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EHA 2019: Dr. Susan O’Brien on Frontline Therapy in CLL

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Dr. Susan O’Brien moved from MD Anderson to head up the CLL research and clinical team at the University of California at Irvine (UCI), and we chronic lymphocytic patients in southern California are happy to have her.

She is a powerful advocate on our behalf and a smart clinician who carefully considers the best options for the patient in front of her.

In this interview from EHA (European Hematology Association) Annual Congress held in Amsterdam in 2019, she shared her strong opinion on how CLL should be managed frontline.


  • FCR may still have a role in young healthy patients with mutated IGVH and no other poor prognostic factor, but it is only for a very small select group of CLL patients. For those patients, more than half may be cured of their CLL with only 6 months of therapy.
  • O’Brien sees no role for Bendamustine and Rituximab (BR) in treating CLL. There is no data to suggest some patients are cured.
  • For most patients, a novel agent is the best choice.
  • The decision comes down to a choice between the two approved frontline options using novel agents, namely ibrutinib and much more recently venetoclax plus obinutuzumab (V+O).
  • 5-year survival on single agent ibrutinib has > 80% survival based on the data from the Resonate 2 trial.
  • There is no similar long-term robust data for V+O, but it is appealing for a number of reasons:
    • Treatment is fixed duration lowering cost and even more importantly, perhaps lowering the risk of developing resistance.
    • Many patients are reaching levels were their CLL is undetectable (U-MRD or undetectable minimal residual disease). This rarely happens with single agent ibrutinib.
    • There are some patients now several years out on venetoclax who continue to do well.
  • There is less data for 17p del frontline as only 5-7% have 17p del before chemotherapy but it seems response rates are nearly as robust for both treatment options as they are for those without it, so the presence of 17p deletion or TP53 doesn’t really help guide therapy.
  • Clinical trials are always a good option when appropriate.


What is clear from this interview is that for nearly all patients, chemo should be off the table and that for each and every patient, BR should not be an option. There is proof that we have better therapies!

Yet too many patients are still getting FCR and BR. That is why we at the CLL Society are here. To educate patients about their best possible care. To help patients get appropriate testing before treatment and when necessary a second opinion.

With any therapy what is ultimately most important to patients is how long will the remission last, not just the response rate. We have better long term ibrutinib data today but that may be only because the V+O option is so new. That is why research is so important.  Appropriate sequencing and combinations are where that research is going in CLL.

As Dr. O’Brien stated, we have an embarrassment of riches to treat our chronic lymphocytic leukemia.

Please enjoy my interview with Dr. O’Brien.

Thanks for reading and listening.

Stay strong. We are all in this together.

Brian Koffman