Optimizing Targeted Therapy in IgVH-Unmutated CLL - Episode 4

Ibrutinib's Role in Treating IgVH-Unmutated CLL

William Wierda, MD, PhD:For this particular patient, the choice of treatment was ibrutinib monotherapy. Ibrutinib is currently approved in the United States for both previously untreated patients as well as previously treated patients. The particular choice of ibrutinib for this patient is driven predominantly by the presence of the 17p deletion because we know that chemoimmunotherapy exposure and chemoimmunotherapy treatment for patients who have 17p deletion are really contraindicated. It’s not active or effective at getting long-term control of the disease, so for this patient, the particular choice was based on the presence of the 17p deletion.

There are somewhat limited data available for treatment of patients with CLL in the frontline setting with 17p with ibrutinib. We have some information, but not a lot of patients have been treated in clinical trial, in this setting. A 17p deletion is an unusual or infrequent characteristic in untreated patients to begin with—about 5% of untreated patients. In terms of the clinical trial data we have, there are fewer patients who have been reported on with 17p deletion in the frontline setting treated with ibrutinib.

The expectation for this patient is an extended period of durable disease control and remission. Most of the patients who are receiving ibrutinib in the frontline setting and in the salvage setting have a response. Nearly all of them have responses. Most of the responders are partial responders where the disease burden is reduced by at least 50% or more. A fewer percentage of them achieve a complete remission. This patient particularly achieved a complete remission, which is a very favorable feature for the response for this patient and would likely be associated with a long period of disease control with ibrutinib.

For such patients, we aren’t necessarily stopping treatment even if they achieve a complete remission. It would be reasonable to have an assessment of minimal residual disease in this patient to determine whether there is any measurable disease for the patient. I would expect that that’s not the case. It would be highly, highly unusual to have a patient with a 17p deletion getting ibrutinib in the frontline setting achieving a complete remission and to be MRD-negative. That’s a very rare event. This patient has had a very good response, and the expectation should be that they have several years of disease control with the ibrutinib monotherapy.

We have done a trial at MD Anderson looking at ibrutinib with and without rituximab. Chemotherapy works much better when you give a CD20 antibody with it. That doesn’t seem to be so much the case with ibrutinib-based therapy. In our experience, and in our trial that we did—a randomized trial of ibrutinib with or without rituximab—there wasn’t really a benefit in terms of long-term outcome with the addition of rituximab to ibrutinib for patients treated for relapsed disease. However, there were a few patients in the frontline cohort of our trial who did have 17p deletion.

Transcript edited for clarity.

A 58-Year Old Female with IgVH-Unmutetd CLL

  • A 58-year-old female with incidentally noted lymphocytosis on routine
  • PMH: hypercholesterolemia managed on simvistatin, mild osteoarthritis
  • PE: 1.0-cm cervical node, no palpable spleen or liver
  • PS, ECOG 0
  • Laboratory findings:
    • WBC; 45 X 109/L, 85% lymphocytes
    • Lymphocytes; 86.2 X 109/L
    • Hb; 13.9 g/dL
    • Platelets; 274 X 109/L
    • ANC; 1,950/mm3
    • LDH 160 U/L
  • Flow cytometry; CD5+, CD19+, CD20+(dim), CD23+, slg+ (dim), ZAP70+
  • Cytogenetics by FISH; del(17p), trisomy 12, IgVH unmutated
  • β2M, 3.6 mg/L
  • BM biopsy; 70% lymphocytes, diffuse pattern
  • Diagnosis; chronic lymphocytic leukemia
  • Observed for over 2 years, then developed progressive sever fatigue and night sweats
  • The patient was treated with ibrutinib and achieved a complete response to therapy after 2 months