Combination chemotherapy for multiple myeloma

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Published: 11 Dec 2017
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Dr Muzaffar Qazilbash - MD Anderson Cancer Center, Houston, USA

Dr Qazilbash speaks with ecancer at the ASH 2017 annual meeting about the outcomes of a phase III trial of melphalan with busulfan as induction therapy for multiple myeloma patients.

He outlines the current schedule of induction therapy, and improvements in response duration and progression-free survival seen in the experimental arm.

Dr Qazilbash also describes the increased toxicity as reversible, and with no particularly vulnerable patient group, recommending the combination for further evaluation in larger trials.

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

 

For multiple myeloma stem cell transplantation using patients’ own cells is one of the standard therapies. When we do stem cell transplantation, before we give stem cells we wipe out patients’ disease with high dose chemotherapy and the drug that is used most commonly for that is melphalan. This has been in use for several decades now and people have tried to improve upon that but so far no other regimen has been found to be superior. So there is some data that this combination of busulfan and melphalan may do better than melphalan, so with that background we designed a phase III trial to compare melphalan with busulfan plus melphalan as a regimen for stem cell transplant for newly diagnosed myeloma patients.

When it came to the patient cohort for the people involved in this trial could you tell us more about that?

All the patients had multiple myeloma and they had to be eligible for stem cell transplant. Generally they were up to age 70, which is what most of the transplant eligible patients are, and they had received what is called induction treatment – a few cycles of combination therapy before coming to transplant. There were 204 patients who were enrolled in this trial, 104 in the busulfan arm and 100 in the melphalan only arm. As one would expect in a trial like this, these patients were fairly well matched in terms of age and ethnicity and the type of disease that they had.

When it came to results what did you find?

What we found was that this combination drug, because it was a more intense regimen, was associated with more side effects. So these patients had more mouth sores and they had an increase in their liver function tests and they also had more neutropenic fever, some of them requiring hospitalisation. But all these side effects were reversible and patients fully recovered. There were no deaths related to either the two drug or the single drug regimen and in terms of response to treatment at 100 days or at last follow-up the response was pretty much the same. What was most interesting and encouraging was that the patients who were treated in the two drug arm had a longer time to progression; they stayed in remission longer and as a result the progression free survival was significantly longer in the two drug arm versus melphalan only. That was particularly noticeable for patients who are considered to have high risk multiple myeloma that traditionally do worse than the standard risk patients. So this was the key finding, that although we saw more side effects with the two drug regimen those were reversible and, most importantly, we saw a longer progression free survival with the two drug regimen.

Do you see the significance as being worth the cost in toxicity and drug availability then?

At this point since the toxicity was reversible and progression free survival is still, especially in the high risk patients, pretty dramatic, our assessment is that, yes, it is worth exploring further, perhaps in a large multicentre trial in a bigger and more diverse patient population. If these results are validated and confirmed this may become the new standard for chemotherapy for stem cell transplant for multiple myeloma.

You mentioned that the patients were fairly well matched, were there any particular indicators for, for example, age or fragility for people who would be less suited to the combination?

For the age group that we used this for we did not see any signal for increased toxicity. All the patients who were eligible for the study did equally well.