AbbVie, a global biopharmaceutical company, announced updated results of a phase 1b study that showed patients with relapsed/refractory chronic lymphocytic leukaemia (CLL) taking venetoclax, an investigational B-cell lymphoma 2 (BCL-2) selective inhibitor, in combination with rituximab, had an overall response rate (ORR) of 84 per cent (n=41/49).
Additionally, six patients stopped venetoclax after achieving either a complete response (CR) or CR with incomplete marrow recovery (CRi). Three patients maintained a response after a median of 12 months (0-21). These data were detailed in an oral presentation at the 20th Congress of the European Hematology Association (EHA), June 11-15, in Vienna.
"Potentially, the most interesting part of these initial results is the data regarding the patients who have been able to come off treatment and who continue to maintain their complete response," said professor Andrew W. Roberts, MBBS, FRACP, FRCPA, PhD, the Royal Melbourne Hospital Department of Clinical Haematology and Bone Marrow Transplant Service, Australia, and head of clinical translation at the Walter and Eliza Hall Institute of Medical Research. "The fact that this investigational venetoclax combination achieved these response rates suggests this treatment may offer patients another option and warrants further investigation."
CLL is the most common leukaemia diagnosed in adults in western countries. In the United States, CLL accounts for approximately 14,620 new cases of leukaemia diagnosed each year. It is a slow-progressing cancer of the blood and bone marrow in which the bone marrow makes too many lymphocytes, a type of white blood cell that helps the body fight infection. The cause of CLL is unknown, though researchers believe it may be linked to a genetic mutation.
"AbbVie's goal is to develop treatments that can help patients with hard-to-treat cancers," said Gary Gordon, M.D., vice president, oncology development, AbbVie.
"Combining the potential of venetoclax with rituximab is just one example of how we are investigating combination therapy."
The phase 1b, open-label, dose-escalation, multicenter, international study assessed the maximum tolerated dose and safety of venetoclax combined with rituximab in patients with relapsed/refractory CLL or small lymphocytic leukaemia (SLL); secondary objectives included pharmacokinetics and preliminary efficacy.
Of the 49 patients evaluated, the overall response rate (ORR) was 84 per cent (n=41/49), with 20 (41 per cent) patients achieving a complete response (six patients achieved complete response with incomplete bone marrow recovery (CRi)), and 21 (43 per cent) patients achieving a partial response (PR), one nodular.
The most common overall treatment emergent adverse events (AEs) (>25 per cent patients) were neutropenia (53 per cent ), diarrhea and nausea (47 per cent), upper respiratory tract infection (41 per cent), pyrexia (37 per cent) and fatigue, headache and cough (each 33 per cent). Grade 3/4 treatment-emergent AEs (>10 per cent patients) were neutropenia (51 per cent), thrombocytopenia (16 per cent) and anemia (14 per cent). There was one treatment-emergent AE that led to death due to tumor lysis syndrome (TLS) and there were two treatment-emergent deaths after progressive disease (PD).
Venetoclax is an investigational oral B-cell lymphoma-2 (BCL-2) inhibitor being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be expressed in some cancer types. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax is being developed in collaboration with Genentech and Roche. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other cancers. In 2015, the FDA granted Breakthrough Therapy designation to venetoclax for the treatment of CLL in previously treated (relapsed/refractory) patients with the 17p deletion genetic mutation. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.