IMS 2025 | The GAH scale: identifying patients with myeloma suitable for intensive regimens

The Spanish group developed a geriatric assessment of hematologic patients, or in other words, the GAHscale. And it’s a frailty assessment that with a cutoff of 42 points or less is a tool to predict lower toxicity in patients with hematologic malignancies. In this sense, the Spanish Myeloma Group developed a clinical trial, the GEM2017FIT trial, validating this geriatric assessment, including transplant-ineligible patients ranging between 65 and 80 years with a GAH scale of 24 or less points. In this trial, the control arm VMP alternating with RD was compared with Dara-KRD or KRD, the experimental arms. The clinical trial met its primary endpoint and the experimental arms achieved significantly higher minimal residual disease negativity after induction. However, DARA-KRD showed significantly higher and acceptable toxicity, understood as treatment-related death or treatment-related discontinuation. Based on this background, we wonder if the GAH scale could predict this unacceptable toxicity. For this, we perform a ROC analysis and we establish an optimal cutoff of 19 points of this scale. For this analysis, we divide the cohort into two groups. Ultrafit patients with a GAH scale lower than 20 and fit patients with a GAH scale over 20. Overall half of patients presented ultrafit status and no difference were observed between treatment arms and fitness status. It’s important to mention that in the ultrafit patients treated with Dara-KRD presented significantly lower and acceptable toxicity, 7%. However, the fit patients treated with the same regimen presented an important toxicity of 17%. It’s important to mention also that patients of the other treatment arms did not present this significant difference. Regarding the efficacy, ultrafit patients treated with Dara-KRD presented significantly higher minimal residual disease after induction, 70%, significantly higher than fit patients with the same regimen, 50%. And also, ultra-fit patients who received Dara-KRD presented significantly higher minimal residual disease than ultra-fit patients treated with the remaining regimens. To conclude, the GAH scale could predict patients who can receive more intensive treatment. And in this regard, patients with a GAH scale less than 20 points is a tool to identify patients suitable for quads. A key point is if we can improve the GAH scale to expand the access to quads therapy. From the hypothetical point of view, the GAH scale could be improved with nutritional and physical interventions because the nutritional status and the physical activities of daily living are the more common affected dimensions of the GAH scale in the patients included in the study. 50% of the patients were deficient in nutritional status and 50% had an impairment on physical activities of daily living. In contrast, other dimensions were not modifiable like polypharmacy or cognitive status. For instance, for example, in the Dara-KRD with targeted intervention in nutritional status, we can improve the scale of 30% of patients and with physical interventions in 20% of patients. The same for the KRD arm. Nearly 40% of patients could be improved up to ultra-fit status with the same interventions. And to summarize, nearly half of patients included in the GEM2017FIT trial that presented a GAH score over 20 could be improved up to ultrafit status and benefit from more intensive treatment and tolerate a quadruple regimen.

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