IMWG /ECOG Frailty Score Was a Good Indicator for ASCT Candidate Selection for NDMM in China from a Hcmmd Retrospective Study
Authors: Wu Xingyue , Fu Chengcheng , Shen Hongmiao , You Hongying , Zhai Yingying , Wang Jing , Yan Zhi , Yan Shuang , Yao Weiqin , Lu Jiao , Shang Jingjing , Jin Song , Shi Xiaolan , Yan Lingzhi , Wu De-Pei 
Published: December 2023

Background
Autologous hematopoietic stem cell transplantation (ASCT) has always been considered as the standard choice for newly diagnosed multiple myeloma (NDMM) patients less than 65 years old, or even older. At present, how to define the patients who is suitable for transplantation is still controversial in clinic in China. Rate of utility of ASCT in front line was as low as 10%. The screening of transplant patients mainly depends on the evaluation of the general condition of patients, the wishes of patients and their families, and the evaluation of organ function by physical examination. In this way, it is particularly difficult for doctors in non-transplant medical units to recommend stem cell transplantation for patients. Based on “HemaTank” Chinese multiple myeloma database(HCMMD), a retrospective study of construction of special disease cohort and prognostic model for multiple myeloma were conducted to explore the posibilities of utility of IMWG/ECOG frailty score to select transplantation candidate, and the prognostic significance of frailty score in all MM patients.
Methods
In this study, 322 NDMM in the first affiliated Hospital of Soochow University from August 2018 to October 2022 were analyzed retrospectively. All patients were valuated with IMWG/ECOG frailty score before each cycle of treatment, which included age, the ECOG score, and the Charlson Comorbidity Index. Patients with IMWG frailty score≥2 were defined as frail, with score &lt;2 were unfrail. Transplant patients received 4 courses of induction of VRd regimen followed by ASCT, and 2 courses of VRD consolidation after transplantation. Non-transplant patients received 8 courses of induction with VRD regimen. Standard risk patients received lenalidomide as maintenance therapy until PD. High risk patients received V+R as maintenance treatment until PD.
Results
The median age of 322 patients was 58(29-79). 178(55.3%) patients were male. 170 (52.8%) patients were unfrail at diagnosis, with a mean age of 56.72±7.11. 77.8% of the unfrail patients were less than 65 years old. 152 patients were frail at diagnosis, with a mean age of 59.47±8.28. 68% of the patients were less than 65 years old. There were statistical differences in age, DS stage, ISS stage and R-ISS stage between the two groups. (P &lt; 0.05). After induction therapy, 246 patients (76%) rescored IMWG/ECOG frailty score before ASCT. 46 patients changed from frail state at first diagnosis to nonfrail before transplantation, mainly because of the improvement of ECOG score and renal function. There is no change from a nonfrail state at the first diagnosis to a frail state when entering the ASCT program. After logistics regression analysis of IMWG/ECOG score, age, renal function and CCI, unfrailty is the best indicator of selection patients as ASCT candidate, OR=0.37, 95%CI 0.21-0.63 (P &lt; 0.001).
At the time of ASCT, there was no significant difference in the ORR of induction therapy between frail and unfrail patients. But the granulocyte and platelet reconstruction during ASCT in the frail group was slower than that in the unfrail group, P&lt;0.0001. The transplantation-related mortality was 0. In this cohort, the PFS and OS of the NDMM patients accepted VRD+transplantation was all better than those received VRD only. Most importantly, the OS of the frail patients scored at the time of ASCT was much poorer (P&lt;0.05) than that of the unfrail group with no significant difference in PFS between two groups. But there were no significant differences in PFS and OS of the patients who changed from frail to unfrail after induction therapy compared with those remained unfrail at diagnosis and after induction therapy.
Conclusion
IMWG/ECOG frailty score can be used to select ASCT candidate for NDMM patients. In the study 144 patients (84.7%) remained unfrail at diagnosis and before transplantation accepted ASCT. and 46 frail patients (30.2%) at diagnosis transferred from frail to unfrail after induction and accepted transplantation. It was suggested that the IMWG/ECOG frailty score evaluated before transplantation is more instructive for long-term overall survival. The OS of unfrail patients was better than that of frail patients even with no significant difference in PFS.