Combining AbbVie’s Imbruvica (ibrutinib) with Treanda (bendamustine) and Rituxan (rituximab) improves long-term survival outcomes in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) whose cancer reappeared or failed to respond to prior chemotherapy, long-term data from a Phase 3 trial shows.
Continuing Imbruvica as a single therapy after the triple combo also helps delay cancer progression in these patients, according to the data.
Trial results were reported in the study, “Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma,” published in the journal Leukemia.
The report describes the updated, long-term follow-up results from the Phase 3 HELIOS trial (NCT01611090), a randomized, double-blind, placebo-controlled study, evaluating treatment with a combination of Imbruvica, Treanda, and Rituxan for CLL/SLL after prior therapies.
The study enrolled 578 patients whose cancer came back (relapsed) or was resistant (refractory) after at least one prior line of chemotherapy. Patients with a 17p deletion, a mutation associated with high-risk disease, were not included.
Participants were randomly assigned to receive either daily Imbruvica (420 mg) or placebo, in combination with 28-day cycles of Treanda plus Rituxan (maximum of six cycles). At the end of the Treanda-Rituxan cycles, patients remained on daily Imbruvica or placebo alone. The median follow-up time was 34.8 months.
Consistent with the primary analysis findings and prior long-term data at a median of 25.4 months, Imbruvica favored long-term survival compared with the placebo.
At 36 months, 68% of patients taking Imbruvica survived without cancer regrowth, known as progression-free survival, versus 13.9% patients on the placebo.
These figures translated into triple therapy-treated patients having a 79.4% less chance of seeing their cancer progressing or dying over those receiving placebo. Additionally, overall survival was 34.8% higher for those on Imbruvica.
Accordingly, the triple combo deepened patients’ response to therapy, leading to stronger reductions in cancer cell load, or a stronger cancer remission.
Reflecting this effect, 26.3% of patients taking Imbruvica were cleared of minimal residual disease, meaning their cancer cells were lowered to levels undetectable by very sensitive techniques, versus 6.2% of those on placebo.
The profile of treatment-emergent adverse events “was similar to the initial analysis when treatment extended beyond 17 months and was comparable with the safety profile reported in other clinical trials of ibrutinib in CLL patients,” the researchers wrote.
Serious adverse events occurred in 61.3% of the patients on Imbruvica, the most common being pneumonia (13.6%) and febrile neutropenia (10.1%), meaning low blood counts of neutrophils, a type of white blood cell. In the Imbruvica-treated group, 28 (9.8%) patients died as a result of adverse events, mainly infections.
The HELIOS data supports that “an induction-type period of ibrutinib+BR [Imbruvica plus Treanda-Rituxan] therapy followed by continued ibrutinib treatment produces better responses than BR therapy alone and improves outcomes as the duration of therapy increases,” the researchers said.
The extended follow-up data reported in the current study confirmed that the positive effects “of continuing ibrutinib following ibrutinib+BR are maintained irrespective of the number of prior lines of therapy or the presence of poor prognostic factors,” according to them.
They also emphasized that continued Imbruvica monotherapy following the end of the Treanda-Rituxan cycles “results in continuing improvement in the depth of remission.”