Comparing Outcomes of Outpatient Vs. Inpatient High-Dose Melphalan Based Conditioning Regimens Followed By Autologous Hematopoietic Cell Transplantation in Myeloma

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy and high-dose melphalan followed by autologous hematopoietic cell transplantation (HCT) plays a pivotal role in consolidation of response after initial anti-myeloma therapy. High-dose therapy has been historically applied in the inpatient setting, but some centers have shifted autologous HCT to outpatient setting due to various reasons including health care cost. Here, we compared the survival outcomes of high-dose melphalan followed by autologous HCT at a tertiary referral transplant center since its inception of formal outpatient HCT program.

Methods: Clinical transplant data on MM patients who underwent high-dose melphalan at Moffitt Cancer Center (MCC) between 2013 and 2021 were retrospectively reviewed. BMT Research Analysis Information Network (BRAIN) database was used for querying the data. The study population consists of those MM patient who received their first autologous HCT with high-dose melphalan based conditioning regimens. HCT outcomes were compared based on the location of transplant (inpatient vs. outpatient) with the outpatient BMT program officially launching in 2013. Autologous HCT was prescribed as an outpatient by default unless there were reasons such as renal failure requiring dialysis, cardiovascular complications requiring inpatient monitoring, psychosocial concerns, patient refusal for outpatient, or physician discretion. HCT for amyloidosis was excluded from this study. Outpatient HCT team consists of a dedicated transplant faculty member and an advanced practice professional who make daily round on outpatient HCT. Patients are seen in the outpatient BMT treatment center during the day and the arrangements have been made to directly admit to inpatient BMT unit when clinical indications arise. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier method and compared with log-rank testing. Cumulative incidence function was compared with Gray's test.

Results: There were 1349 MM patients who underwent autologous HCT with high-dose melphalan-based regimen at MCC from 2013 to 2021. There were 670 patients in the inpatient group and 679 in the outpatient. The number of autologous HCT performed in the outpatient setting has increased overtime and surpassed the inpatient in 2018 with 74.6% of HCT performed as outpatient in 2021. Median age for both groups were 63 years and the median KPS of 90. Median HCT-CI was 3 for both groups. Median serum creatinine was 0.9 (range, 0.4-11.9) for inpatient, and 0.8 (range, 0.4-3.8) for outpatient. Within 30 days from HCT, 57.1% of outpatient MM HCT recipients were admitted to the hospital. Median length of stay for inpatient group was 14 days.

Univariate analysis showed that the 5-year OS for outpatient vs. inpatient HCT was 80.6% (95% confidence interval (CI): 76.0-84.3) and 71.0% (95%CI: 66.6-74.8), respectively (Log rank, p=0.0009, Figure). The 5-year PFS for outpatient vs. inpatient HCT was 58.0% (95%CI: 52.6-63.0) and 50.7% (95%CI: 46.2-55.1), respectively (Log rank, p=0.012). The 5-year cumulative incidence of relapse for outpatient vs. inpatient HCT was 34.6% (95%CI: 29.7-39.5) and 39.8% (95%CI: 35.6-44.1), respectively (Gray's test, p=0.046). The 5-year cumulative incidence of nonrelapse mortality (NRM) for outpatient vs. inpatient was 7.3% (95%CI: 4.9-10.3) and 9.3% (95%CI: 6.9-12.1), respectively (Gray's test, p=0.25). Additional multivariate analysis will be provided at the presentation.

Conclusions: Since the inception, the volume of outpatient HCT has steadily increased at our institution. In our retrospective analysis, outpatient MM HCT patients had better OS, PFS, with decreased risk of MM relapse compared to inpatient group. However, NRM was similar between the group. These survival differences may be due to patient selection and early period for inpatient HCT. Outpatient HCT is safe and appropriate transplant modality in the majority of MM patients who are candidate for such intervention. Further analysis to evaluate disease related prognostic factors is planned.

Hansen:BMS IMW Ide-Cel Academic Advisory Board: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Survivorship: Honoraria. Liu:Sanofi: Speakers Bureau. Freeman:Sanofi: Honoraria; Janssen: Honoraria, Research Funding; Amgen: Honoraria; Incyte: Honoraria; Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Blue:Oncopeptides: Honoraria; Sanofi: Consultancy, Speakers Bureau; Jassen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Grajales-Cruz:sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Baz:Pfizer: Membership on an entity's Board of Directors or advisory committees; Shattuck labs: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; karyopharm: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; genentech: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Sanofi: Consultancy, Honoraria; celgene: Consultancy, Honoraria; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shain:AbbVie: Research Funding; Amgen: Speakers Bureau; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Karyopharm: Research Funding, Speakers Bureau. Locke:Imedex: Other: Education or editorial role; GammaDelta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Research Funding; Umoja: Membership on an entity's Board of Directors or advisory committees; EcoR1: Consultancy; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Society for Immunotherapy of Cancer: Other: Education or editorial role; A2: Membership on an entity's Board of Directors or advisory committees; ASH: Other: Education or editorial role; Aptitude Health: Other: Education or editorial role; BioPharma Communications CARE Education: Other: Education or editorial role; Gerson Lehrman Group: Consultancy; National Cancer Institute: Research Funding; Leukemia and Lymphoma Society: Research Funding; Cowen: Consultancy; BlueBird Bio: Research Funding; Clinical Care Options Oncology: Other: Education or editorial role; Cellular Biomedicine Group: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Wugen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Iovance: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Calibr: Membership on an entity's Board of Directors or advisory committees; Moffitt Cancer Center: Patents & Royalties: several patents held by the institution in his name (unlicensed) in the field of cellular immunotherapy; Emerging Therapy Solutions: Consultancy; BMS: Research Funding; Novartis: Research Funding; Allogene: Research Funding; Allogene: Membership on an entity's Board of Directors or advisory committees; Sana: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees. Alsina:BMS, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding.