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ASH 2020: Dr. Ian Flinn on Outpatient Debulking Prior to Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)

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Venetoclax is a potent treatment for chronic lymphocytic leukemia (CLL), but its use comes with the risk of tumor lysis syndrome. Tumor lysis syndrome or TLS is when a large number of leukemia cells die at once. You might think this would be a good thing, but it can cause the release of substantial amounts of uric acid and electrolytes, which is very dangerous for the patient because it can cause problems for the heart, kidneys, and nervous system.  

To lower the risk, venetoclax is slowly ramped up over five weeks starting with very low doses and checking labs frequently to ensure blood levels of uric acid, potassium and other electrolytes are within normal range.  

This slow ramp up has proven very successful with only 2% of patients developing TLS. Still isome patients who are starting treatment with a high tumor burden (very high lymphocyte count and/or massively swollen lymph nodes, venetoclax may need to be initiated in the hospital setting because of the risk of tumor lysis syndrome.  

Researchers have been exploring safer ways to initiate venetoclax treatment so that it can be used in an outpatient setting and expand accessibility. 

At the annual meeting of the American Society of Hematology (ASH) 2020Steven Bloom, CLL Society’s Chairman of the Board and President, interviewed Dr. Ian Flinn, director of lymphoma research at Sarah Cannon Cancer Institute in Nashville, TN. They discussed outpatient debulking prior to initiating venetoclax treatment for patients with CLL. 

Takeaways: 

  • Debulking is treating patients with a therapeutic agent prior to venetoclax treatment in order to kill off the leukemia cells in a more orderly and gradual way. The goal is to shrink the lymph nodes and bring down the lymphocyte count some prior to initiating venetoclax to minimize risk of tumor lysis syndrome, to reduce the bulk of the disease. 
  • Debulking offers a potential way to allow for initiation of venetoclax in an outpatient setting. 
  • In this study, researchers used obinutuzumab with or without bendamustine for debulking, and then were able to safely administer venetoclax in an outpatient setting. 
  • Use of bendamustine was encouraged if a patient had very large lymph nodes (10+ cm in diameter). 
  • About 75% of patients received obinutuzumab alone, and ~25% received combination obinutuzumab + bendamustine in an outpatient setting.  
  • Patients received cycles of obinutuzumab with or without bendamustine and were then evaluated for TLS risk. If patients met the criteria for moving from intermediate/high risk to low risk, then they could start on venetoclax. If they didn’t meet criteria, then they received more cycles (with a maximum of 6 cycles) of treatment. 
  • When low tumor burden was achieved, venetoclax was administered (5-week ramp-up schedule) as combination therapy with obinutuzumab for 5 months, and then as venetoclax monotherapy for a total of 1 year. 
  • Though the study is still ongoing, thus far 62% of patients have achieved complete remission. 

Conclusions: 

This research is still ongoing, but it appears to provide a safe way to administer the venetoclax + obinutuzumab treatment regimen in an outpatient setting. The ability to administer venetoclax safely in outpatient settings could expand accessibility as community practices would be able to offer venetoclax treatment, and this would also greatly reduce the burden for patients. 

Please enjoy this interview with Dr. Flinn from the virtual ASH meeting, which was held December 2020.

You can read the actual ASH abstract here: Debulking Regimens Prior to Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Interim Results from a Phase 3b Study 

Take care of yourself first.  

Ann Liu, PhD 

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