Patients with a certain kind of leukemia or lymphoma who carry a mutation that makes their cancer difficult to treat respond better to Pharmacyclics’ Imbruvica (ibrutinib) than people without the mutation, researchers discovered.
In general, patients without mutations respond to Imbruvica better, however.
The therapy’s developer, Pharmacyclics, based its conclusion about patients with the mutation on an analysis of three Phase 3 clinical trials of Imbruvica. The findings covered patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who carry the mutation.
Researchers presented the analysis of the trials’ results at the 17th International Workshop on Chronic Lymphocytic Leukemia meeting in New York, May 12-15.
“Over the past few years, we’ve seen tremendous improvements in the treatment of people with CLL and SLL,” Dr. Thomas J. Kipps, the study’s lead investigator, said in a press release. “Newly introduced medications can improve the outcome of therapy, particularly for patients with high-risk prognostic markers who typically do not respond well to standard chemotherapy.
“Analysis of the clinical data suggests an improvement in outcomes for certain high-risk CLL/SLL patients treated with Imbruvica,” added Kipps, who is also a professor at the University of California, San Diego and Moores Cancer Center.
The Phase 3 trials — RESONATE (NCT01578707), RESONATE-2 (NCT01722487) and HELIOS (NCT01611090) — compared Imbruvica with other drugs used to treat CLL and SLL.
A key focus of the research was whether Imbruvica could help people with four high-risk gene mutations. In all three trials, patients with mutations who received Imbruvica had better progression-free survival rates, overall survival rates, overall response rates, and complete response rates than patients with mutations who received comparable drugs. This was seen regardless of the mutation a patient had.
In general, patients without mutations who received Imbruvica had better outcomes than patients with mutations.
An exception was patients with a mutation known as an 11q deletion. The percentage of those with this mutation whose disease failed to progress over two years was significantly higher than the percentage of patients without the mutation — 82% versus 75%. In addition, 93 percent of those with the mutation were still alive at 30 months, compared with 86 percent of those without it, also a significant finding.
Another mutation, trisomy 12, was associated with better complete response rates to Imbruvica. Patients who had had only one round of another treatment before receiving Imbruvica were more likely to survive longer as well, researchers added.
An additional finding was that Imbruvica’s safety was the same in patients with mutations, regardless of the mutation.
Imbruvica is the first of a class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors. It was developed jointly by Janssen Biotech and AbbVie‘s Pharmacyclics unit.
Although it is approved for several types of lymphoma, including CLL and SLL, the analysis of the Phase 3 trials offered further insight into its impact on specific patient groups.
“We are encouraged by the findings from these analyses, which add to the large body of data supporting Imbruvica in treating CLL/SLL patients,” said Dr. Danelle James, head of clinical science at Pharmacyclics.
“We have one of the most robust databases for a single molecule in hematological oncology, and more than 25,000 CLL patients have been treated in the U.S. alone with Imbruvica since approval in 2014,” she said. “We continue to investigate the use of Imbruvica in high-risk patients so that ideally they too can achieve better response rates and overall outcomes to treatment.”
