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The data in the uMRD cohort of this trial suggest that fixed-duration therapy is feasible in patients who achieve undetectable MRD (uMRD) status. The selection of durations for these clinical trials can be arbitrary. Investigators hope that the follow up of patients who did not achieve uMRD within the initial fifteen months may show that longer “MRD-guided” courses of treatment can result in a better understanding of what is the optimal treatment duration with combination therapy of ibrutinib plus venetoclax. Investigators hope to publish this data at future conferences.
There are several reasons to look for fixed-duration treatments. Providers like fixed durations because they limit exposure to drugs which can impact side effects or toxicities. Further, investigators theorize that if you are not on continuous treatment, you reduce the chance of resistance developing to a drug and increase the potential to re-treat using this same agent. (See article in Recent Articles Section of our website that features an article by Dr. Meghan Thompson on successful retreatment with venetoclax.)
The question remains as to the advisability of stopping all therapy upon attainment of uMRD. This study begins to answer this question with 1-year DFS data that indicates little difference in outcomes for those who continue on ibrutinib versus those who stopped treatment because they received placebo. I personally am affected by this research as I was able to attain uMRD seven months after adding venetoclax to the ibrutinib I had taken for more than three years. My specialist and I agreed that there is still not enough long-term data for a high risk patient such as me to cease some form of therapy. It will be interesting to see data after longer follow-up in this clinical trial.
This is exciting early data that hopefully bring us closer to determining the efficacy of fixed-duration treatments in attaining uMRD and hopefully be able to withhold treatment for a significant period of time without relapse. There are many studies of different combinations being conducted world-wide to attempt to find the best combination of drugs with the lowest side effect profiles. In the past, the only fixed-duration treatments were chemoimmunotherapy which can have long-term toxic effects on our bodies, and raise our risk of infection and secondary cancers above levels associated with the disease itself.
Acalabrutinib, venetoclax and obinutuzumab in relapsed CLL: Phase 2 CLL2-BAAG trial results from the German CLL Study Group
18 month Follow up results with Ibrutinib/Venetoclax clinical trial
