Blood cancers

Ibrutinib and venetoclax: an all oral, all novel, chemo-free combo for CLL

Professor Constantine Tam

Professor Constantine Tam

The combination of ibrutinib and venetoclax is a viable treatment option for patients with CLL, according to new research presented at ASH 2019.

Professor Constantine Tam, from the Peter MacCallum Cancer Centre in Melbourne, presented the findings of the international multicentre CAPTIVATE study.

He told delegates that the combination of ibrutinib and venetoclax had previously been shown to be synergistic in preclinical models and tolerable in single centre studies.

“Ibrutinib is the only once-daily oral BTK inhibitor shown to increase OS and PFS in multiple phase 3 studies and ongoing ibrutinib is standard of care for patients with CLL. With the advent of the other agents, there is now increasing interest to develop time-limited therapy – one of which includes venetoclax,” he said.

The 164 enrolled patients, with previously untreated CLL and a relatively young median age of 58 years, first received three months treatment with ibrutinib in order to debulk the disease and reduce the risk of tumour lysis syndrome (TLS).

Almost a quarter (24%) of patients were judged to be at high tumour lysis risk at baseline but this reduced by 90% to only 2% after the lead-in with ibrutinib monotherapy.

Patients then received 12 cycles of ibrutinib and venetoclax in combination for a total of 15 months of therapy.

Overall 90% of the enrolled cohort completed therapy indicating the treatment was well tolerated.

Adverse events with the combination included diarrhoea, nausea, vomiting and neutropenia but only 5% of the total cohort had to discontinue the drugs because of an adverse event.

TLS was reported in three patients but on further investigation only one case met the criteria for true TLS.

Professor Tam said high rates of MRD negativity were observed – 75% in peripheral blood and 72% in bone marrow – irrespective of adverse clinical characteristics including those with p53 abnormalities, IGHV status and complex karyotype.

He said the results of the study validate the synergism seen between the two drugs in preclinical studies.

“This is an important combination because it is all oral, all novel, chemotherapy free treatment,” he told the limbic.

“At the moment, probably the most needy groups are younger patients because for some of them, time-limited therapy is really important. You need good regimens to get them into MRD negativity.”

“This regimen has the highest rate of MRD negativity. It is going to be expensive but it’s 12 months of treatment then patients are MRD negative and can get off treatment.”

He said the other group of patients it may be best suited for were those with IGHV mutations.

“In order to achieve cure with novel agents, you need to get them into deep MRD negativity so once again, of all the novel regimens out there, this is the one regimen with the best chance of replicating the cure rate in the IGHV mutated patients.”

“There is additional GI toxicity such as diarrhoea and nausea but apart from that, the risks are fairly low.”

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