Age Is the Strongest Independent Prognostic Factor in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation: Moffitt Cancer Center Experience
Authors: Paoletti Costanza , Balducci Lodovico , Boler Ivette , Popa-McKiver Mihaela , Externann Martine , Raychaudury Jyotishankar , Anasetti Claudio , Fernandez Hugo F. , Sullivan Daniel , Dalton William S. , Field Teresa , Ayala Ernesto , Kharfan-Dabaja Mohamed A , Perez Lia , Perkins Janelle , Janssen William E. , Harris John , Schell Michael , Kapoor Rachna , Alsina Melissa , Ochoa-Bayona J. Leonel 
Published: April 2020

Abstract
Autologous stem cell transplantation (ASCT) has been demonstrated to prolong survival of Multiple Myeloma (MM) patients, but the benefit of this therapy for elderly patients has not been well established. Randomized data is available for patients up to 65 years of age; however, older patients have been offered autologous SCT provided they fulfill criteria for fitness at different institutions. We conducted a retrospective analysis of 214 MM patients treated with ASCT at our institution from 2001–2006. The objective of this study is to determine if age is a prognostic factor for overall survival (OS) and progression-free survival (PFS) in this patient population. Eight potential risk factors along with 3 age variables (≥65, ≥70 or age in years) were studied using backward elimination (BE) Cox model for the age terms. Age ≥ 65 was the best variable for OS and PFS, with the other two age terms dropping out. We examined 8 parameters [e.g gender, stage at diagnosis, lines of therapy, disease status at the time of transplant, conditioning regimen, time from diagnosis to transplant, and HSCT-comorbidity index and CIRS-G index, to account for co-morbidity] and clinical outcomes [e.g. length of hospital stay (LOS), time to neutrophil engraftment, PFS, and OS]. PFS and OS were calculated from the time of transplant to the time of event occurrence. One-hundred and ten patients (45 female, 65 male), with median age 68 (range 65–77) were ≥65 years (old cohort). One hundred and four patients (46 female, 58 male) with a median age 55 (range 36–64) were &lt;65 years (young cohort). The proportion of patients for several parameters for the old vs the young cohorts, respectively, is as follows: Durie-Salmon stage III (68 vs 81%), 1 line of therapy before transplant (66 vs 74%), disease status prior to conditioning regimen [CR + VGPR(22 vs 20%), PR (53 vs 51%), SD+ PD (25 vs 29%)], median time from diagnosis to transplant was 9 (range 2.2–210) vs 11.5 (2.6–112) months. Conditioning regimens were melphalan alone (63 vs 79%) or melphalan plus other drugs (37 vs 21%). The mean LOS was 22 days (range 0–60) and 19 (range 0–41) and the mean time to neutrophils &gt;0.5 × 109/L was 12 days (range 6–40 and 9–21) for both cohorts. Transplant-related mortality was (4.7 vs 1.9%) and response to transplant was [CR + VGPR (33 vs 40%), PR (31 vs 24%), SD+ PD (28 vs 29%)]. Median PFS was 14.8 months (range 12.3–20.3) and median OS was 36.8 months (range 29.4–46.8) for the old cohort. Median PFS was 24.4 months (range 16.6–31.5) and median OS was 47.9 months (range 43.8–74.3) for the young cohort. Male gender (HR1.8, 95%CI 1.7–2.8, p=0.0075), HSCT co-morbidity score (HR 1.11, 95%CI 0.9–1.2 p=0.06) were negative prognostic factor for OS, and age ≥65 was found to be the strongest negative prognostic factor influencing OS (HR 2.03, 95%CI 1.3–3.1, p=0.0014) and PFS (HR 1.86, 95%CI 1.3–2.7, p=0.0008).
CONCLUSION: ASCT remains a feasible and safe therapy for elderly for multiple myeloma patients, but our experience suggests that age significantly influences PFS and OS in this population.