BTK Inhibitors Offer Improved Response Over Chemotherapy in Mantle Cell Lymphoma

Patients with relapsed/refractory mantle cell lymphoma (MCL) saw more favorable responses with the BTK inhibitor Imbruvica (ibrutinib) than with chemotherapy, according to nearly a decade of data from three clinical trials presented at the 2019 American Society of Hematology (ASH) Annual Meeting.

In an interview with CURE®’s sister publication, OncLive®, Dr. Simon Rule went into greater detail about the pooled findings of this research and the use of BTK inhibitors in MCL.

“BTK inhibitors are very exciting drugs,” said Rule, of Plymouth University Medical School in England. “When you use drugs earlier (in the treatment cycle), you get better responses, and that is what we saw, so it wasn’t a surprise. The surprise was how effective they were in the best patients. The patients who are getting the best responses to chemotherapy get even better responses with ibrutinib.”

Researchers pooled data from 370 patients over seven and a half years from the SPARK, RAY and PCYC-1104 trials, in which individuals with MCL received a dose of Imbruvica each day until the disease progressed or they experienced unacceptable toxicity. The patients who benefitted from this treatment were then enrolled in the long-term analysis that were presented at ASH.

Patients remained on this targeted therapy for a median of 11.1 months. Nearly a third of patients remained on treatment for at least two years, with about half of those remaining continuing treatment for four years or more.

No new toxicities were seen in patients, which Rule considered encouraging. However, patients experienced grade 3 or higher side effects such as neutropenia (17%), pneumonia (13.5%), atrial fibrillation (5.7%) and dyspnea (4.3%). Additionally, 11.4% of patients developed secondary malignancies, which were primarily nonmelanoma skin cancer.

The median progression-free survival (PFS) was 12.5 months with Imbruvica compared with a median PFS of 10.9 months with each patient’s most recent prior line of therapy. The researchers also noted that 27% of patients remained progression-free for one year or longer than they did with their prior regimen.

“With MCL, when you use chemotherapy, each time you use a different kind of chemotherapy, you get less of a response,” said Rule. “This is a common complication with lymphomas. With MCL when using ibrutinib, we find that ibrutinib responses are generally better compared with the prior therapy.”

In terms of what next steps will be taken as a result of these findings, Rule noted that more research is needed.

“It’s clear that the earlier we use the drug, the better the outcome,” he said. “The next steps are using the drugs upfront.”

Rule is currently running a trial in United Kingdom comparing the frontline combination of Imbruvica and Rituxan (rituximab) to chemotherapy in older patients. “This trial will tell us whether it’s better than chemotherapy,” Rule explained.

“It is very clear that early use of drug combinations is the way we are going to be going with this disease, and chemotherapy may very well become a thing of the past.”

A version of this article previously appeared on OncLive® as “Rule Highlights Continued Benefit with Ibrutinib in Relapsed-Refractory MCL”