EMN 2021 | Frailty subgroup analysis of the MAIA trial
Gordon Cook, MB ChB, PhD, FRCP(Glas), FRCPath, Leeds Teaching Hospitals NHS Trust, Leeds, UK, discusses results from a frailty subgroup analysis of the MAIA trial (NCT02252172). The MAIA trial tested the benefit of adding daratumumab (D) to lenalidomide plus dexamethasone (Rd) in transplant-ineligible myeloma patients. Prof. Cook describes the use of a modified version of the IMWG frailty score which incorporated age, Charlson Comorbidity Index and baseline Eastern Cooperative Oncology Group Performance Status score. The analysis found that, with regards to progression-free survival (PFS), addition of D to Rd was beneficial both in patients who were frail and in patients who were not frail. This interview took place during the 2021 European Myeloma Network (EMN) congress.
Transcript (edited for clarity)
The MAIA trial was in transplant non-eligible patients and was testing the benefit of adding the CD30-directed antibody daratumumab to lenalidomide dexamethasone, so it’s a late phase, Phase III study of daratumumab-len-dex versus len-dex for frontline therapy. And what has been presented at the European Myeloma Network meeting is actually the frailty subgroup.
Now, the IMWG frailty score used age, co-morbidity and two functional assessments, the ADL and IADL, which are time-consuming, often difficult and sometimes subjective in their measurements, but more importantly, you can apply these retrospectively to trial cohorts and Thierry Facon and colleagues developed a modified version of IMWG where they used, or they tested actually, the EQ-5D module, or WHO performance score, and found that both were equally as valid...
The MAIA trial was in transplant non-eligible patients and was testing the benefit of adding the CD30-directed antibody daratumumab to lenalidomide dexamethasone, so it’s a late phase, Phase III study of daratumumab-len-dex versus len-dex for frontline therapy. And what has been presented at the European Myeloma Network meeting is actually the frailty subgroup.
Now, the IMWG frailty score used age, co-morbidity and two functional assessments, the ADL and IADL, which are time-consuming, often difficult and sometimes subjective in their measurements, but more importantly, you can apply these retrospectively to trial cohorts and Thierry Facon and colleagues developed a modified version of IMWG where they used, or they tested actually, the EQ-5D module, or WHO performance score, and found that both were equally as valid. So, you can use age, co-morbidities and performance score to define people as being fit or unfit.
And this frailty subgroup analysis and MAIA is using that same strategy, being able to delineate patients who are fit or frail basically. And the bottom line is that what they showed for us, particularly for the PFS, is that for patients who are non-frail, then again, daratu-len-dex shows a superior PFS, but equally in patients who are frail, there is an uplift in the PFS significantly for those who receive dara-len-dex.
Now, what’s interesting for me is that if you look at the non-frail patients who got len-dex, they actually don’t do quite as well, albeit it it’s subtle, as the frail getting dara-len-dex, so dara-len-dex does better if you’re frail than len-dex, if you’re non-frail. Now, the difference here is subtle and it’s not going to be statistically significant, but it does indicate that you can deliver this triplet regimen to frail patients, and they will, A, do better than the doublet in the frail patient group, and B, they actually are performing slightly better than the doublet in the non-frail group.
So, it’s very interesting data. It’s a post-trial subgroup analysis, so you can’t be dogmatic about the results, but what I think they do is show a nice trend that’s worthy of pursuing, because there is this feeling that for frail patients, then only doublets are the way to go, where in actual fact what this shows is that actually that’s not necessarily the case. And it gives very, very good groundwork to start designing some prospective clinical trials where you can actually incorporate that into your thinking.
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