We have a distance to go to achieve a cure, but it is a shorter distance with these new drugs.
—Kanti Rai, MD
In a separate interview, Kanti Rai, MD, of the Northwell Health System in New Hyde Park, New York, noted that venetoclax is one of several “exciting recent developments in this disease.” There is the Bruton tyrosine kinase inhibitor ibrutinib (Imbruvica), the PI3K inhibitor idelalisib (Zydelig), the anti-CD20 obinutuzumab (Gazyva), “which has been shown to be more powerful than rituximab [Rituxan],” and now the Bcl-2 inhibitor venetoclax.
“Venetoclax comes at the right time, when the treatment of CLL is becoming more targeted. Ibrutinib and idelalisib differ from classic chemotherapy, which indiscriminately kills normal and malignant cells. One of the key abnormalities in CLL is that CLL cells are protected from programmed cell death by the excessive presence of the inhibitor protein Bcl-2. If we can successfully inhibit Bcl-2, then the leukemic cell has no protective survival advantage,” Dr Rai continued.
“Venetoclax, perhaps, offers a unique opportunity to maximize the therapeutic potential of ibrutinib and idelalisib,” he added. “The potential of adding venetoclax opens the whole field of combining this drug with other therapies to improve outcomes of this disease. Two small studies of combination therapy bear this out.”
A Potential Drawback
“My reservation about venetoclax is that it is so effective in killing leukemic cells that it can cause tumor lysis syndrome. Experience with tumor lysis syndrome sobered up the company and investigators to come up with a new dosing schedule. Patients at high risk of tumor lysis syndrome need to be admitted to the hospital, with frequent blood tests two to three times a day. This is a potential drawback that puts pressure on the patient, the public, the health-care system, and insurers. Physicians who will be using this new and effective drug should be cautioned about the need for hospitalization of patients, even if this is an orally administered agent and even if the need for hospitalization is only for 1 to 2 days,” noted Dr. Rai.
Progress but Not a Cure
“People often exaggerate the benefits of new drugs. I am grateful for these new drugs that represent significant progress, but we need to recognize that they do not represent a cure. We have a distance to go to achieve a cure, but that distance has been rendered shorter because of these new drugs. We can measure our progress in inches, but we still need to go several additional feet or yards. Combining a venetoclax type of drug with an idelalisib type of drug or an ibrutinib type of drug might bring us closer to a cure by yards,” Dr. Rai concluded. ■
Disclosure: Dr. Rai reported no potential conflicts of interest.
Venetoclax, the latest entry into the field of treatment of chronic lymphocytic leukemia (CLL), is a powerful investigational therapy that promises to fill an important niche: treatment of high-risk relapsed/refractory patients with deletions of 17p. Nearly 80% of patients with relapsed/refractory...