For patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who are 70 years of age or younger, initial therapy with a combination of ibrutinib and rituximab (IR) showed superior efficacy over chemoimmunotherapy (CIT) in a recent trial. The study results were published in The New England Journal of Medicine.
In the phase 3 E1912 trial (ClinicalTrials.gov Identifier: NCT02048813), treatment-naive patients aged 70 years or younger with CLL or SLL were randomly assigned to receive either IR (354 patients) or CIT (175 patients). CIT in this study consisted of 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR).
Patients in the IR group received an initial cycle of ibrutinib alone, followed by 6 cycles of IR and then continuation with ibrutinib until an occurrence of disease progression. Progression-free survival (PFS) was the primary study end point.
The median follow-up duration was 33.6 months, at which time 78.8% of patients in the IR group remained on ibrutinib treatment. The 3-year PFS rate for patients on IR was 89.4%, compared with 72.9% for patients receiving FCR (hazard ratio [HR], 0.35; 95% CI, 0.22-0.56; P <.001). IR also outperformed FCR for PFS in several preplanned high-risk subgroup analyses, including for patients with unmutated immunoglobulin heavy chain variable region status.
Overall survival (OS) was significantly more favorable with IR. The 3-year OS rate for patients given IR was 98.8%. For patients receiving FCR, the 3-year OS rate was 91.5% (HR, 0.17; 95% CI, 0.05-0.54; P <.001).
Overall, adverse events at grade 3 or above occurred at a similar rate in each treatment group (80.1% with IR vs 79.7% with FCR; P =.91), but they differed in type. Patients who received FCR showed significantly higher rates of grade 3 or 4 neutropenia and infectious complications. Grade 3 or 4 hypertension appeared significantly more frequently in patients who received IR.
The researchers concluded that IR demonstrated superior PFS and OS results compared with the standard FCR therapy for this patient population.
- Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia [published online August 1, 2019]. N Engl J Med. doi:10.1056/NEJMoa1817073