Impact of Combining Frailty Assessment Systems to Select Elderly Myeloma Patients Eligible for Autologous Peripheral Blood Stem Cell Transplantation
Authors: Tanimura Akira , Okazaki Koji , Okuda Yuko , Hirai Risen , Kudo Daisuke , Takeshita Masataka , Miwa Akiyoshi 
Published: November 2019

Introduction
The International Myeloma Working Group (IMWG)-frailty index (IMWG-FI) and revised myeloma comorbidity index (R-MCI) are multiple myeloma (MM)-specific frailty scoring systems, which the European Myeloma Network advocates to assess patient frailty, and to select goals and treatments including autologous stem cell therapy (ASCT).
In Japan, patients <65 years old are recommended to receive ASCT under the guidelines of the Japanese Society of Hematology, The Japan Society for Hematopoietic Cell Transplantation, and Japanese Society of Myeloma. However, some Japanese institutes perform ASCTs on MM patients ≥65 years old, although the eligibility criteria and the ASCT methods are variable, or depending on the attending physicians' experience and preference, and doctor-patient relationships.
In our institute, 17 MM patients ≥65 years old received ASCT and their frailty at the time of ASCT was retrospectively analyzed.
Methods
We performed 51 ASCTs on 43 MM patients between April 2017 and June 2019. Seventeen patients were elderly, and 34 were younger. The conditioning regimens were melphalan 200 mg/m2 for younger and 140 mg/m2 for the elderly patients. Both groups received the same supportive therapy.
Frailty was compared using the IMWG-FI, R-MCI, and Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), and the toxicity and efficacy of ASCT were retrospectively analyzed.
Results
The patients' ages at the time of ASCT were statistically different between groups (67.8 vs 57.8 years old, p<0.001). The number of fit and intermediate-fit patients by IMWG-FI were 14 and 3 in the elderly group, and 28 and 6 in the younger group, respectively (p=1.0). Fit and intermediate-fit patients by R-MCI were 13 and 4 in the elderly group, and 27 and 7 in the younger group, respectively (p=1.0) (Table 1). No patients were classified as frail in either group by the IMWG-FI and R-MCI.
The median scores (ranges) of HCT-CI were 1 (0-5) in the elderly group, and 1.5 (0-5) in the younger group (p=0.93).
The number of CD34 positive cells harvested from peripheral blood was lower in the elderly than in the younger group (3.8 vs 5.4×106/kg, p=0.0027). For the elderly and younger groups, the infused CD34 positive cell count (2.4×106 vs 2.4×106/kg, p=0.87), days for neutrophil (11 vs 11 days, p=0.87) and platelet engraftments (15 vs 15 days, p=0.7), and the hospitalization periods (26 vs 27 days, p=0.27) were not statistically different.
Both groups had no transplantation-related deaths, similar rates of the non-hematologic adverse events (grade ≥3), an improvement in response (≥very good partial response (VGPR); 49% vs 74%, p=0.003) before vs after ASCT. Post-ASCT ≥VGPR rates were similar between the elderly and younger groups (73% vs 75%, p=1.0).
Discussion
We safely performed ASCT for elderly MM patients. The frailty status of the younger and elderly groups were the same, as evaluated by the IMWG-FI, R-MCI, and HCT-CI. Our eligibility criteria for MM patients for ASCT was by biological and not chronological age. Thus, the prospective assessment of elderly MM patients by these tools may enable us to evaluate the risks of elderly ASCT, through which elderly ASCT-eligible cases can be selected.
Eleven of the 17 elderly patients were termed fit by the IMWG-FI and R-MCI, and scored 0-3 by HCT-CI, 6 of whom were 0-1. Five patients were intermediate-fit by either IMWG-FI or R-MCI, with 0-3 by HCT-CI. Only 1 patient was intermediate-Fit by both IMWG-FI and R-CMI, and was 5 by HCT-CI (Table 1).
Based on our data, we propose a stratification system that can determine ASCT eligibility in elderly MM patients. The elderly patients regarded fit by IMWG-FI and R-MCI with 0-1 by HCT-CI could be stratified as Low Risk for elderly ASCT. In addition, the frail patients by IMWG-FI or R-MCI or >3 by HCT-CI could be stratified as High Risk ineligible for elderly ASCT. Other patients could be Intermediate-Risk for elderly ASCT.
Further studies are needed to determine the adequate melphalan dosage such as 200 mg/m2 for 65-69 year-old patients, and 140 mg/m2 for 70-
Conclusion
We retrospectively analyzed the elderly patients receiving ASCT using two MM-specific frailty indices and HCT-CI. We propose a new stratification system to select elderly patients eligible for ASCT. ASCT issues for the elderly MM patients should be examined prospectively.

Disclosures
No relevant conflicts of interest to declare.