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Impact of body mass index on outcomes of multiple myeloma patients undergoing upfront autologous stem cell transplant

2024; Wiley; Linguagem: Inglês

10.1111/bjh.19937

1365-2141

Curtis Marcoux, Sarah Pasyar, Denái R. Milton, Hina Khan, Mark R. Tanner, Qaiser Bashir, Samer A. Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Niraj Neupane, Hans C. Lee, Krina K. Patel, Guilin Tang, Yosra Aljawai, Partow Kebriaei, Sheeba K. Thomas, Robert Z. Orlowski, Elizabeth J. Shpall, R. E. Champlin, Muzaffar H. Qazilbash, Oren Pasvolsky,

Chronic Myeloid Leukemia Treatments

Obesity is a rising global health concern and an established risk factor for multiple myeloma (MM).1 The association between obesity and outcomes in MM patients remains controversial, with limited real-world data, especially for patients undergoing autologous haematopoietic stem cell transplant (auto-HCT). Furthermore, body mass index (BMI) is often considered when determining transplant eligibility and is included in the haematopoietic cell transplant comorbidity index (HCT-CI), a tool used for predicting survival post-transplant in MM patients.2 Given its modifiable nature, understanding the impact of BMI on treatment outcomes in MM patients is crucial. Herein, we present outcomes for a large cohort of patients with MM who underwent upfront auto-HCT at our centre between 2000 and 2021, focusing on the impact of BMI on outcomes. The primary end-points were progression-free survival (PFS) and overall survival (OS) and secondary end-points were haematological response and measurable residual disease (MRD) status. Patients were grouped into normal BMI (18.5–24.9 kg/m2, BMI-N) and high BMI (≥25 kg/m2, BMI-H). The BMI-H cohort included overweight (25–29.9 kg/m2), moderately obese (30–34.9 kg/m2) and severely obese (≥35 kg/m2). A total of 2795 patients were included, 609 (22%) with BMI-N and 2176 (78%) with BMI-H. Ten patients (0.4%) were underweight (BMI < 18.5 kg/m2) and were excluded from the analysis. Within the BMI-H group, 1094 (50%) were overweight, 668 (31%) were moderately obese and 414 (19%) were severely obese. Median age of the entire cohort was 61 years (range: 25–83). The most used induction regimen was bortezomib, lenalidomide and dexamethasone (VRD) (758; 27%) and 1871 (67%) received maintenance therapy. Compared to the BMI-N group, those in the BMI-H group were more likely to be male (p < 0.001), younger (p < 0.001), Black (p = 0.012) and had lower R-ISS (p = 0.002), higher comorbidity burden (p < 0.001) and deeper haematological response prior to auto-HCT (MRD-negativity, p = 0.023; ≥complete remission, p = 0.032; ≥very good partial remission, p = 0.017). Baseline patient and disease characteristics are summarized in Table S1. After completing induction therapy and prior to transplantation, ≥complete response (CR) and ≥very good partial response (VGPR) were achieved in 10% and 48% of the patients with BMI-N, compared to 13% and 53% in those with BMI-H, respectively. Day 100 response was ≥CR and ≥VGPR in 29% and 73% of patients with BMI-N compared to 36% and 75% in those with BMI-H, respectively. Best post-transplant response was ≥CR and ≥VGPR in 47% and 83% in the BMI-N group compared to 54% and 84% in the BMI-H group, respectively. Post-transplant, MRD negativity was achieved in 62% of 143 patients in the BMI-N group and 67% of 498 patients in the BMI-H group, among those with available MRD results. Pre- and post-transplant responses according to BMI are depicted in Figure S1. After a median follow-up of 77.1 months (range: 0.23–262) for the entire cohort, the median PFS in the BMI-N group was 38.6 months (95% CI 34.6–43.5) and in the BMI-H group was 41.0 months (38.6–43.9) (p = 0.14, Figure 1A). The median OS was 113.3 months (98.6–128.3) in the BMI-N group and 101.5 months (96.1–106.2) in the BMI-H group (p = 0.61, Figure 1B). Within the BMI-H group, there was no significant difference in PFS (overweight p = 0.10, moderately obese p = 0.26, severely obese p = 0.63) or OS (overweight p = 0.64, moderately obese p = 0.88, severely obese p = 0.24) compared to the BMI-N group. Similarly, BMI was not associated with PFS (hazard ratio [95% CI] 1.0 [0.99–1.00], p = 0.34) or OS (1.0 [0.99–1.01], p = 0.45) when evaluated as a continuous variable. In multivariable analysis, elevated BMI was not associated with either PFS (0.95 [0.85–1.07], p = 0.40) or OS (1.15 [0.97–1.36], p = 0.11). In multivariable analysis for PFS (Table S2), year of transplant ≥2010 (p < 0.001), use of post-transplant maintenance therapy (p = 0.023) and achieving MRD-negative CR as best response post-transplant (p < 0.001) were associated with