Tailoring CLL Treatment to a TTT
Editor's Note: The explosion of new therapies to treat chronic lymphocytic leukemia (CLL) has raised questions about how best to integrate novel agents with proven efficacy into treatment algorithms. Among the novel agents that show great promise are ABT-199, ibrutinib, and obinutuzumab. These agents target relatively specific signaling proteins of CLL cells and their microenvironment. CLL appears to be caused by a complex array of genetic events and is a biologically complex disease. Studies are needed to learn how to combine these drugs and to sequence them to optimize outcomes.
Medscape spoke with Michael Hallek, MD, University of Cologne, Cologne, Germany, who has addressed the issue of sequencing agents in CLL in both a recent article and a presentation at the American Society of Hematology 55th annual meeting.
Medscape: What is the current standard of care for patients with newly diagnosed CLL?
Dr. Hallek: Two thirds of newly diagnosed patients are asymptomatic at diagnosis. Those asymptomatic patients with inactive disease do not need treatment. Instead they are monitored and have blood counts obtained during physical exam every 3-6 months.
Those patients who develop symptoms and are physically fit, or both, are treated with fludarabine/cyclophosphamide/rituximab (FCR) as the standard of care for first-line therapy. It is important that physically fit patients get the best therapy available, regardless of age.
Bendamustine/rituximab (BR) showed promising results as front-line therapy in 117 previously untreated CLL patients, including patients with poor-risk cytogenetics. In that study, BR appeared to be somewhat less active than FCR, with lower CR rates, but was also less myelotoxic. Disappointingly, BR appears to be less efficient compared with FCR, according to results of the CLL10 trial reported at ASH 2013 by Barbara Eichhorst, MD.
A larger percentage of patients with active disease have comorbidities and reduced fitness. Obinutuzumab/chlorambucil is a new standard of care for these patients, based on results of the phase 3 CLL11 trial presented at the Plenary Session at ASH 2013. In that study, obinutuzumab/chlorambucil prolonged survival compared with rituximab/chlorambucil, and the new combination is now FDA-approved for elderly CLL patients with comorbidities.
Medscape:What are the challenges in treatment of newly diagnosed patients?
Dr. Hallek: Despite standard treatments, CLL patients with deletions in 17p or point mutations in p53 do not benefit from most available treatment options. Additionally, patients with early relapse are at increased risk of dying. Novel agents are particularly important for these 2 groups. Also, despite the success of chemoimmunotherapy, a large percentage of patients develop secondary malignancies, mainly in the skin and lung. We think that novel agents may reduce this problem, because they do not cause DNA damage.
Regimens Differ for the Fit and Unfit
Editor's Note: The explosion of new therapies to treat chronic lymphocytic leukemia (CLL) has raised questions about how best to integrate novel agents with proven efficacy into treatment algorithms. Among the novel agents that show great promise are ABT-199, ibrutinib, and obinutuzumab. These agents target relatively specific signaling proteins of CLL cells and their microenvironment. CLL appears to be caused by a complex array of genetic events and is a biologically complex disease. Studies are needed to learn how to combine these drugs and to sequence them to optimize outcomes.
Medscape spoke with Michael Hallek, MD, University of Cologne, Cologne, Germany, who has addressed the issue of sequencing agents in CLL in both a recent article and a presentation at the American Society of Hematology 55th annual meeting.
Medscape: What is the current standard of care for patients with newly diagnosed CLL?
Dr. Hallek: Two thirds of newly diagnosed patients are asymptomatic at diagnosis. Those asymptomatic patients with inactive disease do not need treatment. Instead they are monitored and have blood counts obtained during physical exam every 3-6 months.
Those patients who develop symptoms and are physically fit, or both, are treated with fludarabine/cyclophosphamide/rituximab (FCR) as the standard of care for first-line therapy. It is important that physically fit patients get the best therapy available, regardless of age.
Bendamustine/rituximab (BR) showed promising results as front-line therapy in 117 previously untreated CLL patients, including patients with poor-risk cytogenetics. In that study, BR appeared to be somewhat less active than FCR, with lower CR rates, but was also less myelotoxic. Disappointingly, BR appears to be less efficient compared with FCR, according to results of the CLL10 trial reported at ASH 2013 by Barbara Eichhorst, MD.
A larger percentage of patients with active disease have comorbidities and reduced fitness. Obinutuzumab/chlorambucil is a new standard of care for these patients, based on results of the phase 3 CLL11 trial presented at the Plenary Session at ASH 2013. In that study, obinutuzumab/chlorambucil prolonged survival compared with rituximab/chlorambucil, and the new combination is now FDA-approved for elderly CLL patients with comorbidities.
Medscape:What are the challenges in treatment of newly diagnosed patients?
Dr. Hallek: Despite standard treatments, CLL patients with deletions in 17p or point mutations in p53 do not benefit from most available treatment options. Additionally, patients with early relapse are at increased risk of dying. Novel agents are particularly important for these 2 groups. Also, despite the success of chemoimmunotherapy, a large percentage of patients develop secondary malignancies, mainly in the skin and lung. We think that novel agents may reduce this problem, because they do not cause DNA damage.