Ibrutinib, idelalisib, venetoclax provide ‘very exciting developments’ in CLL

Recent discoveries involving ibrutinib, idelalisib and venetoclax have had a tremendous impact on life expectancy and quality of life in patients with chronic lymphocytic leukemia, according to Kanti R. Rai, MD, chief of the CLL research and treatment program at North Shore-LIJ Cancer Institute and a HemOnc Today Editorial Board member.

There have been “very exciting” developments over the last decade in the treatment of CLL, he told HemOnc Today.

Kanti R. Rai

Kanti R. Rai

Ibrutinib (Imbruvica, Pharmacyclics) was initially approved by the FDA for patients with relapsed and refractory CLL for whom previous treatments were no longer effective.

“This is a drug which gave a tremendous boost to the morale and hopes of previously treated relapsed, refractory CLL patients,” Rai said.

More recently, the results of a phase 3 randomized trial led the FDA to expand the approval of ibrutinib to include first-line treatment of patients with CLL, he said.

“Ibrutinib is a new drug which has been approved for not only relapsed and refractory CLL patients, but also for front-line CLL patients who need treatment,” he said. “In addition, ibrutinib has also been approved for one of the worst prognostic groups of CLL – 17p deletion.”

Combination therapy with idelalisib (Zydelig, Gilead) and rituximab (Rituxan; Genentech, Biogen Idec) has resulted in extraordinary response rates in previously treated patients with relapsed and refractory CLL, Rai said. Clinicians should be aware that the combination therapy does increase the risk of some adverse events.

“Most of the toxicities are tolerable grade 1 or grade 2, and infrequently severe toxicities occur – which include diarrhea which starts to happen most often after 8 to 10 months of use of idelalisib,” he said.

In addition, venetoclax (Venclexta; Genentech, AbbVie), a small molecular inhibitor of the BCL-2 protein, recently received FDA approval for the treatment of 17p deletion in CLL.

Although there have been recent FDA approvals of various treatments that have expanded the use of venetoclax, idelalisib and ibrutinib, Rai said there are more trials that could expand treatment options even further.

“I must conclude with this that there are other drugs in the same BCR inhibition category, newer drugs in BTK inhibition – which is a new drug which in initial trials seems to be less toxic and more effective than ibrutinib – but those trials are currently ongoing and we will know in about 2 years whether [acalabrutinib] is superior to ibrutinib,” he said. “We have everything good to hope for in the coming couple of years.”  – by Ryan McDonald

Disclosure: Rai reports medical advisory board roles with Celgene, Genentech/Roche, Gilead and Pharmacyclics.

Editor's Note: This story was updated on Aug. 4 to clarify the use of acalabrutinib in a trial.

Recent discoveries involving ibrutinib, idelalisib and venetoclax have had a tremendous impact on life expectancy and quality of life in patients with chronic lymphocytic leukemia, according to Kanti R. Rai, MD, chief of the CLL research and treatment program at North Shore-LIJ Cancer Institute and a HemOnc Today Editorial Board member.

There have been “very exciting” developments over the last decade in the treatment of CLL, he told HemOnc Today.

Kanti R. Rai

Kanti R. Rai

Ibrutinib (Imbruvica, Pharmacyclics) was initially approved by the FDA for patients with relapsed and refractory CLL for whom previous treatments were no longer effective.

“This is a drug which gave a tremendous boost to the morale and hopes of previously treated relapsed, refractory CLL patients,” Rai said.

More recently, the results of a phase 3 randomized trial led the FDA to expand the approval of ibrutinib to include first-line treatment of patients with CLL, he said.

“Ibrutinib is a new drug which has been approved for not only relapsed and refractory CLL patients, but also for front-line CLL patients who need treatment,” he said. “In addition, ibrutinib has also been approved for one of the worst prognostic groups of CLL – 17p deletion.”

Combination therapy with idelalisib (Zydelig, Gilead) and rituximab (Rituxan; Genentech, Biogen Idec) has resulted in extraordinary response rates in previously treated patients with relapsed and refractory CLL, Rai said. Clinicians should be aware that the combination therapy does increase the risk of some adverse events.

“Most of the toxicities are tolerable grade 1 or grade 2, and infrequently severe toxicities occur – which include diarrhea which starts to happen most often after 8 to 10 months of use of idelalisib,” he said.

In addition, venetoclax (Venclexta; Genentech, AbbVie), a small molecular inhibitor of the BCL-2 protein, recently received FDA approval for the treatment of 17p deletion in CLL.

Although there have been recent FDA approvals of various treatments that have expanded the use of venetoclax, idelalisib and ibrutinib, Rai said there are more trials that could expand treatment options even further.

“I must conclude with this that there are other drugs in the same BCR inhibition category, newer drugs in BTK inhibition – which is a new drug which in initial trials seems to be less toxic and more effective than ibrutinib – but those trials are currently ongoing and we will know in about 2 years whether [acalabrutinib] is superior to ibrutinib,” he said. “We have everything good to hope for in the coming couple of years.”  – by Ryan McDonald

Disclosure: Rai reports medical advisory board roles with Celgene, Genentech/Roche, Gilead and Pharmacyclics.

Editor's Note: This story was updated on Aug. 4 to clarify the use of acalabrutinib in a trial.

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