ESH 2014: Prof. Hallek Discusses Clinical Trial Goals in CLL

In Part 2 of our interview from ESH (European School of Hematology) 2014, Professor Michael Hallek who heads up the German CLL Study Group  goes deeper into the details of his clinical trial goals. If you haven’t already watched part 1, it will help with your understanding of our continued conversation if you watch it first. Click here.

Take Away Points:

• Trials are being developed in Germany to limit the duration of therapy and at the same time increase efficacy.
• Using MRD- (minimal residual disease negative) is a critical marker in determining the need for more therapy.
• Future therapy may be guided the presence or absence of minimal residual disease (MRD).
• FCR when used for treatment-naïve patients with specific prognostic factors, (mutated with trisomy 12, deletion 13q and deletion 11q) produces extremely durable remissions (>10 years) that are suggestive of a cure.

PREFACE:

Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting. With time and experience, you’ll become familiar with the terminology and acronyms. We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We will also provide a glossary of terms and acronyms for your reference.

Professor Hallek on Clinical Trial Goals

Similar to Professor Hillmen (click here for the first part of our three part interview) who heads up the equivalent British research consortium, Prof. Hallek plans a “fast boat” adaptive strategy with small agile trials. He is looking to be very selective, and as a result cost-effective, in determining which of us would benefit from maintenance therapy, and in whom a quick therapeutic intervention might consolidate our response and when it might be unnecessary. The Goldilocks’ solution: Enough but not too much therapy for our cancer.

The Optimum Role of FCR

In the last few minutes of our conversation, Professor Hallek argues, with strong evidence to back him up, about the very durable and deep results with FCR (fludarabine, cyclophosphamide, and rituximab) in a select group of patients.

He rightly cautions us to be thoughtful before discarding such a good therapy. For more discussion on this topic, please check out my personal take in this monologue on chemotherapy found here.

I would point out that while he describes the great results achieved with those patients that have the bad luck to have deletion 11q, it is extremely rare to find one of us patients whose cytogenetics shows a missing piece of the long arm of the 11^th chromosome (deletion 11q) who also has the good fortune to have the more indolent (slow growing) form of CLL where the IVGH gene is mutated. Sadly most of us with deletion 11q, are also unmutated, myself included. And while our FISH status may evolve over time (see Dr. Wu on clonal evolution here), our mutation status never changes. That said, there is clear evidence that any patient with deletion 11q does better with FCR compared to F alone or even FR.

Summary:

Professor Hallek in Germany and Professor Hillmen in the UK are not only asking the right questions, they are asking them in ways that we can get quick answers. We are rapidly moving towards smart long-term control of our disease. Let’s hope it is fast enough for all of us in need.

Please enjoy listening to Professor Hallek’s thoughtful and deliberate approach to helping us.

Brian Koffman 6/25/15