Transcript
Mitchell Smith. I'm the Associate Cancer Director for Clinical Investigations at the George Washington Cancer Center in Washington DC.
My presentation is on the ECOG 1411 trial, which is a trial of first-line therapy for patients with mantle cell lymphoma. It's actually a 4-arm trial of bendamustine/rituximab-based therapy followed by rituximab maintenance.
In one of the arms, we add bortezomib to induction and one we add lenalidomide to the maintenance, and one arm gets both additions.
That study is fully-accrued for a couple of years and all patients have completed therapy, but the actual data for the trial, the readout for results is still pending. The presentation today is actually about minimal residual disease evaluation on this trial, which was built in as a laboratory correlative.
We compared 2 methods of assessing minimal disease. One is a standard flow cytometry that was done at the Mayo Clinic laboratories, and the other by Adaptive Biotechnologies' high-throughput sequencing, or NGS method.
That is a similar research application of what some people know as clonoSEQ. It is a commercially-available assay outside of the study. It was not at the time the study was developed.
What we're talking about today is still blinded as to our treatment arm, so it's cumulative data. What we noted was that the flow cytometry has a sensitivity of about 1 in 104 cells, so about 0.01%. And the NGS can be more sensitive than that, but in this case, we used that same cut-off.
Not surprisingly, when we look at those, they are fairly concordant. There's a few outliers, but in more than 90% cases, the 2 methods are concordant.
What we found was that by cycle 3 of induction, somewhat surprisingly, the vast majority, over 90% of patients are actually MRD-negative even after 3 cycles, and then by 6 cycles, again, a few people do convert.
Then there's one additional time point at 4 months into consolidation that was just done with blood by the NGS method, but the results were so good and the negativity rate by the end of cycle 6 that we didn't get additional information yet for that.
It was a bit surprising actually that the MRD rate was so high. We expected to have a lot of analysis about MRD-negative and positivity and conversion. That's encouraging for patients, and it tells us that bendamustine/rituximab is probably a good basis for future trials and that's been taken forward in a number of trials at this point.
Because so many people were MRD-negative, we did show the MRD-negative versus -positive, and it's not surprising that the people who had persistent disease at the end of cycle 3 or end of induction did not do as well as the others. But remember, about 90% of patients are MRD-negative.
The curves that we see are probably a broad approximation irrespective of treatment arm, and it says that the progression-free survival is probably on the order of 5 years or more with this treatment, which is fairly impressive for upfront mantle cell lymphoma.
Going forward, we will have additional analyses. We can quantitate the NGS data a little bit more and see if we go down to 105 or 106 sensitivity, if we can then delineate patients who have deeper responses and may do better.
One could think about doing targeted therapy. Certainly, we want to follow these negative patients to see if they convert to positive, can we intervene early. This data will evolve over time. And of course, we are very interested in knowing the differences among the treatment arms, which we will see hopefully in the next year or 2 at the outside.
The MRD assay is actually being used in 2 current ECOG trials to guide therapy, and so, it is going to be used to decide whether a patient might require transplant or more intensive therapy. Those studies are ongoing in the cooperative groups.
