Transitioning from bortezomib to ixazomib in patients with multiple myeloma

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Published: 23 Sep 2019
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Dr Habte Yimer - Texas Oncology, Tyler, USA

Dr Habte Yimer (Texas Oncology, Texas, USA) speaks to ecancer at the International Myeloma Workshop 2019 about the transition from bortezomib to ixazomib and how real-world evidence can support this. 

Dr Yimer begins by outlining the current status of multiple myeloma as a chronic cancer, despite having a positive trajectory over the last 15 years.

He goes on to describe the transition of patients from injectable drugs to an oral agent, what this means for patient therapy duration.

Dr Yimer advises on timings for this transition, as well as providing advice for a treatment strategy for clinicians.

This programme has been supported by an unrestricted educational grant from Takeda Pharmaceutical Company

Even though we have made a lot of progress in the last 10-15 years in improving overall survival in multiple myeloma patients, unfortunately it is still an incurable disease. So we are looking at it as a chronic cancer or chronic illness that needs chronic maintenance treatment after the induction phase of the treatment.

How does the real-world evidence support the transition from injectable drugs to ixazomib or an oral regimen to prolong duration of therapy?

That’s a very good question. The reason we decided to do the US MM06 [?] trial, which transitions the injectable form of proteasome inhibitor with bortezomib to an oral agent with ixazomib, is most of the time in the real world setting the benefit that you see from prolonged PI based treatment doesn’t translate into the community. There are a lot of reasons for that: one is patient adherence issues because of different reasons – they might live far away from the cancer centre. It’s quality of life issues too – they don’t want to get an injection as compared to taking oral medication. Financial reasons and also side effects from the medications, including neuropathy from bortezomib, long term is a real problem. So if we transition this patient to a less toxic medication and easy to take medication we think patients will stay longer on therapy. When they stay longer on therapy they’ll get all the benefits they would get from PI-based treatment.

When should clinicians make this transition?

In our study, our study is preliminary, it’s still ongoing right now but when we decided to make the transition is after three cycles. The way we did the MM06 [?] trial is patients who are transplant ineligible they will get bortezomib-based treatment, it could be a triplet treatment or it could be a doublet treatment, and after they have achieved stable disease or better after three cycles of treatment we decided to switch them to ixazomib-based treatment. The reason we did that is most of the neuropathy you start seeing on the bortezomib-based treatment around the third or fourth cycle. The other thing is we want to capture the patients that might start on therapy while in the hospital. So, based on our study, we chose after three cycles.

How safe and effective is this transition?

Ixazomib in combination with Revlimid dexamethasone is already approved for treating recurrent multiple myeloma patients. In a randomised phase III trial it has been shown to be better than Revlimid dexamethasone in recurrent multiple myeloma patients. It has shown to be safe and effective in that setting. So we’re just taking that regimen into the frontline setting.

How can clinicians decide on an effective treatment strategy, based on current available data?

It’s good that we have a lot of active triple and double regimens that are available to use in treating newly diagnosed multiple myeloma patients. There are a lot of factors that we take into consideration – what to use first, when to use it – and this includes the patient performance status, whether they’re a candidate for transplant or not, the risk – whether they are high risk or low risk based on their cytogenetic abnormalities in the myeloma cells. You take all of this into consideration and decide what kind of regimen you use. If they are transplant ineligible candidates then the goal is to keep them on some sort of treatment, even after the induction phase you keep them on a maintenance treatment for a long time until progression. So it’s better to have a less toxic medication and more convenient to take if they are going to be on it for many years. So our data hopefully, if it holds up in the future, will be one of the options to keep them on long-term therapy.