Ibrutinib and Other Options for CLL

Ian W. Flinn, MD, PhD:Choice of therapies for any patient, including this patient, is based on a variety of factors. One is the host, the patient’s ability to withstand certain therapies and their tolerance, as well as the underlying factors that are driving the CLL [chronic lymphocytic leukemia]. So this patient, you know, otherwise healthy, sort of a typical age for someone with CLL, being 70, in the mid-70’s after their first relapse, I think this patient is very representative of most patients that we would see with chronic lymphocytic leukemia. And the big factor here, of course, is that he’s had prior ibrutinib, and that’s going to really character … color what you’re going to do next.

So, we have a lot of new data out in this first relapsed setting, especially in patients who’ve had prior treatment with ibrutinib. You know there are a variety of options for this patient, but probably, in my mind, the best would be the combination of venetoclax with rituximab, based on the MURANO data that’s been recently presented and published. So venetoclax being a BCL-2 inhibitor, there’s synergistic activity when you combine it with a CD20.

Now he hasn’t seen chemotherapy. He hasn’t seen bendamustine, rituximab, and this is a potential option for him. I’m a little bit concerned about using that approach, especially in this patient who has progressed after ibrutinib treatment.

Ibrutinib, as a frontline treatment in chronic lymphocytic leukemia, is becoming more and more common. We know from the recent studies presented at the American Society of Hematology meeting, that in a study where ibrutinib was compared to bendamustine, rituximab, and was compared to ibrutinib and rituximab, that this patient’s physician was probably a little bit ahead of their time. The results are really very good. We know that an ibrutinib-containing regiment compared to bendamustine-rituximab produced a superior progression-free survival advantage than using the chemotherapy. Previous studies had compared ibrutinib to relatively less chemotherapy. So, for instance, like chlorambucil, and obviously ibrutinib was superior to those type of regimens, but a more classic regimen with bendamustine-rituximab was commonly used in the community. This study from the intergroup presentation showed that ibrutinib was superior to combination chemotherapy.

The other question that comes up is, should I be combining ibrutinib with rituximab? And we’ve seen previous studies, such as data from … MD Anderson, that calls into question whether ibrutinib with rituximab is really beneficial over ibrutinib alone. Now we have randomized phase III data that show that the addition of rituximab to ibrutinib is not superior to ibrutinib alone. And so I think this patient got very good and very appropriate frontline therapy.

Transcript edited for clarity.

A 71-Year-Old Man With CLL

• A 71-year—old man presented with symptoms of persistent fatigue and weight loss
• PMH: Left axillary lymph node, 1.5 cm X 1.5 cm
• PE: Left axillary lymph node, 1.5 cm X 1.5 cm
• Laboratory findings:
  • WBC, 133,000; 85% lymphocytes (ALC, 68,000 cells/mL)
  • Hb; 11.4 g/dL
  • Platelets; 111 X 10⁹/L
  • ANC; 174/mm³
• Molecular testing:
  • Flow cytometry; CD19++, CD5+, CD20+, CD23++, CD38+
  • IgVHmutated
  • FISH, +12
• β2M, 3.0 mg/L
• Diagnosis; chronic lymphocytic leukemia
• BM biopsy; CLL in 88% of cells
• The patient was treated with ibrutinib and achieved a complete remission within 5 months
• 13 months later, the patient reported extreme fatigue; now with 3.0 X 3.0-cm lymph node
• Laboratory findings:
  • Repeat FISH: remained +12
  • WBC, 225 X 10⁹/L
  • HB, 9.6 g/dL
  • Platelets, 103 X 10⁹/L