ASH 2024 | Frailty-based outcomes in patients with multiple myeloma treated with bispecific antibodies

This is an abstract that we presented at the most recent ASH annual conference discussing the outcomes of older patients with multiple myeloma treated with bispecific antibodies at our institution, stratifying the outcomes by frailty status. This is a single institution study. We included patients at least 65 years of age who received bispecific antibodies anywhere from 2018 to 2024, and we divided the patients into two groups, frail and non-frail. Because this is a retrospective study, we used a simplified frailty index, which depends on age, the ECOG performance status, and the Charlson comorbidity index, which is a score for the comorbidities. We had about 99 patients overall. The ages were between 65 and 89, and about a third of the patients were 75 years or more. So among those, we had about 71% of patients who were classified as frail, and a third of patients who would be classified as non-frail using this definition. And when we compared the outcomes between the two groups, we looked at efficacy of the treatment, and we also looked at toxicity, which would include the toxicities that we know of, the CRS, the ICANS toxicity, other neurotoxicities. And we also looked at the unplanned admissions, we looked at the infections, and we looked at the non-relapse mortality, meaning death not from disease. When we compared the two groups, we found really no difference between the two groups in terms of efficacy, and this includes the overall responses and includes also progression-free survival and the overall survival. Now we have to be mindful that the follow-up is short but this is reassuring that frail patients derived similar efficacy compared to non-frail patients. In terms of toxicity, we also did not find a significant difference between the two groups in terms of toxicity, whether it was CRS or ICANS. And we also have to be mindful that the ICANS episodes were also small. So only about five patients, frail patients, had ICANS compared to one non-frail patient. There was also no difference in terms of total days of hospitalization, including unplanned admissions or ED visits. We actually found that early mortality was not different between the two groups. Even early non-relapse mortality specifically was not different. And with early, we mean within 90 days of treatment. Now, as I discussed earlier, the simplified frailty index includes three components: age, Charlson Comorbidity Index, and the ECOG performance status. When we looked at each of the components separately, we found that age and comorbidities using the cutoff scores in the index were not associated with prognosis, whether PFS or OS. However, a poor performance status defined as an ECOG of more than one was actually associated with decreased progression-free and overall survival. And this highlights that performance status is important. We usually recommend getting an assessment of the functional status using patient-reported data and objective assessments like walk tests, grip strength, depending on the resources which are available. But even the physician-assessed ECOG performance status in this case was prognostic. Now, to just summarize the results, what we found is that frailty, at least defined by this index, was not associated with adverse outcomes. And frail patients derive similar benefit from those treatments. And these results are somewhat reassuring because frail patients have been historically excluded from clinical trials including those of immunotherapies, bispecific antibodie, and CAR-T. And with these results hopefully this should provide more reassurance to include older patients but I have to just highlight that again the definition that we use here was the simplified frailty index because we did not assess for frailty in the beginning. So what I can say is that using this definition, frailty was not prognostic, but we really need more information and prospective data in order to identify the subset of patients who is at increased risk of toxicity with those therapies.

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