Dr. Wierda: When you're considering treatment for patients with CLL, there are a couple of features that need to be highlighted with this disease specifically. That is, that most of the patients are elderly. These patients don't tolerate the myelosuppressive regimens as well as their younger counterparts, so purine analogs are challenging to give them. Alkylating agents are also challenging to give them.
They tend to have more toxicity. And I think there's an underappreciated renal insufficiency in the elderly population. You don't get a good idea about [it] by just looking at their creatinine. Fludarabine is renally cleared, and I think we most likely will overdose patients with
In terms of thinking about age and comorbidities, in the US, we generally use age as sort of a surrogate marker of how they'll be able to tolerate treatment and as a correlate with their comorbidities.
My general rule of thumb is that I use 70 [years] as a cutoff for identifying patients who are more or less likely to be able to tolerate myelosuppression, rather than using 65 [years]. So a patient who's 67 [years old] would be a patient that I would be considering a chemoimmunotherapy regimen such as FCR [fludarabine-cyclophosphamide-rituximab] as their
If a patient is over 70 [years], then I'm less likely to be considering an
For people between 65 and 70 [years], I might dose-reduce them, depending on what their blood counts are before I start treatment. But, certainly, for individuals younger than 70, FCR would be my front-line therapy.
Narrator: Purine-analog–based chemotherapy plus rituximab, such as FCR, FR [fludarabine-rituximab], or PCR [pentostatin-cyclophosphamide-rituximab], is preferred for younger patients and for those older patients who are able to tolerate or who require more aggressive therapy. However, other options are recommended for patients aged 70 or older—or younger patients with significant comorbidities. These include chlorambucil with or without rituximab, bendamustine with or without rituximab, fludarabine with or without rituximab, alemtuzumab or rituximab as single agents, lenalidomide, or cladribine.8
Dr. Wierda: There is some suggestion that bendamustine may be a bit better tolerated, including in terms of myelosuppression, that in the
Narrator: Recently, the US Food and Drug Administration approved obinutuzumab for use in combination with chlorambucil to treat patients with previously untreated CLL.10 The approval was based on findings from CLL11, a phase 3, randomized,