I recently responded to this question posted on CLLSLLyahoogroups forum by C. M.
".... If these new drugs [kinase inhibitors] are so effective it makes sense not to "wait" for our white counts to rise and all the other side effects of the CLL. Are there any trials using Ibruitinib on CLL patients who have not had treatment?"
My reply, here expanded a bit, as follows: While it is unknown that allowing the increase of B-cancer cells, particularly in the peripheral blood, does not cause harm it is not apparent that any potential harm from accumulation is greater than current TX (treatment) options taken early in disease diagnosis. The question of Early Front-line use for kinase inhibition drugs like Ibrutinib or Idelalisib is not a slam-dunk based solely on their extraordinary efficacy to date. The following questions need to be considered if not answered and for which we need more time to gather appropriate data.
1) Ibrutinib in use today permanently and irreversibly blocks both BTK (Bruton's Tyrosine Kinase) and ITK (Interleukin 2 Inducible T-cell Kinase) for given cells on a daily basis. Keep in mind that these kinases are part of needed cell functioning activity under normal conditions so we do not know what stopping the pathology of cancer hijacked BTK and alteration of our T-cells by ITK inhibition does to beneficial kinase function as related to the overall function of the humoral or adaptive immune system.
2) Ibrutinib is not a cure and has produced very few CRs (Complete Remissions) as a monotherapy and if no longterm side effects arise, may have to be taken on a daily basis for the rest of a patient's life, so in patients who are in their 30s, 40s or 50s at a cost of ~$100,000.00 to $130,000.00 USD per year, do the math. Yes - Money matters, sad to say.
3) It is a different question as to being prescribed Ibrutinib when first diagnosed when a patient crosses the line from MBL(Monoclonal B-cell Lymphocytosis) to CLL, than giving Ibrutinib as a front-line therapy after a standard waiting period (W&W) when "B" symptoms appear, making TX necessary. Many years of high quality function can be the experience for many patients on W&W.
4) On the pro-early TX side of the argument, it is possible that early treatment might prevent clonal evolution leading to a more dangerous CLL from emerging but that is only speculation at this time. There should be some experimentation for this to be studied. What studies from about four and a half years of Ibrutinib use are telling us, is that frontline treated patients are doing better than chemo beat up patients even though both groups respond very well. In a time of rapid therapy development a strategy to argue for earlier Ibrutinib use could be made that by the time any potential bad side effect might show up a newer treatment - less toxic than chemo based options will be available. Gotta have faith for that one. In the oft chance that a longterm side effect could rear its head in the arena of humoral immune function, one could rationalize that any disfunction might easily be reversed by simply stopping the Ibrutinib therapy. This is unlike purine or alkylating agent damage that we know cannot be reversed once it shows up e.g. MDS (Myelodysplastic Syndrome) & secondary cancers likely to be more frequent with chemo.
5) On the anti-early TX side of the argument it is unknown whether permanent BTK/ITK blocking for prolonged years will inhibit the ability for a person to make novel antibodies to new biological threats that adults have not encountered in the past. If this speculation plays out I would imagine that younger patients would be more vulnerable to infections than older patients as a general rule. Even in the frontline treated monotherapy Ibrutinib patients there is not 100% PFS (Progression Free Survival) and relapses are occurring more frequently in chemo beat-up patients. The message applied to all treatment therapy is at this time to expect that the earlier one starts TX the sooner one may expect to relapse. Immune function under perpetual long term kinase inhibition may be analogous to turning an oil tanker around - It takes a long time but its direction can be reversed. Time and selective use of Ibrutinib will yield much need info as the years pass.
6) More Trials to include frontline use in previously untreated patients and other novel use combination Trials with Ibrutinib are coming up soon. This is difficult for those needing TX now but keep your eye on the website <www.Clinicaltrials.gov>
I am a lay-patient with no medical training and anything I write should be viewed in that context.
WWW - Ibrutinib monotherapy (280mg daily) lab-rat in the early Phase I R&R (Relapse & Refractory) Clinical Trial at OSU Medical Center under Dr. John Byrd - just past 30 months, PR (Partial Remission) still deepening as of last monitoring and feeling good with no apparent side effects to report.