“And I think the main message to be optimistic for patients about is, most of us in the academic world and doing research in this area are focused on fixed-duration treatment because we think that curative treatment will come with optimizing fixed-duration treatment, getting as many patients as we can, and as deeper remission as we can, and there will be patients cured potentially with that strategy.”
Having recently finished a firstline, Phase 2, FD (Fixed Duration) trial at M.D. Anderson with excellent results, the buzz that I hear there is that they wish they didn't have to use Obinutuzumab to achieve the deepest remission because it suppresses immunity for a long time after the last infusion. But they like the fact that FD less than about 18-24 months doesn't produce drug resistant clones. So the same treatment or a variation can be used again. This extends future choices.
The trials currently in progress were designed 3 years ago or more. The very latest drugs need to go through Phase 1 safety and dosage testing, and are usually tried in Relapsed/Refractory first because the risk is worth more for that group.
With this strategy combined with deep MRD testing (ClonoSEQ), the assumption is that the combination with the higher percentage of patients reaching U-MRDx by a given time is better. While my trial continued treatment for the few patients that did not reach U-MRD5, they tested to U-MRD6. The time variable is also something to experiment with to answer the questions:
"Does longer therapy to achieve U-MRDx produce a remission that lasts just as long?"
"Do patients who achieve U-MRDx and stop by an eariler Cycle still have the same length of remission?"
Currently FD is usually around 13 cycles - 1 year - of total treatment. There are cost savings for each cycle shorter. But data analysis for shorter trials becomes harder, and patients may wish they had longer therapy - hence the MRD driven (continue treatment if not U-MRD) strategy.
Finally, since my trial is Phase 2, it's not as large and diverse of a cohort as a Phase 3 trial. More patients are excluded in Phase 2 if they have cardio risk, or lower RBC, platelets, or neutrophils, for example. We do have a good variety of high risk FiSH and IHGV unmutated, though.
Ultimately, what I wish we had for my fellow patients was an analysis of risk markers of all types and the range of remission duration and adverse effects experienced that large Phase 3 trials can provide. That's hard to find even with existing Phase 3 results, even though I'm sure the data is there. With all the triplets (BTKi/CD20/BCL2) and doublets (BTKi/BCL2) being trialled, there's a possibility that more of us with risk combinations will have more choices of optimum treatment than now, where only TP53 and cardio risk matters.
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