Paul Barr, MD: Options to Prolong Survival

What options might you consider to prolong survival in this patient?

This patient is not that old but does have significant comorbidities and, as a result, has fewer treatment options available to him. We want to use our most effective agents, the ones that have provided an OS benefit.

One I mentioned previously, ibrutinib, in the Resonate trial did, where ibrutinib was compared to the anti-CD20 antibody ofatumumab. We did see an OS benefit for ibrutinib. Another option where we’ve seen an OS benefit is idelalisib plus rituximab. This was compared in a randomized trial to single-agent rituximab. In essence, patients with a short duration of remission and significant comorbidities having relapsed CLL were enrolled to either a, a course of idelalisib given twice a day plus rituximab, or placebo plus rituximab. Similar to the Resonate trial, we saw an improvement in PFS at a very early time point, but also an OS benefit for the doublet, the idelalisib-rituximab strategy.

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.