Transcript:
Good morning. I'm Dr. Joseph Connors. I'm an emeritus clinical professor at the British Columbia Cancer Centre for Lymphoid Cancer where we've focused on Hodgkin lymphoma for many years.
Today I'm going to comment on my presentation about what is the best choice for the treatment of advanced-stage Hodgkin lymphoma in 2019. I've taken the approach of looking at three different strategies for approaching the disease.
The first of them is to see if we can use PET-driven or PET-directed treatment to reduce the toxicity of treatment and the examples I've given are focused on three different trials.
The first of them choosing to use ABVD and see if a PET scan done after two cycles, an interim or a PET2 scan, if negative, does this provide us with guidance to allow us to reduce the intensity of treatment?
The response-associated treatment of Hodgkin lymphoma trial -- the RATHL trial -- demonstrated that if the PET scan after two cycles is negative, one can drop bleomycin from further treatment. The net effect for the whole population of all the patients treated is about a 50 to 55 percent reduction in exposure to bleomycin, a desirable goal.
The other two trials focused on the use of escalated BEACOPP as the primary treatment. The first of them choosing in the experimental arm to reduce the exposure to treatment by shortening the total course of the escalated BEACOPP to four cycles, or two cycles beyond the negative PET2 scan, or continuing if the PET scan was positive.
The second of the trials chose to examine a similar PET-driven approach with the PET-negative patients reducing their treatment from BEACOPP down to ABVD, and only continuing with full dose escalated BEACOPP if the PET scan, after two cycles, was positive.
Both demonstrated that one can safely reduce the intensity of treatment for the patients with negative PET scans.
The second of the two showed that the PET-driven approach allows about a 55 percent reduction in the overall exposure of the population to the escalated BEACOPP, a desirable goal.
However, a cautionary note, they had to change the definition of PET2 negativity and escalated the intensity all the way up to include Deauville scores 1, 2, 3, or even 4. If there was less than 40 percent of an SUV, compared to the liver in the positive lesions, meaning that we have then a new definition that would require a validation.
I think it is fair to say, though, that if you start with ABVD, you can reduce toxicity using an interim PET. If you start with escalated BEACOPP, you can reduce toxicity, but in neither approach are you actually improving the outcome for the overall population. We haven't increased effectiveness.
Can we do that using a PET-driven approach? Two trials examined that. The RATHL trial that I already mentioned and the SWOG trial in which the patients with PET2 positivity had an escalation from ABVD up to escalated BEACOPP.
In both cases, a probable improvement in outcome for the patients who are PET2 positive seem to result with an improvement in the progression-free survival up to about 65 to 70 percent, an apparent gain. I say it that way because it wasn't a randomized comparison. That's a comparison back against historical controls.
The answer is yes. One might improve effectiveness if adopting a PET-driven analysis and choosing to escalate from ABVD to intensified therapy in the PET2 positive patients. This will only profit about 15 percent of the population and, even so, still about a third of those patients, even with the escalation, will eventually relapse.
Finally, can we make things turn out better? Can we improve effectiveness or efficacy by adding an additional agent?
That was examined in the ECHELON-1 trial which compared, from the beginning, patients with advanced-stage Hodgkin lymphoma receiving ABVD standard treatment with AVD+brentuximab vedotin, the experimental arm.
If we jump right to the bottom line, it's clear that the experimental arm eliminated about 30 percent of the likely relapses that otherwise occurred if patients stuck with the traditional regimen of ABVD.
Changing the likelihood of a possible cure of the disease by that amount and indicating that one might be able to improve efficacy with the addition of an additional agent.
Interestingly, since no PET-driven decisions were made in that trial, we can look at the patients who were PET2 positive. The ones that, of course, would have received intensified therapy in the earlier trials that I described. We can look to see what became of them on this trial.
On the experimental arm, interestingly enough, the patient population that was PET2 positive had just shy of a 70 percent likelihood of remaining disease-free, apparently achieving the same likelihood of reducing the likelihood of failure in the PET2 positive patients with the simple addition of an additional agent.
To return to the original question, where do we stand in 2019?
Yes, we can reduce toxicity primarily if one is interested in cutting toxicity while sustaining the same response rate. We can improve efficacy with an escalation-derived treatment if we have started with ABVD, but only in a very small minority of patients and only modestly.
Alternatively and finally, we can improve outcome modestly but clinically significantly with the addition of an experimental agent, brentuximab vedotin, and at the same time, have the ancillary benefit of reducing the toxicity by eliminating the bleomycin.
I think we've continued to make progress in the treatment of Hodgkin lymphoma. Fortunately, our patients and our clinicians have a variety of choices that they can choose across, but we have thought of ways to make outcomes better for patients with advanced-stage Hodgkin lymphoma now in 2019.
Thanks for joining me.
