Ruxolitinib, lenalidomide and methylprednisolone for relapsed/refractory multiple myeloma

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Published: 25 Sep 2019
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Dr James Berenson - Oncotherapeutics, West Hollywood, USA

Dr James Berenson talks to ecancer at the International Myeloma Workshop 2019 about using a novel combination of ruxolitinib and lenalidomide with methylprednisolone for multiple myeloma.

Dr Berenson explains why the results might be so good, alongside the benefits of it having low toxicity, and being a pill.

He outlines some molecular mechanisms which make this combination work, and explains the future exploration of this exciting new regimen.

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.

We have explored a very novel combination of using a JAK inhibitor called ruxolitinib, which is a pill, in combination with lenalidomide and steroids, not as Decadron or dexamethasone but as methylprednisolone. This three drug combination has been explored in a phase I dose escalation trial and then moved on to expansion. We’ve had very good responses in patients that are totally refractory to lenalidomide and steroids. In fact, half the patients have responded to this combination. The really good news is, number one, it’s a pill and, number two, it not only is well tolerated, people actually feel better. So it does mitigate some of the effects that you can see from lenalidomide in terms of fatigue, asthenia, effects on mental function with the addition of ruxolitinib and we see these patients really feel much better.

Again they respond and again it overcomes resistance to lenalidomide, it’s very exciting. We have a lot of preclinical data now that we generated to tell us why. It shuts down certain factors that drive lenalidomide resistance, it also beefs up the immune system in multiple different ways that were really not known, including getting rid of certain white cells called M2 macrophages that drive tumour growth and also reducing immune suppressor molecules that are on the surface of cells in the bone marrow that stop your immune system from functioning called PD-L1 and PD-L2.

So we are now exploring both single agent ruxolitinib with methylprednisolone but also we’ll be exploring this in a much larger way in bigger trials soon to come. So we’re very encouraged, we hope that this ruxolitinib will be explored in many other ways to treat myeloma and perhaps other cancers. This drug has really only been approved in the settings recently of graft versus host disease and initially in what we call myeloproliferative diseases – myelofibrosis and polycythemia rubra vera. But it looks like it’s going to be a player in cancer treatment and we’re excited.