One-third of patients with previously treated chronic lymphocytic leukaemia (CLL) had no detectable disease after six months of combination therapy with the targeted agents ibrutinib and venetoclax, with no increase in the occurrence of tumour lysis syndrome (TLS), a serious treatment side effect, researchers reported.

This data was presented in a press conference at the 2017 ASH annual meeting. 

For more information watch our interview with Prof Hillmen.

Of 36 patients who completed six months of combination treatment, all responded and 33 percent achieved the deepest measurable level of remission, with no detectable disease in the bone marrow, said lead study author Peter Hillmen, MBChB, PhD, professor of experimental haematology at Leeds Institute of Cancer and Pathology in the UK.

“These initial results are particularly impressive in a patient population for whom previous therapies have failed,” he said.

“We have shown that the two drugs can be given in combination without obvious additional toxicity, and the inability to detect disease with the most sensitive tools we have is a very good sign that the combination is proving to be an effective treatment.”

Ibrutinib works by blocking signals that stimulate cancerous cells to multiply, whereas venetoclax promotes tumour cell death by blocking a protein that helps the cells survive.

Both medications are approved by the FDA as single-agent therapies to treat CLL.

Because the mechanisms of action of the two drugs are complementary, Dr. Hillmen and his colleagues wanted to evaluate them as combination therapy.

The Phase III CLARITY trial enrolled a total of 50 patients with CLL that had relapsed or had not responded to prior treatment.

Patients’ median age was 64 years.

After eight weeks of treatment with ibrutinib alone, venetoclax was added at a low dose that increased over several weeks.

Before starting venetoclax, patients also began taking a drug to prevent tumour lysis syndrome (TLS), organ damage caused by a buildup in the bloodstream of uric acid and other waste products of cancer cell death.

To date, only one patient in the CLARITY trial has developed TLS and was safely treated without adverse effects.

“We have not seen an increase in the rate of TLS with the combination regimen compared with what we would expect to see with venetoclax single-agent therapy,” Dr. Hillmen said.

After six months of combination therapy, the trial has already exceeded the expected proportion of patients achieving undetectable CLL, Dr. Hillmen added.

“Our assumption was that the trial would be a success if 30 percent of patients achieved the deepest level of remission after 12 months of combination therapy,” he said.

“But already, at six months, 33 percent of patients have undetectable disease.”

Results for the trial’s secondary endpoints of safety and absence of detectable disease in the bone marrow after six and 24 months of combination therapy will be reported at a later time, Dr. Hillmen said.

A key limitation of the study is that it lacked a control group.

On the basis of the CLARITY results, Dr. Hillmen is leading a randomized controlled Phase III trial, the FLAIR trial, to compare the ibrutinib plus venetoclax combination with both ibrutinib alone and a combined regimen of three chemotherapy drugs in patients with previously untreated CLL.

Source: ASH 2017