Researchers conducted a phase 3 trial to determine if ibrutinib/rituximab compared with standard chemoimmunotherapy (fludarabine/cyclophosphamide/rituximab) is more effective at treating patients with treatment-naive chronic lymphocytic leukemia (CLL) and found that ibrutinib/rituximab increased progression-free survival and overall survival compared with standard chemoimmunotherapy.
One of the most common lymphoid cancers in adults, CLL starts in white blood cells called lymphocytes in the bone marrow. Usually, this cancer progresses slowly; eventually, cancerous cells grow and spread to other parts of the body.
In this phase 3 trial, published in New England Journal of Medicine, 529 patients were randomly assigned in a 2:1 ratio to receive either ibrutinib plus rituximab for six cycles, after completing a single cycle of ibrutinib monotherapy, followed by ibrutinib until disease progression or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. To be eligible, patients had to be 70 years or younger with previously untreated CLL.
After a median follow-up of 33.6 months, ibrutinib/rituximab was associated with an increased progression-free survival compared with standard chemoimmunotherapy (89.4% vs 72.9%). For patients without immunoglobulin heavy-chain variable region (IGHV) mutation, the ibrutinib/rituximab combination achieved a better progression-free survival compared with chemoimmunotherapy (90.7% vs 62.5%).
The most common treatment-related adverse events of grade 3 or higher in the ibrutinib/rituximab group included lymphocyte count increase, hypertension, leukocytosis, neutropenia, and infection. Lymphocyte count decrease, neutropenia, white-cell count decrease, and febrile neutropenia were the most common side effects for the chemoimmunotherapy group.
Additional research needs to be conducted to combat ibrutinib drug toxicities and resistance. Study authors warn, "…indefinite use of ibrutinib therapy has been associated with substantial expense and the potential for long-term toxic effects and may increase the risk of clonal selection leading to drug resistance."
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