Improved outcomes from quadruplet KCRD induction in newly diagnosed myeloma patients

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Published: 25 Sep 2019
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Dr Charlotte Pawlyn - Royal Marsden Hospital, London, UK

Dr Charlotte Pawlyn speaks to ecancer at the 2019 International Myeloma Workshop meeting in Boston about the transplant eligible pathway of the NCRI Myeloma XI Phase III trial.

Dr Paylwn explains that she was presenting results comparing quadruplet KCRD (carfilzomib, cyclophosphamide, lenalidomide and dexamethasone) and triplet combination induction therapy in newly diagnosed patients.

Dr Pawlyn reports that the quadruplet therapy induced higher rates of MRD negativity.

Additionally, patients who were MRD negative were found to have improved outcomes when compared with MRD negative patients who were treated with the triplet combination.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

I presented data from the Myeloma XI trial. This is a large national trial that we ran across the UK at over a hundred centres. We recruited more than 4,000 patients to the trial. The trial had pathways for transplant eligible and transplant ineligible patients. The data that I presented here was for patients in the transplant eligible pathway the results of the randomisation between the quadruplet using the second generation proteasome inhibitor carfilzomib combined with cyclophosphamide, lenalidomide and dexamethasone. It was looking at outcomes for those patients in comparison to the control arm in which patients received a triplet combination induction therapy with immunomodulatory drug based triplet therapies.

The results that I presented found that the patients who received the quadruplet combination had higher rates of very good partial response or better and also higher rates of MRD negativity. That was associated with an improvement in progression free survival for the patients who had this very active quadruplet combination as their induction therapy.
We found that the quadruplet induced higher rates of MRD negativity but also that those patients who were MRD negative if they had received the quadruplet combination had improved outcomes compared to those patients who had received only triplet therapy. We’re waiting for the overall survival data to mature from the study but we have some insight from the progression free survival 2 data. So this is the outcomes from randomisation to second disease progression, and this also identified a benefit for patients receiving the quadruplet combination over the triplet combinations.

How might these results impact clinical practice?

What we found was that improved outcomes were associated with this highly active induction quadruplet combination including the second generation proteasome inhibitor carfilzomib. One of the other interesting things we found was that when we looked at the achievement of MRD negative status we found that patients who became MRD negative at the end of induction therapy had improved outcomes compared to those who were MRD positive at that time point, even if the MRD positive patients had subsequently converted to be MRD negative after transplant. So this really, whilst reinforcing the need for transplant in the up front setting, also suggests that the induction regimen is still very important in achieving deep responses early. It’s associated with improved outcomes.