Paul Barr, MD: Treatment Options for Patients With Previously Treated CLL

What are the principle treatment options in this patient with previously treated CLL?

We have a laundry list of treatment options in patients who have been previously treated for CLL. But in this patient, who is not terribly old but has significant comorbidities, it’s important to consider what the patient has previously been treated with, what poor prognostic markers he’s displaying, [and] what the goals of treatment are. This is where the art of oncology comes in, trying to figure out what’s best from that laundry list. A time-to-progression of only 1 year after first-line chemoimmunotherapy is important.

In this particular patient we really need to get good disease control. We need to use a strategy that’s probably separate from our typical chemoimmunotherapy options, [including] an allogeneic stem cell transplant. I worry that we would take too many risks in such a strategy. So for this particular patient I’m thinking of the BCR signaling agents, notably ibrutinib. Idelalisib/rituximab is another good option for this patient. I’m [also] thinking of clinical trials for such a patient, and some of the investigational agents such as the Bcl-2 inhibitor venetoclax, that’s a very important option, as well as other novel agents.

Case 2: Relapsed and Refractory CLL

James S. is a 67-year-old college professor from Ithaca, New York; he is a Vietnam veteran with a history of treatment for Agent Orange exposure; his history is also notable for prior smoking (15-pack year) and mild COPD.

In November 2013, he presented to his PCP for a routine physical; his examination showed mild lymphadenopathy and his CBC showed evidence of lymphocytosis (lymphocytes 6 x 109/L); he was referred to an oncologist for further diagnostic evaluation.

Differential diagnosis showed B-cell CLL, with absolute lymphocytosis (19,000/mm3) and flow cytometry positive for CD5 and CD23.

Interphase cytogenetic analysis showed no deletion of 17p.

The oncologist initiates treatment with bendamustine/rituximab (BR) and James shows improvement in hematologic parameters after 6 cycles.

James was out of the country at a meeting, and he failed to return for a scheduled follow-up appointment in January 2015.

In March 2015, he presented to his oncologist with symptoms of unintentional weight loss over the past 2 months (>10%), severe fatigue (interfering with work), and dyspnea; his CBC is consistent with worsening anemia and thrombocytopenia.

CT scan shows evidence of extensive abdominal lymph node recurrence.

At the time of his recurrence, James’s ECOG performance status was 2, and liver and kidney functioning were within normal limits.