ASH 2018: Dr. Pete Hillmen on the CLARITY trial of the combination of ibrutinib and venetoclax in relapsed or refractory CLL (chronic lymphocytic leukemia)

Dr. Peter Hillmen out of Leeds has developed innovative research techniques to quickly advance the treatment options for CLL patients in the UK.

His Trial Acceleration Program (TAP) have changed how CLL research is being done. To better understand the importance of this change, please see this interview here from back in 2014 and follow through to Part 2 and 3.

This CLARITY trial of 50 ‘tough to treat’ relapsed and refractory chronic lymphocytic leukemia patients is part of that TAP program that combines two of arguably the best new drugs to treat CLL: ibrutinib and venetoclax.

Take Aways:

• There were no new safety signals with the combinations of ibrutinib and venetoclax, just the expected side effects. In other word it is a safe combination.
• Only 1 of the 50 CLL patients had biochemical tumor lysis syndrome (TLS) that was not clinically significant and easy to manage. TLS, a potentially life-threatening complication when too many cancers cells are killed too quickly that overwhelms the body’s ability to deal with all the chemical debris, is now largely controlled with the new dosing protocols for venetoclax.
• The combo is very effective.
  • 39% U-MRD (undetectable measurable disease or < 1 in 10,000 lymphocytes is a CLL cell) was achieved in the bone marrow at 1 year with more responding later.
  • 94% responded and >1/2 had a complete remission (CR).
  • Only 1 patient had progressive disease.
• U-MRD might be a more important marker than a complete remission for projecting how well we will do long term with our CLL/SLL.

Conclusion:

There are two big points that I want to emphasize.

First, the future for CLL treatment is more clearly coming into focus and it is looking as if is going to be fixed duration cocktails of targeted agents.

In fact, to quote from the abstract:

“The Bloodwise TAP CLARITY trial combined ibrutinib with venetoclax in order to eradicate detectable CLL with the intention of stopping therapy”.

The success of this trial has led to doing a similar trial for frontline therapy.

Second, is the increasing recognition that U-MRD may be a better prognostic marker that a complete remission (CR). To be diagnosed with a CR, among other things, all nodes need to have shrunk back down to a normal maximum diameter of 1.5 cm. Sometimes enlarged nodes may get somewhat smaller, but never return to normal size due to scar tissue, but not due to persistent CLL. It is worth listening to Professor Hillmen expound on this.

The real takeaway is that the future looks bright for us patients with chronic lymphocytic leukemia, and we owe huge thanks to researchers such as Dr. Hillmen and to all the brave patients that enroll in these trials.

Here is my interview with Prof Hillmen from the last day of ASH 2018:

Here is the actual abstract that Dr. Hillmen updated when we talked:

http://www.bloodjournal.org/content/132/Suppl_1/182

Stay strong

Brian