better PFS. Having clonal lambda (p < 0.001) light chain, with kappa as a reference, high-risk cytogenetics (p < 0.001), R-ISS II (p = 0.036) or R-ISS III (p < 0.001) with R-ISS I as a reference were associated with worse PFS. In multivariable analysis for OS (Table S3), achieving CR at best haematological response (p < 0.001) and the use of post-transplant maintenance therapy (p < 0.001) were associated with better OS. Having clonal lambda light chain (p = 0.029) with kappa as a reference, high-risk cytogenetics (p < 0.001), and R-ISS II (p = 0.031) or R-ISS III (p = 0.001) with R-ISS I as a reference, HCT-Cl >3 (p = 0.003), were associated with worse OS. Univariable analysis of PFS and OS is shown in Tables S4 and S5 respectively. Few studies have explored obesity's impact on MM treatment outcomes. A meta-analysis of prospective studies from 1976 and 2002 demonstrated an association between elevated BMI and mortality in MM.3 Conversely, a study of U.S. Veterans diagnosed between 1999 and 2009 showed lower mortality in overweight or obese patients, but lacked data on disease, treatment, response parameters and auto-HCT status.4 A recent CoMMpass registry study of 1120 newly diagnosed MM patients (46% underwent auto-HCT) showed a trend towards higher progression (HR 1.29; 95% CI: 0.99–1.67) and death (HR 1.43; 95% CI: 0.98–2.08) in severely obese patients (N = 133; 12%) compared to normal BMI.5 Survival differences in severely obese patients were attributed to worse performance status relative to those with normal BMI (58% vs. 43% with ECOG ≥1 respectively), potentially leading to less intense chemotherapy. Severely obese patients were younger (61 vs. 63 years, p = 0.026) with similar comorbidity and frailty scores, yet fewer were considered transplant-eligible (32% vs. 45%). It is unclear if BMI independently affected transplant eligibility. Data on the impact of obesity on outcomes of MM undergoing auto-HCT are even scarcer. In a secondary analysis of the BMT CTN 0702 (STaMINA) trial (N = 549), neither visceral obesity (measured by waist-to-hip ratio) nor BMI was significantly associated with survival outcomes.6 Similarly, a Centre for International Blood and Marrow Transplant Research (CIBMTR) study of 1087 MM patients found no significant association between BMI and PFS, OS or non-relapse mortality (NRM). In contrast to our study, the CIBMTR study included patients who were transplanted between 1995 and 2003, a period when contemporary anti-myeloma drugs such as proteasome inhibitors and immunomodulatory drugs were not available.7 A single-centre study of 462 patients who underwent auto-HCT between 2004 and 2011 also found no difference in PFS, OS or NRM between non-obese and obese patients, though BMI ≥35 kg/m2 was linked to a lower relapse risk (HR 0.62, p = 0.01).8 In contrast, a Russian report of 99 MM patients who received auto-HCT found inferior PFS in obese individuals compared to those with normal BMI (3-year PFS 33% vs. 69%, p < 0.05).9 The last two studies were only published as abstracts; therefore, many patient and treatment details are unavailable. Our study has the inherent limitations of a retrospective analysis, including patient selection, missing data and the potential for selection bias, where patients with elevated BMI may have been less frequently referred to or offered transplant compared to those with normal BMI. Nonetheless, it includes a large real-world cohort of MM patients who all underwent an upfront auto-HCT. We showed that an elevated BMI was not associated with an adverse impact on survival outcomes, including in patients with severe obesity. Our findings suggest that elevated BMI may not be a significant factor when it comes to determining auto-HCT eligibility for MM patients. OP and MHQ conceived and designed the study; OP and CM collected and assembled the data; OP, MHQ, SP and DRM analysed and verified the data; all authors interpreted the data, wrote and approved the article and are accountable for publication. This work was supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672). RZO, the Florence Maude Thomas Cancer Research Professor, would like to acknowledge support from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Riney Family Multiple Myeloma Research Fund at MD Anderson from the Paula and Rodger Riney Foundation. No conflicts of interest declared. The study was approved by the institutional review board at the University of Texas MD Anderson Cancer Center. The data that support the findings of this study are available on request from the corresponding author. Figure S1. Table S1. Table S2. Table S3. Table S4. Table S5. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.