Validation of the Gatmo Score in Predicting Mortality Following Autologous Hematopoietic Cell Transplant in Multiple Myeloma Patients

Introduction: Autologous Hematopoietic Cell Transplant (AHCT) is incorporated into standard of care management of Hodgkin’s lymphoma (HL), Non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM) as well as other types of malignancies. However, AHCT is an aggressive treatment modality, relying upon high dose chemotherapy. Treatment places significant stress on the body and may increase the non-relapse mortality risk in patients with comorbidities; thus, only patients that meet pre-specified eligibility criteria are considered for the procedure. Recently, the Grupo Argentino De Transplante De Medula Osea (GATMO) proposed a scoring system that categorizes HL, NHL and MM patients into risk categories to predict their overall survival (OS) and non-relapse mortality (NRM) post-AHCT. Here, we aim to validate the GATMO score in our internal cohort of MM patients.

Methods: All MM patients who underwent AHCT at Cleveland Clinic between 2011 and 2021 were screened for our study. Data pertaining to patients’ demographic, cytogenetic, and clinical characteristics were collected via retrospective chart review, including age at AHCT, gender, as well as list of comorbidities as suggested by the hematopoietic cell transplant-comorbidity index (HCT-CI). GATMO risk scores were calculated through the summation of the following: 1 point if male gender; 1 point if age 55 to <65; 2 points if age ≥ 65; 1 point if HCT-CI ≥3. Accordingly, patients were classified as low risk (LR) if their GATMO score was 0-1, intermediate risk (IR) if their score was 2-3, and high risk (HR) if their score was 4.

Results: A total of 513 MM patients who underwent AHCT and with appropriate data available for score calculation were included in this study. They had a median age at diagnosis of 59.3 years, a median age at AHCT 61.4 years, were 57.9% male and 83.2% of White ethnicity, and were followed for a median of 32.9 months post-AHCT. Age group 55 to <65 included 230 (44.8%) patients and age group ≥ 65 included 169 (32.9%) patients. Current smokers were 24(4.7%), Ex-smokers 168 (32.9%) and never smokers 318 (62.4%). Time to transplant was ≥12 months in 150 (29.2%), while the ECOG performance status was 0 in 157 (30.7%), 1 in 318 (62.1%), 2 in 36 (7%) and 3 in 1 (0.2%). ISS stages I, II, and III were determined in 160 (37.7%), 165 (38.9%) and 99 (23.4%), respectively. HR cytogenetics were seen in 134 (32.6%). Pre-AHCT, 314 (66.5%) had received 1 line of therapy, 111 (21.6%) had received 2 lines of therapy, and 61 (11.9%) had received ≥3 lines of therapy. Remission status at AHCT was PR in 208 (40.5%), VGPR in 174 (33.9%) and CR in 131 (25.5%). Components of the HCT-CI index included arrhythmia (10.5%), nonvalvular cardiac (10.9%) and valvular cardiac (1.8%) disease, inflammatory bowel disease (IBD) (0.8%), diabetes mellitus (DM) (13.3%), cardiovascular disease (CVD) (2.7%), psychiatric disease (21.6%), mild hepatic (1.2%) and severe hepatic (0.2%) disease, body mass index (BMI) ≥35 (17.7%), infection at AHCT (3.3%), rheumatological disease (1.6%), peptic ulcer disease (PUD) (0.4%), kidney disease requiring dialysis or creatinine ≥2 (7.4%), mild (33.7%) and severe (20.9%) pulmonary disease, and history of solid tumors requiring treatment (6.8%). The median HCT-CI was 2 (range 0 to 12). Per GATMO score calculation, 137 (26.7%) patients were classified as LR, 335 (65.3%) as IR, and 41 (8%) as HR for mortality post-AHCT. Baseline characteristics including the HCT-CI constituents pertaining to the patients of each risk group are presented in Table 1. Kaplan-Meier analysis asserted the significant difference in survival amongst the 3 risk groups, with median OS 48.5 vs 86.6 vs unreached months (P=0.0017) for the HR, IR and LR groups, respectively (Fig 1). This was further corroborated by the lower time to NRM (medians undefined, P=0.02) and higher 5-year mortality rates (34.1 vs 20.3 vs 15.3%, P=0.03) rates for HR as compared to the IR and LR groups, respectively. There was no significant difference noted in mortality at 1-year (4.9 vs 4.8 vs 2.2%, P=0.4) or 3-year (19.5 vs 14.6 vs 10.9%, P=0.3) intervals post-AHCT.

Conclusion: The GATMO scoring system reliably identifies MM patients who are pre-selected for ASCT but at a higher risk of non-relapse related mortality following the procedure. Hence, risk stratification per the GATMO score may guide decision making in MM patients undergoing AHCT candidacy while predicting their mortality risk based upon pre-AHCT comorbid conditions.