The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta®) to include data on minimal residual disease (MRD).
The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.
The patients were randomized to receive:
- Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m2 on day 1 for the first cycle and at 500 mg/m2 on day 1 for cycles 2 to 6 (n=194)
- Bendamustine at 70 mg/m2 on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.
“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.