A higher complete response rate was seen in patients given both agents compared with those given Imbruvica alone.
Results of a phase 2 clinical trial offer optimism to some patients with mantle cell lymphoma (MCL).
Researchers from Australia found a higher complete response (CR) rate with the combination of Venclexta (venetoclax) and Imbruvica (ibrutinib) in patients with previously untreated or relapsed/refractory MCL than the CR in a historical group of patients who received Imbruvica alone.
The AIM study, published in The New England Journal of Medicine, was conducted at two sites in Melbourne from July 2015 through September 2016 and included 23 patients with relapsed/refractory disease and one with previously untreated MCL. The median age of patients was 68 years.
The median number of previous therapies among relapsed/refractory patients was two. The one previously-untreated patient could not undergo cytotoxic chemotherapy because the patient declined blood transfusions, and expressed both a TP53 mutation and deletion in the lymphoma.
Half of the patients, including the previously untreated patient, had a TP53 aberration, while 75 percent of the patients had a high-risk prognostic score, and 25 percent had an NF-κB pathway mutation.
“TP53 mutations appear to be a critical prognostic factor in mantle cell lymphoma, being strongly associated with treatment resistance and inferior survival among patients receiving intensive chemotherapy and undergoing first-line autologous stem-cell transplantation,” lead author Constantine S. Tam, M.D., Department of Hematology, Peter MacCallum Cancer Centre, Melbourne, and colleagues wrote.
Patients were initially given Imbruvica alone for the first four weeks. Then, patients received Venclexta with dosage increasing weekly based on recommended doses for treating patients with chronic lymphocytic leukemia.
At week 16, the CR rate was 42 percent per CT imaging, which is higher than the CR rate of 9 percent seen at 16 weeks with Imbruvica monotherapy, according to investigators of the study. The findings showed that the CR rate as measured by PET imaging was 62 percent at week 16.
Median progression-free survival (PFS) was not reached after the median follow-up of 15.9 months. The estimated 12-month PFS was 75 percent and 57 percent at 18 months, while at 15 months, 78 percent of patients with a response were estimated to be progression-free.
At the time of analysis, median duration of response was not reached. Investigators found an overall survival rate of 79 percent at 12 months and 74 percent at 18 months.
Overall, eight patients experienced disease progression, five of whom had disease that was primarily refractory to study therapy and three who had a relapse after CR while continuing therapy.
The most commonly reported grade 3 or greater side effects were neutropenia (33 percent), thrombocytopenia (17 percent), anemia (12 percent) and diarrhea (12 percent).
Also, 14 (58 percent) patients experienced serious side effects and six patients died during the study, four of which were due to disease progression. Of the other two deaths, one patient died from a malignant ear infection during week six after treatment with Imbruvica alone and the other died from cardiac failure during ongoing complete response.