Thrombosis risk and management in multiple myeloma

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Published: 2 May 2018
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Dr Joseph Mikhael - Chief Medical Officer of the International Myeloma Foundation

Dr Mikhael speaks with ecancer at the 2018 Myeloma Knowledge Exchange about thrombosis in multiple myeloma, in particular it's incidence and treatment.

He emphasises looking at the history and risk factors of a patient, which includes close patient communication.

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

We know thrombosis occurs in all cancers; usually we think of it as mitigated by three factors: patient factors, disease factors and treatment factors. These are particularly important in multiple myeloma – patient factors by virtue of the fact that myeloma patients tend to be older and we know that thrombosis is more common. Disease factors because multiple myeloma is a disease that not only generally has an increased incidence of thrombosis but we know, because of the cytokine release, because of the bone marrow microenvironment, that early on myeloma has a high risk of thrombosis and about 50% of clots occur in the first 4-6 months of a patient’s treatment. But we know the remaining 50% can be throughout the rest of their lives so there is a continuous risk. Then lastly, and perhaps most importantly in myeloma, treatment related factors. Because we use a lot of agents like steroids, like combination chemotherapy and in particular immunomodulatory drugs, we see a significant risk of thrombosis in multiple myeloma.

In our session today we reviewed the incidence and the causes of thrombosis in myeloma patients, as discussed, patient factors, disease factors and treatment-related factors. Then we reviewed the latest evidence for treating patients, both for prevention and prophylaxis of developing a clot and to treat those who unfortunately do develop a clot. The overall theme of our discussion today was to be aware of the importance of risk stratification in myeloma, that is to say noting that if patients have certain risk factors they need more than prophylaxis with aspirin when patients are being treated with immunomodulatory drugs, that we’re typically using a low molecular weight heparin. But that also as we are seeing changes in the thrombosis world they are now beginning to affect the myeloma patient. This is perhaps the most important new learning point – that we have greater and greater evidence now for the use of anti-Xa agents in thrombosis. Historically a lot of those patients were excluded from trials if they had had cancer but now we have cancer-related anti-Xa trials that are demonstrating at least non-inferiority to low molecular weight heparins. I presented the most recent study that was presented at ASH where there was a comparison of a low molecular weight heparin versus an anti-Xa agent in established cancer patients who had thrombosis, showing that the risk of recurrence of thrombosis was lower in those patients who received the anti-Xa agent although slightly offset by a slight increased risk of bleeding. So although it doesn’t have this formal indication yet, I think we can see a future in myeloma where for both prevention and, indeed, for treatment of thrombosis we’ll be using anti-Xa agents.

Do we know how long it might take until these treatments are used on a regular basis?

It’s starting to happen already, of course, as these drugs are approved for indications of thrombosis. In particular in the United States we’re starting to see it used more and more – it’s easier for patients, there’s less obviously intervention than with subcutaneous injection. The maturing of these trials to publication and formal approval will likely happen over the next two years but even within those two years we will see a greater use of Xa agents and dramatically less use of vitamin K antagonists which is already happening in the cancer world.

Is there anything that patients can do to lower their risk of thrombosis?

We know that a lot of the risk factors we can’t even measure or fully understand but there are some things that can be behaviour related of which perhaps the most important is obesity. We know that that’s not simply managed either but we do know that with increasing obesity and certain levels of body mass index that can increase a risk of thrombosis. So that’s an important factor. Then, of course, adherence to the medication regimen that patients are on is secondly very important. Then the third piece of advice I would share with my patients that I share with them regularly is to be aware of the signs and symptoms of thrombosis which would namely be pain or swelling of one of the legs more than the other or a shortness of breath that is not easily resolved. Those kinds of signs and symptoms can help us detect a clot sooner so we can intervene more quickly.

Generally speaking, when a patient does develop a thrombosis the chemotherapy or the treatment regimen that they’re on may be suspended for a short period of time as we introduce an anticoagulant and that may be in the form of a low molecular weight heparin, potentially an anti-Xa agent, as I’ve mentioned. Usually within the first week or two we already start to see a change as we stabilise the clot, as it were, and then we can usually reintroduce their treatment. Because we don’t want the treatment of their cancer to suffer, their myeloma to suffer, by virtue of the thrombosis.
In some extreme cases with very worrisome thromboses there may have to be a hospitalisation, there may have to be other interventions but for most people it’s starting a new therapy either with a low molecular weight heparin or with an oral regimen.

Any final thoughts?

One of the take-home points that’s so critical for us, for practising clinicians, is the importance of taking a very careful history. One of the most important risk factors for a patient is that they have either a personal or a family history that is significant of thrombosis. That’s a lot better than ordering any test or taking bloodwork. That communication with the patient is so important in all of supportive care but in particular in thrombosis.