Ibrutinib Regimens Have Superior PFS Compared With Chemoimmunotherapy in Older Patients With Untreated CLL

Ibrutinib-containing regimens have similar overall survival (OS) rates but significantly higher progression-free survival (PFS) rates at 2 years compared with bendamustine plus rituximab, according to the results of a study published in New England Journal of Medicine.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and has been treated with chemoimmunotherapy such as chlorambucil plus obinutuzumab or bendamustine plus rituximab. The downside to these treatments are the many toxicities involved, especially in the elderly population. Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib, are a relatively newer drug class that work through B-cell receptor signaling. Because BTK inhibitors have acceptable toxicity and efficacy profiles, many investigators wonder where they stand relative to standard chemoimmunotherapy. The researchers compared chemoimmunotherapy with bendamustine and rituximab with ibrutinib alone and ibrutinib plus rituximab to determine if treatment with ibrutinib is superior to chemoimmunotherapy and if rituximab adds increased efficacy to ibrutinib.

The population that the study targeted were elderly patients, aged 65 years or older, with untreated CLL, patients who are most likely at risk from the toxic effects of chemoimmunotherapy. PFS at 2 years was greater with both ibrutinib arms (87% for ibrutinib and 88% for ibrutinib plus rituximab) compared with bendamustine plus rituximab (74%). Patients on ibrutinib also were 61% less likely to have disease progression compared with bendamustine plus rituximab (HR, 0.39; 95% CI, 0.26-0.58; P <.001). Patients on ibrutinib and rituximab had similar benefits (HR, 0.38; 95% CI, 0.25-0.59; P <.001).

Response rates were also lower with bendamustine plus rituximab (81%) compared with ibrutinib (93%) and ibrutinib plus rituximab (94%). However, bendamustine plus rituximab did have higher complete remission rates than either ibrutinib or ibrutinib plus rituximab (26% vs 7% vs 12%, respectively), as well as a higher percentage of patients with undetectable minimal residual disease (8% vs 1% vs 4%, respectively). Although ibrutinib had significantly higher PFS percentages at 2 years, it did not improve overall survival (OS) compared with chemoimmunotherapy. At 2 years, the OS for bendamustine plus rituximab was 95%, compared with 90% for ibrutinib and 94% for ibrutinib plus rituximab (P ≥.65).

Serious adverse events (AEs, grade 3-5) that were hematologic occurred more frequently with bendamustine plus rituximab (61%) than either ibrutinib (41%) or ibrutinib plus rituximab (39%). Nonhematologic AEs occurred more frequently in the ibrutinib-containing regimens (74% for each arm) than bendamustine plus rituximab (63%). Atrial fibrillation and hypertension also occurred more frequently in the ibrutinib arms compared with chemoimmunotherapy.

From this study, investigators concluded that there was a PFS benefit in using ibrutinib compared with bendamustine plus rituximab. For patients who are at high risk of developing AEs from chemoimmunotherapy, ibrutinib-containing regimens should be considered.

Reference

Woyach JA, Rupper AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. [published online December 1, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1812836.