The Combination of Alemtuzumab and Ofatumumab in Previously Untreated CLL
Although the current standard chemoimmunotherapy is effective as frontline treatment of CLL, it is poorly tolerated in elderly patients with comorbidities, has potential long-term bone marrow toxicity, and has limited efficacy in high-risk CLL. Thus, immunotherapy alone may offer a less toxic, better-tolerated option for these patients. A previous study of the combination of alemtuzumab and rituximab showed promising results (Frankfurt O, et al. Leuk Lymphoma. 2014 Jun 17. Epub ahead of print). Because ofatumumab has been shown to improve complement-mediated cytotoxicity over rituximab, at ASH 2014, Ma and colleagues reported on a phase 2 study testing the safety and efficacy of the combination of alemtuzumab and ofatumumab for the frontline therapy of CLL (Blood. 2014;124. Abstract 4686).
A total of 31 patients have completed treatment with alemtuzumab plus ofatumumab, 58% of whom were Rai stage III/IV, 48% had unmutated IGVH, and 23% had del17p or TP53 mutation. The ORR was 97%, with 42% complete remissions (CRs) and 55% PRs. Minimal residual disease (MRD) by bone marrow flow cytometry was negative in 12 of the 13 patients achieving a CR and in 4 of the 17 patients achieving a PR. In all, 3 patients required subsequent treatment as a result of progressive disease.
The most frequent treatment-emergent AEs included neutropenia, anemia, thrombocytopenia, alemtuzumab-related local injection-site reaction, ofatumumab-related infusion symptoms, pyrexia, and fatigue. Cytomegalovirus reactivation occurred in 16 cases and was successfully treated with antiviral therapy. Although some patients experienced grade 3/4 neutropenia or thrombocytopenia, cytopenia could be avoided or lessened by stopping alemtuzumab once MRD was achieved in the bone marrow.
These results suggest that the combination of alemtuzumab plus ofatumumab produces high response rates as first-line therapy in patients with CLL, including MRD-negative CR, and has an acceptable safety profile, especially if therapy is stopped after achieving CR/MRD negativity.