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At the international meeting of ERIC (European Research Initiative on CLL), 2018 in Barcelona, Dr. Koffman interviewed Dr. Stilgenbauer on the promise of sequential and combination therapies in CLL.
Below are some points from their interview, in which Dr. Stilgenbauer describes chronic lymphocytic leukemia sequential treatment from a patient’s point of view.
- The problem: Historically, we’ve had chemo-immunotherapy for CLL. New BTK and BCL-2 inhibitors were approved, but as monotherapies (one drug at a time) and for long treatment durations, raising the risk of resistance. That suggests two options, that many investigators are studying now:
- Could we get better results if we sequence these different treatments?
- Or should we combine several drugs into a single treatment?
- Sequential Therapy
- Can we find particular sequences of drugs, dosages and durations that we could give once, and get long survival?
- In CLL, resistance occurs when a newly mutated clone arises.
- Maybe following one drug with another will wipe out the clone resistant to the first.
- Then we may find that the first drug is still effective. (see note 2).
- If a patient relapses on sequential treatment, we know venetoclax can help patients recover. We already have good data on that, and we see good outcomes.
- Combination Therapy
- The goal is to find a combination of drugs given at once for a short duration, that will give long and deep remission. (See note 3).
- Hopefully if a patient relapses, by the end of remission any resistant clones will have died out, and the same combination will be just as effective.
- A concern: if a patient relapses after a combination therapy of 2-3 drugs, and resistant clones don’t disappear, doctors don’t have any data on where to go next.
- Final thoughts from Dr. Stilgenbauer
- The treatment options make this a complicated, but a very hopeful time.
- What a patient can do:
- stay informed about treatment options. This includes types of therapy: Mono, Sequential, Combination – where before there was only monotherapy to talk about.
- With your doctor, plan to make your own treatment decisions between a wide range of choices.
- Participate in clinical trials if you can.
Here is Dr. Koffman’s interview with Dr. Stephan Stilgenbauer on the lecture that he gave ERIC, 2018 in Barcelona.
Note 2: See, for example, the study from Ohio State: “Venetoclax for Chronic Lymphocytic Leukaemia Progressing after Ibrutinib: a Multicentre, Open-Label Phase 2 Trial. “(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027999)
Note 3: MURANO trial: Venetoclax + Rituximab vs. Bendamustine + Rituximab
See, for example, a report of the MURANO phase III clinical trial, “Venetoclax–Rituximab in
Relapsed or Refractory Chronic Lymphocytic Leukemia” Seymour et al, 2018 (NEJM)
Full text online, at https://www.nejm.org/doi/full/10.1056/NEJMoa1713976