Outcomes in Patients on Hemodialysis Who Undergo High Dose Therapy Followed By Autologous Peripheral Blood Stem Cell Transplant for Multiple Myeloma in the Era of Novel Agents
Authors: Ye J. Christine , Nandagopal Lakshminarayanan , Ventimiglia Marie , Abidi Muneer H. , Ayash Lois , Lum Lawrence G , Uberti Joseph P. , Ratanatharathorn Voravit , Zonder Jeffrey , Bhutani Divaya , Deol Abhinav 
Published: November 2019

Abstract
About 5% of patients with Multiple Myeloma (MM) have evidence of severe renal dysfunction requiring hemodialysis (HD) at the time of diagnosis. Often, patients on HD are not referred for autologous stem cell transplant (ASCT) due to the concern of higher treatment-related mortality. There is a dearth of data regarding outcomes in patients on HD who undergo ASCT in the era of novel agents.
We conducted a retrospective chart review of fifteen patients on HD who underwent their first ASCT at our institution from June 2005 to December 2013. The patient characteristics are shown in Table 1. All patients had novel drugs for induction therapy prior to ASCT; thirteen patients had received 3 drug regimens and 2 patients had received 2 drug regimens. Eight patients received regimens containing both Lenalidomide and Bortezomib, five received Bortezomib-based regimens and one received Lenalidomide-based regimens. Three patients received more than one regimen. The median time from diagnosis to ASCT was 9.9 months (range, 4.7-33.1). Median patient follow-up was 18 months (range, 0.2-82 months). One patient died 7 days after transplant due to sepsis resulting in multi-organ failure. All patients received Melphalan in the inpatient unit. All patients received G-CSF 5µg/Kg from day + 6 till ANC 1500/ µL. Norfloxacin, acyclovir and fluconazole were used for antimicrobial prophylaxis during hospitalization.
Two patients (13%) were able to stop dialysis after ASCT. The disease status of all patients at day 100 is shown in Table 2. At the day 100 assessment of 14 evaluable patients, five had an upgrade in the disease response and nine had no change. Seven patients received maintenance therapy after ASCT with Lenalidomide (6) and Bortezomib (1). Figures 1 and 2 display the Kaplan-Meier curves for overall survival (OS) and relapse free survival (RFS). The median OS of these patients at 5 years was 59% and RFS was 37 months.
Our experience in HD patients who underwent ASCT for MM with the use of novel agents during induction suggests that ASCT is safe with acceptable toxicity and a median RFS is about 3 years. The relapse-free survival could be improved with the use of novel agents for maintenance therapy in more patients. The application of novel agents during induction and maintenance therapies may be responsible for improving outcomes in these patients.
Table 1: Patient Characteristics Patient Characteristics N (%) Median Age (range) 51 (31-67) Gender Male 11 (73%) Females 4 (27%) Race Caucasians 8 (53%) Others 7 (47%) Disease status at time of ASCT SD 1 (7%) PR 7 (47%) VGPR 4 (27%) CR 3 (19%) Median creatinine clearance (range) 9 (3-43) Subtype IgG Kappa 7 (47%) IgG Lambda 3 (19%) Kappa Light Chain 2 (13.5%) Lambda Light Chain 2 (13.5%) Non- Secretory 1 (7%) Cytogenetic Risk Standard 11 (73%) High Risk 2 (13.5%) Unknown 2 (13.5%) Median Melphalan Dose mg/m2 (range) 140 (100-140) (One patient received 100 mg/m2) Median CD 34 Cell dose x106/kg (range) 3.34 (2.31-4.96) Median Engraftment Day (range) WBC 13 (11-14) Platelets 24 (17-89) Median Days of Hospitalization (range) 20 (9-34)
SD: stable disease; PR: partial response; VGPR: very good partial response; CR: complete response
Table 2: Disease status at Day 100 post ASCT Disease Status PR 3 (19%) VGPR 10 (67%) CR 1 (7%) Not available 1 (7%)
Figure 1 Figure 1.
Figure 2 Figure 2.

Disclosures
No relevant conflicts of interest to declare.