Chemo-Free Ibrutinib and Rituximab Show Promising Activity in Older Patients with MCL

A chemotherapy-free combination regimen consisting of ibrutinib and rituximab (IR) produced high response rates and promising survival outcomes in previously untreated older patients with high-risk mantle cell lymphoma (MCL), according to results from a phase II trial presented at the 62nd American Society of Hematology Annual Meeting & Exposition.

According to author Preetesh Jain, MD, of the University of Texas MD Anderson Cancer Center, older patients with MCL often have poor functional status and are ineligible for intensive chemo-immunotherapy or hematopoietic cell transplantation. In contrast, chemotherapy-free therapies may provide a significant advantage in these patients.

In their study, Dr. Jain and colleagues administered daily oral ibrutinib 560 mg for 28 days in 50 patients with MCL aged 65 to 84 years. Rituximab 375 mg/m2 was administered on certain days during cycle one, followed by rituximab infusion on day one of every cycle for cycles three through eight. After cycle eight, the investigators gave patients rituximab on day one every two months for up to two years.

At the last follow-up, 24 patients remained on the study therapy. Approximately 34% of the overall population developed atrial fibrillation (AF), with a median time of onset of 9.4 months. Therapy discontinuation was associated with AF (n=10), disease progression (n=4), bleeding (n=4), infections (n=2), myocardial infarction (n=1), hypertension (n=1), chest pain (n=1), colitis (n=1), joint pains (n=1), esophageal cancer (n=1), and patient choice (n=1).

“The increased incidence of arrhythmia observed in our study is likely due to high number of cardiovascular risk factors in this population,” the researchers explained. “This suggests that baseline cardiac evaluation and cardiovascular risk factor modification should be added to IR therapy.”

Over the median follow up of 36.2 months, a total of four patients progressed after taking IR for four, nine, 13, and 33 months. Two patients died.

Among patients evaluable for response, the best overall response rate (ORR) was 96%. In addition, the ORR and complete response (CR) rates for patients who developed AF (n=17) were 76% and 47%, respectively. In contrast, the ORR was 97% and CR was 70% in patients who did not develop AF (n=33).

The overall median progression-free survival (PFS) and OS were not reached at time of data cutoff. Patients who achieved CR, however, demonstrated a trend of longer PFS and OS versus patients who did not experience a CR.