Updated Management of Chronic Lymphocytic Leukemia

Alice Goodman

October 2014, Vol 5 , No 8 - NCCN Congress Highlights


New York, NY—The FDA approvals of obinutuzumab (Gazyva), ofatumumab (Arzerra), ibrutinib (Imbruvica), and idelalisib (Zydelig) have changed the treatment paradigm of patients with chronic lymphocytic leukemia (CLL).

William G. Wierda, MD, PhD, Medical Director, Department of Leukemia, M.D. Anderson Cancer Center, Houston, discussed where these new drugs fit into the treatment algorithm at the 2014 National Comprehensive Cancer Network Congress.

The first-line treatment of asymptomatic early-stage CLL remains watch and wait.

For symptomatic patients with CLL, important considerations in selecting first-line treatment include age, comorbidities, and cytogenetics. The standard of care for younger patients with good performance status includes fludarabine, cyclophosphamide, and rituximab; bendamustine and rituximab; and fludarabine plus rituximab. For elderly frail patients, the current standard of care for front-line therapy includes chlorambucil plus obinutuzumab or chlorambucil plus ofatumumab; ibrutinib is a good choice for patients with 17p deletions.

“Patients with deletions in 17p were previously untreatable. I’m happy to have this option,” Dr Wierda said.

Elderly Patients
In a recent study (Goede V, et al. N Engl J Med. 2014;370:1101-1110), obinutuzumab plus chlorambucil achieved significantly improved progression-free survival (PFS) compared with rituximab plus chlorambucil (26.7 months vs 16.3 months, respectively; P <.001), establishing this combination as a standard of care in elderly patients. Currently, there is no significant overall survival benefit.

“Beware of infusion-related reactions and some myelosuppression” with obinutuzumab, Dr Wierda said.

A separate study, COMPLEMENT-1, which was presented at the 2013 American Society of Hematology meeting by Hillmen and colleagues, showed that ofatumumab plus chlorambucil was significantly superior to chlorambucil for PFS as up-front therapy in older patients with comorbidities, establishing this combination as a standard as well.

Ibrutinib
Much has been written about ibrutinib, an oral Bruton’s tyrosine kinase inhibitor, and studies in CLL have shown improved outcomes with this agent.

After treatment with ibrutinib is initiated, there is a transient elevation in lymphocyte count (lymphocytosis), but with continued treatment, a dramatic reduction in lymph node size is observed. The majority of patients treated with ibrutinib respond, including treatment-naïve patients and patients with relapsed/refractory disease. Over time, patients with lymphocytosis convert to complete response, Dr Wierda said.

Ibrutinib is very safe, he emphasized, with a low frequency of grade ?3 adverse events. The 30-month PFS rates are 96.3% in treatment-naïve patients and 68.4% in patients with relapsed/refractory disease.

“PFS of 90% at 3 years is unheard of,” Dr Wierda noted.

The PFS rates with ibrutinib at 30 months in patients with relapsed/refractory disease stratified by cytogenetics were 45.9% in patients with 17p deletions, 74.2% in those with 11q deletions, and 89% in patients with neither abnormality.

“There is no question that ibrutinib is the treatment of choice for relapsed patients with no 17p or 11q deletions,” Dr Wierda said. “Even with this new agent, the risk is high in those with 17p deletions. Consider these high-risk patients for transplant,” he said.