Autologous HSCT effective, safe for older adults with multiple myeloma
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Autologous hematopoietic stem cell transplant conferred favorable 2-year outcomes among older adults with multiple myeloma, according to study results presented at TCT Meetings Digital Experience.
The regimen also appeared safe for the selected population, which included patients aged 75 years or older.
“Patients with newly diagnosed multiple myeloma should be referred for consideration of consolidative therapy with [autologous HSCT] regardless of their age, as specialists can then determine true eligibility based on their comorbidities and also their physical function,” Pashna N. Munshi, MD, associate clinical director of the stem cell transplant and cellular immunotherapy program at MedStar Georgetown University Hospital and assistant professor of oncology at Georgetown University School of Medicine, told Healio.
“Our study was lacking data on frailty and physical function components, which are important tools in making treatment decisions in geriatric populations,” Munshi added. “However, denying someone an effective treatment solely on their age is not recommended.”
The median age of multiple myeloma diagnosis is 70 years.
Autologous HSCT is an effective and safe treatment strategy. However, clinical trials often restrict autologous HSCT to patients aged younger than 65 or 70 years, and many clinicians do not consider this treatment approach for older patients due to concerns about frailty or perceived ineligibility.
Prior studies have suggested autologous HSCT is safe for older patients and associated with encouraging response rates; however, the utilization rate and outcomes among those aged 75 years or older have not been well-established.
Munshi and colleagues examined outcomes of patients aged 75 years or older who underwent first autologous HSCT within 12 months of multiple myeloma diagnosis in the United States between 2013 and 2017, in the era of routine use of proteasome inhibitors and immunomodulatory agent induction.
They evaluated disease relapse or progression, PFS and OS.
Researchers also sought to identify transplant utilization rates in this population, evaluate the impact of melphalan dose and identify other factors associated with outcomes.
The analysis included 360 patients (median age, 76.3 years; range, 75-83; 63% men; 84% white), the majority of whom had Karnofsky performance score less than 90 (56%), Hematopoietic Cell Transplantation-specific Comorbidity Index of 3 or higher (57%) and International Staging System stage III disease (53%).
About one-third (32%) of patients had high-risk cytogenetics. All patients received peripheral blood stem cell grafts and melphalan conditioning (71% dosed at 140 mg/m2), and more than half (57%) demonstrated a very good partial response or better at the time of transplant.
Median follow-up was 24 months (range, 3-63).
Univariate analysis showed a 100-day transplant-related mortality rate of 1% (95% CI, 0-2) and a 2-year rate of 6% (95% CI, 4-10). At 2 years, 27% (95% CI, 22-33) had relapsed, whereas 66% (95% CI, 60-72) remained progression free and 83% (95% CI, 78-87) remained alive.
Multivariate analysis showed high-risk cytogenetics was the only factor associated with increased risk for relapse (HR = 2.15; 95% CI, 1.29-3.58) and shorter PFS (HR = 1.63; 95% CI, 1.04-2.57).
Age at transplant had no impact on OS.
“We were pleased to see that [autologous HSCT] for multiple myeloma remains feasible in this older population and is tolerated without increase in transplant-related mortality compared with historical data,” Munshi said.
Researchers reported higher transplant utilization rates during the study period for white men aged 75 years or older (5.19% to 5.84%) than Black men of the same age (3.53% to 3.97%; P = .02). Results showed a similar disparity in utilization rates between white women (3.37% to 3.79%) and Black women (1.88% to 2.12%; P < .01).
“This study has [a] limitation in that we don’t know reasons for [sex or race disparities] in the utilization of [autologous HSCT for patients with multiple myeloma] in this age group,” Munshi told Healio. “We can only offer hypotheses that there are likely referral biases, access issues or even patient biases on receiving more ‘aggressive’ therapies.”
Efforts to support and perform research in this area helps identify barriers to treatment, Munshi added.
“Hopefully this motivates referring providers and payers to not negate the benefits of standard therapies based on age alone,” she said. “The racial and gender disparity is now actively studied in many malignancies, yet knowledge gaps remain. Educators, outreach and support groups can be key players in helping the transplant community highlight these deficiencies.”
Munshi and colleagues acknowledged additional study limitations, including its highly selected population, the fact data do not capture outcomes of patients who delayed transplant beyond 12 months from diagnosis, the lack of details about maintenance regimens, and the lack of information about pre-HSCT geriatric assessments and quality of life.
“Research to support these objective assessments of frailty and physical function [among elderly patients with multiple myeloma] receiving aggressive therapies like [autologous HSCT] is underway,” Munshi said. “Using standardized tools can further guide clinicians into making informed treatment decisions for their elderly patients.”
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Munshi PN, et al. Abstract 49. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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