Complete remission after induction chemotherapy determines clinical efficacy of relapse-preventive immunotherapy in AML

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Published: 17 Dec 2019
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Prof Kristoffer Hellstrand - University of Gothenburg, Gothenburg, Sweden

Prof Kristoffer Hellstrand speaks to ecancer at the 2019 ASH meeting in Orlando about the impact of previous induction chemotherapy in patients with acute myeloid leukaemia (AML).

He explains that this study investigated the effect of immunotherapy in the post-chemotherapy phase, which aims to target residual disease which is the most common cause of relapse and death in these patients.

Prof Hellstrand describes the design of this trial which found that if patients achieved complete remission after one cycle of induction chemotherapy, immunotherapy was efficacious in this population.

He also states that these findings were more pronounced in younger patients, compared to the older population.

This program is funded in part via an independent grant from AbbVie. ecancer is editorially independent and there is no influence over content

 

Complete remission after induction chemotherapy determines clinical efficacy of relapse-preventive immunotherapy in AML

Prof Kristoffer Hellstrand - University of Gothenburg, Gothenburg, Sweden

It’s about acute myeloid leukaemia and, as you know, patients with acute myeloid leukaemia undergo in the beginning, in the first phase of the disease, several courses of chemotherapy. What we have done is to develop an immunotherapy after the completion of chemotherapy to prevent relapse of AML in the post-chemotherapy phase. Relapse is a major cause of death in this disease, especially in younger patients. I assume that relapse is the major cause of death. Still there are few efficacious methods to avoid a relapse. Once patients have completed chemo they are normally free of leukaemia from a microscopic point of view but there is sometimes residual leukaemia and immunotherapy thereafter aims at just reducing or eradicating those residual leukemic cells. That’s what we do.

In this abstract we just show that patients where the initial chemotherapy has been efficacious they are much more likely to respond favourably to the immunotherapy with, as in this case, Ceplene and IL-2 in combination, Ceplene/IL-2.
We did a phase III trial that was published some years ago and what we did for this particular work was to define which patients responded and which patients didn’t. We identified this particular aspect of induction chemotherapy that if patients achieved complete remission after one induction then the immunotherapy was much more efficacious.

The primary endpoint, or the endpoints, of the trial are, as in many such trials, relapse risk and overall survival. What we did was to monitor that sequentially over time and noted that the rate of relapse was much lower in patients receiving Ceplene/IL-2 provided that the initial chemo had been efficacious.

One conclusion is that this trial identifies patients who are likely to respond to Ceplene/IL-2 therapy for remission maintenance but it also defines patients who should go on to other therapies, maybe experimental therapies and such.

For the design of future therapies, future immunotherapy, for AML, similar therapies, then this particular group of patients where the initial chemotherapy has been efficacious is a much better study group to define efficacy.

Older patients overall responded relatively poorly to Ceplene/IL-2 whereas the effect was very pronounced in patients below 60 years old.

We need to redo this study in this particular population and define further which patients are suitable for treatment and, again, who should go onto other therapies.