Results demonstrate ibrutinib’s potential as a new standard of care
Abstract: LBA-4 A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912)
Results: In a late-breaking abstracts session, researchers presented the results of a trial of the ECOG-ACRIN Cancer Research Group in which a randomized group of patients received either ibrutinib and rituximab (IR) or fludarabine, cyclophosphamide, and rituximab (FCR) in a 2:1 ratio. After a median follow up of 33.6 months, the IR combination demonstrated superior progression-free survival (PFS) and overall survival (OS) compared to the FCR combination. Patients receiving the IR combination also experienced fewer severe events.
Abstract: 6 Ibrutinib Alone or in Combination with Rituximab Produces Superior Progression Free Survival (PFS) Compared with Bendamustine Plus Rituximab in Untreated Older Patients with Chronic Lymphocytic Leukemia (CLL): Results of Alliance North American Intergroup Study A041202Clinically Relevant Abstract
Results: The 547 patients, who were 67 percent male and a median age of 71, were randomized into bendamustine and rituximab (BR), ibrutinib, or a combination of ibrutinib plus rituximab, to determine whether ibrutinib-containing regimens are superior to chemoimmunotherapy (CIT) in terms of PFS.
While the median OS was not reached in any study arm and was similar across treatment groups, ibrutinib produced superior PFS to standard CIT, and the addition of rituximab did not add incremental benefit to ibrutinib. The toxicity and cost of ibrutinib justify future efforts to reduce the need for long-term continuous treatment.
Implications: These results demonstrate that the standard of care for treating CLL patients has essentially shifted from chemoimmunotherapy to an ibrutinib-based therapy. The ibrutinib plus rituximab combination proved more effective than chemoimmunotherapy whether treating older or young patients. A very small subset of patients, approximately 10-15 percent (those with mutated IgHV), remain chemoimmunotherapy candidates. Questions remain as to whether the addition of rituximab to ibrutinib is needed, or if the results seen in this trial could have been achieved with ibrutinib alone, as the study suggests. It is estimated that ibrutinib will be a front-line therapy in nearly 90 percent of CLL patients going forward. Future research is needed to determine whether treatment is needed until disease progression or if treatment can be delivered for a set period of time, mitigating costs and potential adverse events.