Ibrutinib combination confers significant benefit in relapsed CLL

CHICAGO – The addition of ibrutinib to bendamustine and rituximab conferred an 80% reduction in the risk for progression or death in patients with previously treated chronic lymphocytic leukemia, according to the interim results of a phase 3 study presented at the ASCO Annual Meeting.

Perspective from Stefan Barta, MD

“CLL is an incurable disease, and every single patient will relapse,” Asher Alban Chanan-Khan, MD, professor of medicine and chair of hematology and oncology at the Mayo Clinic in Jacksonville, Florida, told HemOnc Today. “For the first time, we have developed this drug which is showing survival benefits, improving patients’ chances of going into remission and which can partner [with existing therapies] – or act by itself – to deliver such significant responses without significant toxicity.”

CLL is treated with chemotherapy and targeted therapies; however, these methods are not curative and all patients become treatment-resistant over time, according to study background.

Chanan-Khan and colleagues evaluated data from 578 patients (median age, 64 years) with previously treated CLL or small lymphocytic lymphoma in the randomized, phase 3 HELIOS study. Thirty-eight percent of patients had Rai Stage III/IV disease, and patients had received a median of two prior therapies.

Researchers assigned patients to receive up to six cycles of bendamustine (Treanda, Cephalon) and rituximab (Rituxan, Genentech/Biogen Idec) plus 420 mg daily ibrutinib (Imbruvica, Pharmacyclics; n = 289) or placebo (n = 289).

PFS served as the primary endpoint. OS and overall response rate (ORR) served as secondary endpoints.

Median follow-up was 17.2 months.

Researchers observed a significantly prolonged median PFS in the ibrutinib arm compared with the placebo arm (not reached vs. 13.3 months; HR = 0.2; 95% CI, 0.15-0.27). These data equated to an 80% reduction in the risk for progression or death with the ibrutinib combination compared with placebo.

ORR (82.7% vs. 67.8%; P < .0001) and complete response rates (10.4% vs. 2.8%) also improved in the ibrutinib arm.

Median OS had not been reached at the time of the analysis.

Due to the positive results, researchers allowed 31% (n = 90) of patients with progressive disease to cross over from the placebo arm to the ibrutinib arm.

Researchers observed similar rates for adverse events between arms. Neutropenia (ibrutinib, 58.2% vs. placebo, 54.7%) and nausea (36.9% vs. 35.2%) were the most common all-grade adverse events. Patients in the ibrutinib and placebo arms also demonstrated similar rates for grade 3 to grade 4 neutropenia (53.7% vs. 50.5%) and thrombocytopenia (15% for both). Patients in each arm also experienced grade 3 to grade 4 atrial fibrillation (2.8% vs. 0.7%) and major hemorrhage, defined as serious or grade 3 or worse events (3.8% vs. 1.7%).

Fewer patients in the ibrutinib arm experienced fatigue compared with patients in the placebo arm.

“This is truly a blessing for patients,” Chanan-Khan said. “People are living longer, and their chance of getting into remission is higher than if they were just getting chemotherapy, and they are having a better quality of life.” – by Cameron Kelsall

Reference:

Chanan-Khan AA, et al. Abstract LBA7005. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

For more information:

Asher Alban Chanan-Khan, MD, can be reached at the Mayo Clinic, 4500 San Pablo Road S, Jacksonville, Fla 32224; e-mail: chanan-khan.asher@mayo.edu.

Disclosure: The study was funded by Janssen R&D. Chanan-Khan reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

Perspective

Stefan Barta, MD

It’s unclear whether ibrutinib was given as maintenance after bendamustine and rituximab chemotherapy. Clearly ibrutinib is an active agent. Currently there is an ongoing trial looking at ibrutinib alone vs. ibrutinib plus bendamustine and rituximab vs. rituximab and ibrutinib (ALLIANCE). Outcomes of this trial will show whether combining ibrutinib with other agents is superior to ibrutinib by itself.

Stefan Barta, MD

Fox Chase Cancer Center

Disclosures: Barta reports no relevant financial disclosures