Although clinical trials have shown benefit of continuous proteasome-based inhibitor treatment in multiple myeloma, it is challenging to achieve an ongoing treatment in the real world. The median treatment duration is often shorter in routine clinical practice than what we see in clinical trials. The US MM-6 is investigating a novel in-class transition approach in US community populations with the aim to increase the PI-based treatment adherence and duration while also maintaining quality of life and further improving outcomes.
US MM-6 is a community-based real world open label single arm phase IV study. Eligible patients are newly diagnosed multiple myeloma patients who are not transplant eligible. They receive first line bortezomib-based induction and after three cycles, as long as they do not have disease progression, they are enrolled and proceed with the in-class transition to an all oral ixazomib lenalidomide and dexamethasone regimen.
This study is also employing a novel data collection methodology to evaluate patient reported outcomes and actigraphy data too.
The primary endpoint is a two year progression free survival and then the key secondary endpoints are response rates, duration of responses and also looking at the actigraphy and electronic patient reported outcome data too.
At the data cut-off the total number of patients that will be enrolled will be 160; at the time of data cut-off in November 2019 84 patients had been enrolled. So far the study shows that these patients are already on a prolonged duration of PI-based therapy with a mean duration of 10.1 months. The study also shows that the response rates are evolving. The overall response rate after the bortezomib-based induction of three cycles was around 62% with 4% having a complete response and 25% having a very good partial response. After transitioning to the all oral ixazomib-based regimen we are seeing that the overall response rate is around 70% right now with 26% of these patients having complete response and 29% having very good partial response. So there is a deepening of response. At the preliminary PFS at twelve months we are seeing 86% for IRD, that’s the oral regimen.
The safety profile is as expected with the ixazomib-based regimens. Most of the side effects are predominantly with GI side effects and neuropathy which is expected.
So far, based on the data so far, we are seeing that the patients are already receiving prolonged duration of PI-based therapy and the patients are also having their quality of life maintained. That is, when we looked at the actigraphy data the mean number of steps is around 9,160 steps per day which is similar to the established steps for patients above 65 years or within the range of patients with comorbidities.
We’re also looking at the peripheral neuropathy data and it looks like there is a limited increase in peripheral neuropathy, which is not much compared to the traditional parenteral-based proteasome inhibitor treatments.
So, in summary, we are seeing a prolonged duration of PI-based therapies, favourable safety profiles. Patients’ quality of life is maintained and they are staying as active as they were at the time of treatment initiation.
The enrolment is ongoing right now and we will have more data mature in the next year or so. We should be able to complete the enrolment and present the completed data in the near future.
In conclusion, the US MM-6 study, the data so far is showing that we may be able to prolong PI-based therapy with promising efficacy without impacting the quality of life and that this can be enabled by collecting the data with digital devices.