Optimizing Targeted Therapy in IgVH-Unmutated CLL - Episode 3

Optimizing Treatment Strategies for Patients With CLL

William Wierda, MD, PhD: There are standard indications that are used to initiate treatment for patients with CLL, and these are indications or criteria that we’ve used for many years. They haven’t changed over the many recent years. The reason they’re used is that there haven’t been any studies that have shown that early treatment changes the outcome or changes survival. Earlier treatment doesn’t improve or prolong survival over waiting until they have an indication for treatment. The indications for treatments are relatively simple. They are disease-related symptoms that need to go away when patients are treated effectively. Those are usually night sweats, fatigue, unintentional weight loss, and/or sometimes fever without any evidence of infection. The symptoms can be a trigger and are important, generally speaking, for patients who have lower-stage or earlier-stage disease.

The other indications for treatment are progressive anemia, and I usually use a hemoglobin of 10 or a progressive thrombocytopenia where I usually use a platelet count of 100,000, realizing that the blood counts can fluctuate. I usually don’t select to treatment based on just 1 determination. I will usually repeat the labs after a month or two to confirm that the hemoglobin is in fact below 10 and/or the platelet count is consistently below 100,000 before I will initiate treatment.

In terms of goals of treatment, I think a lot of the discussion lately has been particularly for the older patient population. This includes explaining what the goals of therapy are and clarifying the goals of therapy for that patient group because there are options to manage those patients. The goals can include deep remission with a treatment-free interval. This is a goal that is typically achieved with chemoimmunotherapy, where patients will get a defined course of treatment. There are a variety of chemoimmunotherapy regimens that have been evaluated and are effective, such as chlorambucil plus obinutuzumab or bendamustine plus rituximab. In this strategy, patients receive a defined treatment period of 6 months to a year of chemoimmunotherapy. Typically, they’ll go into remission and have a period of remission that is generally between 2 and 4 or 5 years where they don’t need any treatment. Rather, they’re just getting follow-up. They do relatively well during that remission period. Eventually the disease is likely to come back and need retreatment.

The other strategy and goal is disease control. In this situation, patients are treated with the small molecule inhibitors, including drugs like ibrutinib, where they go on treatment and it’s highly effective. Particularly ibrutinib is highly effective at bringing down the amount of disease. However, it doesn’t get patients into a good, deep remission to the point where we’re talking about stopping treatment for them. With ibrutinib, for example, patients go on this treatment and stay on treatment until either they come off for toxicity or it doesn’t work any longer, in which case they need to switch treatments because the disease is progressing. Usually, it’s many years that they’re on this treatment and that the disease would then progress. It’s a decision and a discussion with patients as to which strategy they prefer, with each having advantages or disadvantages. Similar to the patients who are young and have an unmutatedVgene, my preference is to manage the older population with the small molecule inhibitors because we get very, very good disease control and it saves them exposure to chemotherapy or chemoimmunotherapy and leaves other options open later.

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