhibited a well-tolerated safety profile, and significantly improved PFS vs standard of care chemoimmunotherapy in patients with treatment-naive and R/R CLL,” the researchers concluded.

*UNITY-CLL: Ublituximab + TGR-1202 compared to obinutuzumab + chlorambucil in patients with untreated and previously treated chronic lymphocytic leukemia

**U2 dosage: Umbralisib 800 mg once/day orally; and ublituximab 900 mg IV on days 1/2 (split 150/750 mg), 8, and 15 of cycle 1; day 1 of cycles 2–6; and day 1 of every 3 cycles after cycle 6

***O+Chl dosage: Obinutuzumab 1,000 mg IV on days 1/2 [split 100/900], 8, and 15 of cycle 1; day 1 of cycles 2–6; and chlorambucil 0.5 mg/kg orally on days 1 and 15 of cycles 1–6