New Drug Approvals Bring Hope, Challenges in the Treatment of Chronic Leukemia
The approvals of obinutuzumab, ibrutinib, and idelalisib provide clinicians with new treatment options for patients with CLL.
The paradigm of the treatment of chronic lymphocytic leukemia (CLL) has shifted, with the recent addition of obinutuzumab, idelalisib, and ibrutinib to the armamentarium.
“These agents underscore our advancement in the understanding of the biology of CLL and will improve outcomes for many patients with CLL,” wrote David S. Sanford, MD, of The University of Texas MD Anderson Cancer Center in Houston, TX, and colleagues in Clinical Lymphoma, Myeloma, and Leukemia.1
Approved by the U.S. Food and Drug Administration (FDA) in November 2013 in combination with chlorambucil for treatment-naïve patients with CLL, obinutuzumab is a humanized type II immunoglobulin G1 antibody that targets CD20. Its cytotoxic effect is likely a result of antibody-dependent cell-mediated toxicity.2
The front-line efficacy was demonstrated in the randomized, open-label, phase 3 CLL11 trial, in which obinutuzumab plus chlorambucil resulted in greater complete (20.7% vs. 7.0%) and molecular response rates compared with rituximab plus chlorambucil.3
In addition, treatment with chlorambucil resulted in a prolonged median progression-free survival (PFS) of 26.7 months compared with 16.3 months in the rituximab plus chlorambucil arm (hazard ratio [HR], 0.44; 95% CI, 0.34 to 0.57; P<0.001) and 11.1 months in the chlorambucil monotherapy arm (HR, 0.18; 95% CI, 0.13 to 0.24; P<0.001).
In addition, overall survival (OS) was significantly greater in the obinutuzumab arm compared with chlorambucil monotherapy (HR, 0.41; 95% CI, 0.23 to 0.74; P=0.002), but was not significant compared with the rituximab arm (HR, 0.66; 95% CI, 0.41 to 1.06; P=0.08).
Median OS has not yet been reached. However, the improved efficacy with obinutuzumab did not carry over to patients with 17p deletion.
The addition of obinutuzumab did result in greater rates of adverse events (AEs) including grade 3 to 4 neutropenia and thrombocytopenia, but rates of infection were similar compared with the addition of rituximab.3
In addition, 20% of patients experienced infusion-site reactions during their first infusion of obinutuzumab, compared with 4% of patients who received rituximab.
Furthermore, patients in the obinutuzumab arm were more likely to discontinue therapy compared with the rituximab or chlorambucil monotherapy arms.