OPTIMUM MUK Nine Trial | Martin Kaiser, MD | ASH 2022

Hello, I'm Martin Kaiser. I'm a haematologist at the Royal Marston Hospital in London and I'm specialized in myeloma where I also do research at the Institute of Cancer Research in London. I had the pleasure on behalf of my co-investigators at this meeting to present an updated analysis of our optimum MAK9 trial. This is a trial that we designed in the UK with patient input as a collaborative community exercise to address the unmet need of patients with ultra-high-risk myeloma. We're all aware of patients that are treated with standard of care treatment and do relapse early, often just a year after transplant, and these patients have an high unmet need. So we were hoping when we were designing the trial that by diagnosing them early but also by adapting therapy, we can prevent their disease becoming uncontrollable faster. We all know that these patients are very difficult to rescue. So in the optimum trial we wanted to really provide access to this trial for a lot of patients around the country and we all know there may be discrepancies in terms of access to molecular diagnostics in more community settings. So we included a screening protocol to this trial. We opened the trial in 39 NHS hospitals across the UK. Smaller hospitals were the predominant hospitals in the UK called district generals. So really community settings to send samples of patients that were newly diagnosed or had just a suspectus diagnosis of myeloma to a central laboratory where we tested the material for presence of two or more high-risk cytogenetic abnormalities or the Scan Institute gene expression risk profile. And if they were identified as high-risk by having either of the two, we offered participation in the interventional trial to these patients. So of 138 patients that we identified out of 472 screened across the country, we ultimately enrolled 107 into the treatment protocol and there they received not only intensified induction therapy with DARA-C-VRD and a transplant but very importantly prolonged consolidation with DARA-VRD for in total 18 cycles. And this was now an updated analysis on the outcome after these 18 cycles with a median follow-up of over 40 months. All patients had completed the complete consolidation therapy and we did find that the progression-free survival rate at 30 months, so after completion of consolidation two, was 77%. This trial was actually comparing this value against a molecularly matched group of ultra-high risk patients from the myeloma 11 trial where the rate was below 50%. So we're really seeing a very strong difference between PFS outcomes between the two trials and that difference has over time now increased. What was very encouraging to see was that we also saw a very encouraging early overall survival signal. This was our big concern. If these patients get all of these combination therapies upfront, might their overall survival maybe be impacted by what they can then receive at relapse? But we're seeing also on that front an improvement in the signal with over 80% overall survival at 30 months for the optimum trial. So these are very encouraging results and we feel they already make a very strong case for the combination therapy. We generated this data actually to provide an access discussion for patients, particularly as this regimen generally can be delivered in a relatively uncomplicated fashion with only subcutaneous and oral medications. And we're currently working on building a case for access for high risk patients in public healthcare systems to such more personally tailored therapies.