Optimizing Frailty Tools Are A Vital Component of Improving Care Across Hematologic Malignancies

Nilesh Kalariya, PhD, AGPCNP-BC, AOCNP

Using objective measures such as grip strength and gait speed may help clinicians better predict outcomes for newly diagnosed patients with hematologic malignancies, according to Nilesh Kalariya, PhD, AGPCNP-BC, AOCNP. In addition, for patients with high-risk multiple myeloma, CAR T-cell therapy administered in earlier lines of treatment may play a role in obtaining deeper and durable responses.

Kalariya, who is a nurse practitioner with the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, recently spoke with Oncology Nursing News® about his top takeaways from the 64th American Society of Hematology Annual Meeting and Exposition. He discussed research from the University of Pennsylvania which showed clinical utility of a frailty phenotype tool and contextualized the role of CAR T-cell therapy for patients with multiple myeloma, and whether data from a subgroup analysis of the KarMMa-2 trial (NCT03601078) supports moving it forward in the treatment lineup.^1,2,3

Oncology Nursing News®: What were the abstracts that may have the most impact of oncology nursing practice?

Kalariya: I liked one of abstracts that was about frailty phenotype as a predictive marker for overall mortality in [patients with acute myeloid leukemia] AML and [myelodysplastic syndromes] MDS. [For] patients with a high-risk AML and MDS, with high-risk cytogenetics, overall mortality is high and overall survival [OS] is low—in some cases, it is even less than 10%, which is a significant number, particularly for older patients.

Traditionally, as clinicians, we relied on subjective parameters such as age, disease status, and performance status, but we never considered objective measures to try to predict outcomes. This particular study, from the University of Pennsylvania, used the Fried frailty phenotype tool, and categorized patients at baseline to see whether the patient is a frail, prefrail, or fit patient. Then they studied the mortality and OS [of these patients] and they found that patients who were frail had significantly increased overall mortality, and shorter OS.

When a patient [has] newly diagnosed [disease], we can use this tool to see the chances of survival for this particular patient. That really helps in treatment decisions and overall plan of care.

This particular tool has 5 different components [exhaustion, reported weight loss, activity level, gait speed and grip strength], and 2 of them are objective measures [gait speed and gait strength]. This study provided new data which help us see the importance of objective measures as part of such tools that we could use as marker for mortality and overall OS.

I think this [has implications] not just for AML or MDS, but multiple myeloma as well. We also have a frailty tool for multiple myeloma, but we want to see what kind of objective parameters that we can incorporate, which would really help pinpoint and identify the patients who are at a higher risk. Such tools are instrumental in risk stratification.

Another point is that if we identify any patient as a frail patient, we should also try to look into whether frailty is because of comorbidities or the disease itself. [These represent] 2 different scenarios. Let’s say the frailty is because of the disease—with appropriate treatment, we might see a significant improvement in the frailty, but if the patient is frail because of chronic conditions, we may not see much improvement.

This is another area of interest which is being discussed and explored at this time, and hopefully in the coming few years, we’ll be able to revise and validate predictive tools for clinical utility.

Did any clinical data emerge that may shift treatment for patients with multiple myeloma?

Yes. The KarMMa-2 trial, for [patients with] multiple myeloma treated with [idecabtagene vicleucel (Abecma)], provided robust data which may pave the way for frontline use of Abecma.

Currently, the FDA approval for [idecabtagene vicleucel] is for patients who already had 4 prior lines of therapies. However, this new data provided an evidence [to see] if can use this CAR T-cell therapy in frontline settings.

The [study] had 3 subcohorts in Cohort 2, but the data were presented for only 2 subcohorts: cohort 2a and cohort 2c.

In both of these cohorts, eligible patients had only 1 prior line of therapy, and it was mostly induction followed by stem cell transplant. Patients who had early relapse, meaning a relapse after stem cell transplant within 18 months were part of cohort 2a, and those who had inadequate response after stem cell transplant were part of cohort 2c. They defined these patients as high-risk based on early relapse or inadequate response.

When we look at the data, we find some interesting trends. The complete remission rate, as well as the overall response rate, was better compared with the pivotal study that was published before FDA approved idecabtagene vicleucel. The results from these two subcohorts provided an evidence that use of Idecabtagene Vicleucel in frontline settings may offer a higher number of patients with complete remission, better overall outcome, and also a longer progression-free survival.

If I have to pinpoint one thing [of interest], it’s the results of KarMma-2 cohort 2c which allowed patients to use maintenance therapy after CAR T-cell therapy. We have [seen] remission lasting for up to 2 years based on published data, but we have patients at MD Anderson, who are more than 3 years [posttreatment] and they are still in stringent complete remission. More data will come in near future, but from what we see now, CAR T-cell therapy, followed by maintenance therapy, might be a key in frontline settings to have a longer duration of response for patients with relapsed and refractory multiple myeloma.

References

1. Taborda CC, Gier SH, Stivale AW, et al. Fried’s frailty phenotype predicts mortality and survival for newly diagnosed older patients with acute myeloid Leukemia or high-risk myelodysplastic syndrome. Blood. 2022;140(suppl 1):10825-10827. doi:10.1182/blood-2022-169924
2. Usmani S, Patel K, Hari P, et al. KarMMa-2 cohort 2a: efficacy and safety of idecabtagene vicleucel in clinical high-risk multiple myeloma patients with early relapse after frontline autologous stem cell transplantation. Blood. 2022;140(suppl 1):875-877. doi:10.1182/blood-2022-162469
3. Dhodapkar M, Alsina M, Berdeja J, et al. KarMMa-2 cohort 2c: efficacy and safety of idecabtagene vicleucel in patients with clinical high-risk multiple myeloma due to inadequate response to frontline autologous stem cell transplantation. Blood. 2022;140 (suppl 1): 7441–7443. https://doi.org/10.1182/blood-2022-162615