Treating Younger and Older Patients With CLL

Cytogenetic risk assessment, immunoglobulin variable region heavy chain (IgVH) mutations, age, and performance status should all be considered when determining which treatment to utilized for patients with newly diagnosed chronic lymphocytic leukemia (CLL), says Javier Pinilla-Ibarz, MD, PhD.

Younger patients with low-risk cytogenetics and IgVH mutations tend to perform well 7 years after treatment with fludarabine, cyclophosphamide, and rituximab (FCR). The FCR regimen yields a complete remission rate of about 70%, with median progression-free survival (PFS) of 6 to 7 years, states William Wierda, MD, PhD.

Long-term follow-up data from MD Anderson Cancer Center and the German CLL Study Group reveal a plateau in the PFS curve for FCR at 10 years, explains Jennifer Brown, MD, PhD. Nearly 40% of patients are still in remission, with many still minimal residual disease (MRD)-negative, suggesting that a subset of patients may actually be cured by FCR.

Younger patients with robust performance status comprise only one quarter of the CLL population, notes Pinilla-Ibarz. In general, most patients are over 65 years old will have multiple comorbid conditions that preclude them from receiving FCR. In these patients, bendamustine plus rituximab is a reasonable treatment option, since it causes less myelosuppression than FCR. Incorporating other monoclonal antibodies, such as obinutuzumab or ofatumumab, offer additional benefit for patients who are otherwise not eligible for intensive chemo-immunotherapy approaches.

While the age of 65 has been used as a general cutoff point between the elderly and younger populations, it is a flexible guideline, comments Wierda. Each patient should be assessed individually to confirm their fitness level and comorbities. Wierda’s practice has considered patients who are 70 years old, but physiologically younger than 65 years, for more aggressive treatments.

Patients with 17p deletion or a TP53 mutation are oftentimes refractory to fludarabine or other conventional chemotherapy regimens. The standard of care for patients with a 17p deletion, regardless of age, is ibrutinib, an inhibitor of the B-cell receptor.