FiTNEss: Investigating frailty-adjusted therapy in transplant non-eligible patients with NDMM

Prof David Cairns - University of Leeds, Leeds, UK

The FiTNEss study is fully titled Frailty Adjusted Therapy in Transplant Non-Eligible Patients with multiple myeloma. It’s a UK Myeloma Research Alliance study, Myeloma XIV. Outcomes for multiple myeloma patients have improved in the last twenty years with the advent of immunomodulatory agents and proteasome inhibitors but there still remains a challenge in delivering therapy to older patients. In our last study, Myeloma XI, patients who were older received less therapy, they had more dose modifications and they ceased treatment earlier than their protocol specified amount of treatment. But calendar age isn’t the only element which affects the amount of therapy which you can deliver to a patient, frailty is probably a better measure of how much treatment can be delivered to a patient.

The International Myeloma Working Group a few years ago derived a frailty score which classifies patients as fit, intermediate fitness or unfit based on their calendar age and their comorbidities and their activities of daily living, their function. So you can have an older patient who is still very active, has very few comorbidities and they can tolerate treatment well whereas a younger patient who is unfit perhaps cannot tolerate treatment so well.

So we decided, in the UK Myeloma Research Alliance, to design a study for older patients where rather than give everybody the same treatment up front we would use this International Myeloma Working Group frailty score to tailor the treatment specifically to patients. So in that we’ll give the fit patients the standard dose and then the unfit and frailer patients reduced doses at the beginning. The hypothesis being that if you start patients off on a lower dose they’re better to tolerate it and you’ll be able to deliver a larger total dose over a period of time. We’ll be comparing that in a randomised controlled trial against standard reactive dosing. At the same time every few cycles of treatment we’ll be reassessing patients’ frailty to see if they are becoming less frail and could potentially escalate their treatment or becoming more frail and de-escalate it.

We are giving triplet treatment with ixazomib, Revlimid and dexamethasone and then after twelve cycles of this triplet induction therapy there will be a further randomisation to doublet maintenance as compared to standard of care Revlimid maintenance for patients until disease progression or intolerance.

This study has been in set-up for the last year and it’s due to open in the first quarter of 2020. We expect and hope our first patients in January 2020. We expect to open at around 70 NHS hospitals in the UK following on from our great success of recruitment in our previous study, Myeloma XI.

We would hope that in the future this frailty score or another would be used routinely in the clinic. The IMWG frailty score is slightly cumbersome: you need to complete three questionnaires for the patient. So at the same time we’re testing our own novel frailty score which requires far fewer variables to calculate and therefore could be less cumbersome and more easily used in the clinic. But in the future we expect that frailty assessment will be in common use in the clinic, not just in clinical trials but in standard practice also.