Practical Information for Venetoclax in CLL

Danielle Brander, MD:In addition to participation in the clinical trial of venetoclax and rituximab, since venetoclax has been approved, I’ve not used the regimen of venetoclax plus rituximab in several previously treated high-risk patients with deletion 17p. My reason for selection of the venetoclax, again, is based on what the patients had prior, and under the current approval, these are the very high-risk patients who have deletion of 17p.

The reason I add rituximab for these patients is that, again, based on some of the earlier studies and then an analysis of venetoclax/rituximab versus venetoclax alone, there at least seems to be an additive benefit in the response and duration of response to therapy when you’re adding in the rituximab. This is particularly true in my experience for patients who have had a long interval since they’ve had rituximab, or if patients, such as the patient in this case, actually have never had exposure to an anti-CD20 antibody. Anti-CD20 antibodies such as rituximab have historically been very key to the treatment of CLL and, therefore, I think it can benefit patients, again, if they have not had it for a period of time or if they’ve, in this case, never had the treatment.

As I highlighted before, the way that the rituximab is given with venetoclax needs to be after the patient reaches the full dose of venetoclax. Again, this is primarily out of a concern for safety in that you want to make sure patients are tolerating the venetoclax alone, both from a tumor lysis standpoint and a cytopenia standpoint, before you are adding in the rituximab.

Overall, however, once patients added this in, they generally do well. We’re looking for the results of some of the larger studies to know if this does seem to increase some of the other toxicities, such as neutropenia. However, I would highlight in studies thus far, the neutropenia being of higher incidence does not necessarily translate into higher risk of febrile neutropenia or higher risks of other adverse outcomes from their cytopenias. Most patients can be managed through this time period with no expectations of this to happen and can receive growth factor, other standard of care approaches.

The one last thing that I also always counsel patients about, as well as discuss with the other oncologists that I may be collaborating with in care for the patient, is that it’s always best to err or the side of safety. Again, the dosing guidelines are a nice guideline to help us assess whether a patient is low-, moderate-, or high-risk based on their tumor burden for either the start of therapy or the addition of any rituximab later. However, you know the patient best sitting in front of you, and if they’re a higher risk because of perhaps borderline kidney function or they’re coming directly from another prior therapy with a more rapidly progressing disease, then it’s better to be conservative and manage the patient more aggressively for tumor lysis so that the patient can both be safely treated as well as long-term benefit from the response of the treatment.

Transcript edited for clarity.

Case: An Older Patient with Relapsed CLL

March 2015

• A 70-year-old female reported symptoms of weight loss, fatigue, and pain in the upper left portion of her abdomen
• PE showed moderate axillary lymphadenopathy and splenomegaly, spleen palpated 7 cm below the costal margin
• Otherwise, the patient is overall well-appearing and continues to exercise
• Laboratory results:
  • WBC, 48,000; 73% lymphocytes
  • Hb, 10 g/dL (1 year ago Hb, 12 m/dL)
  • Platelets, 125,000/mm³(1 year ago platelets, 165,000/mm³)
  • ANC 1,800/mm³(WNL)
  • LDH, 250 U/L
  • Beta-2-microglobulin, 4.2 µg/L
• Cytogenetics by FISH showed 17p deletion in 56%
• IgVH unmutated
• Bone marrow biopsy; diffuse infiltration by CLL
• The patient was enrolled in a clinical trial and was treated with ibrutinib 420 mg daily
• After 18 months, she achieved complete remission of her disease and resolution of her symptoms

November 2017

• The patient developed had developed atrial fibrillation and despite cardiology interventions could not restart ibrutinib
• During routine follow up, the patient reported increasing fatigue
• PE: cervical lymphadenopathy, ~4 cm; spleen, palpable 8 cm below the costal margin
• Normal kidney function
• Laboratory results:
  • ALC; 112,000 cells/mL
  • Hb; 10.8 g/dL
  • Platelets; 105,000 cells/mm³
• The patient was started on venetoclax