Impact of Obesity in Patients with Multiple Myeloma Receiving High-Dose Melphalan Followed By Autologous Hematopoietic Cell Transplantation

Abstract Background: Chemotherapy administration to obese patients poses significant challenges due to the potential for augmented toxicities. There are limited guidelines and literature available on the dosing of high-dose therapy followed by autologous hematopoietic cell transplantation (HCT) in obese patients and dosing practices vary widely. We conducted a single-center, retrospective cohort study to compare outcomes and toxicities after high-dose melphalan followed by autologous HCT among non-obese (body mass index [BMI] < 30 kg/m2), obese (BMI 30-34.9 kg/m2), and severely obese (BMI ≥ 35 kg/m2) multiple myeloma patients. Patients and Methods: A total of 462 consecutive patients transplanted between January 2004 and December 2011 were included. Patients who had received a tandem transplant and those with the diagnosis of amyloidosis were excluded. The primary endpoint of the study was to compare the incidence of non-relapse mortality (NRM) and overall survival (OS) rates across all three cohorts. Secondary endpoints included progression-free survival (PFS), incidence of relapse, hospital length of stay, hospital readmission rates, engraftment and grade 3 and 4 non-hematologic toxicities. Results: All three cohorts had similar baseline characteristics except for age ≤ 65 years (yrs) (severely obese 85.3%, obese 66.7%, non-obese 63%; p = 0.001), and the use of adjusted body weight for melphalan dosing (severely obese 41.2%, obese 25.7%, non-obese 4.5%; p < 0.0001). Across all three cohorts, there were no significant differences in NRM, relapse/progression, OS, PFS, engraftment, response to transplant, hospital length of stay, 30-day readmission rates, grade 3 to 4 nausea, vomiting, enteritis, or renal toxicity. In univariate analyses, Durie-Salmon Stage (DSS) 3 was the only independent predictor of inferior OS. DSS 3 and ≥ 2 lines of therapy were significant predictors of inferior PFS. In a multivariate analysis, DSS 3 (hazard ratio [HR] 2.28, 95% confidence interval [CI]: 1.01-5.13, p = 0.05), age > 65 yrs (HR 2.13, 95%CI: 1.19-3.82, p = 0.01), serum creatinine (Cr) ≥ 1 mg/dL were associated with higher NRM, whereas actual weight (AW) dosing was associated with decreased risk of NRM (HR 0.38, 95%CI: 0.19-0.72, p = 0.003). Additionally, age ≤ 65 yrs (HR 1.32, 95%CI: 1.03-1.71, p = 0.03), baseline serum Cr ≤ 1.5 mg/dL were associated with increased risk of relapse/progression, whereas disease status ≥ partial response prior to HCT (HR 0.71, 95%CI: 0.54-0.94, p = 0.02) and BMI ≥ 35 kg/m2 (HR 0.62, 95%CI: 0.44-0.87, p = 0.01) were associated with decreased risk of relapse/progression. In a subgroup analysis evaluating only patients with AW dosing of melphalan, febrile neutropenia was more common in non-obese patients compared to obese and severely obese patients (71.4% versus 56.4% and 62.5%, respectively; p = 0.03). Conclusions: High-dose melphalan and autologous HCT can be performed safely in obese myeloma patients and BMI of ≥ 30 kg/m2 does not appear to be associated with adverse transplant outcomes. Further analysis is needed to evaluate the effect of dose adjustments on outcomes. Disclosures Alsina: Onyx: Speakers Bureau; Millenium Pharmaceuticals: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Onyx: Consultancy. Nishihori:Signal Genetics: Research Funding; Novartis: Research Funding.