Once Weekly Subcutaneous Bortezomib, Cyclophosphamide, and Dexamethasone As Induction Therapy for All AL Amyloidosis
Authors: Abbas Hashim , Rybicki Lisa A. , Reu Frederic J. , Samaras Christy , Smith Mitchell R. , Hastings Debbie , Valent Jason 
Published: October 2019

Abstract
High dose melphalan followed by autologous stem cell transplant is the standard of care for all transplant eligible AL amyloidosis patients. Due to medical insurance approvals and pre-transplant evaluation, treatment is delayed by months. Given that there are many patients who respond quickly to bortezomib based regimens, we have adopted a bortezomib based induction regimen in an attempt to prevent early progression or death due to amyloidosis.
Materials and methods:
All AL amyloidosis patients treated at the Cleveland Clinic who received bortezomib 1.3 mg/m2 subcutaneous, cyclophosphamide 300mg/m2 (dose cap at 500 mg) intravenous or oral, and dexamethasone 20 mg intravenous or oral (CyBorD) on day 1,8, and15, of a 28 day cycle were included in this analysis. Patient information was obtained from an institutional review board approved database and electronic medical record review. Hematologic response was assessed every 28 days. Transplant eligible patients who achieved early complete hematologic response (CR) completed up to 6 cycles of CyBorD followed by high dose melphalan and autologous stem cell transplant (ASCT). If there was no CR at the end of 2 cycles of therapy, patients underwent high dose melphalan and ASCT. Non- transplant eligible patients completed a planned 6 cycles of CyBorD. The primary outcome of the study was to assess overall survival (OS) of all AL amyloidosis patients by Kaplan-Meier estimate. The secondary outcomes were to assess the best hematologic response1, with CyBorD plus ASCT versus CyBorD alone and evaluate if any transplant eligible patients were unable to proceed to ASCT after receiving CyBorD.
Results:
With a median follow up of 30 months, patients who received CyBorD plus ASCT had a 92% probability of survival. Patients who received CyBorD alone had a 47 % probability of survival. All patients who were deemed transplant eligible at diagnosis underwent high dose melphalan and ASCT. The median NT-proBNP for patients who underwent ASCT was 305 pg/ml and for patients who were transplant ineligible was 6047 pg/ml. The best hematologic response in patients who received bortezomib based induction plus transplant was CR 71%, very good partial response (VGPR) 18%, stable disease (SD) 6%, and progressive disease (PD) 6%. Patients treated with CyBorD alone had a CR 56%, VGPR 6%, SD 19%, and PD 12%.
Discussion:
None of the transplant eligible patients were deemed transplant ineligible after the induction therapy. The OS was excellent for patients who underwent transplant. The percentage of CR in the transplant eligible patients compared favourably to historical reports of CR with ASCT alone. Only 12 % of patients undergoing ASCT failed to achieve a VGPR compared to 37% of patients with CyBorD alone. Certainly the transplant ineligible patients had severely compromised baseline cardiac function but despite that the probability of survival at 30 months was 47%. With this data, we plan to standardize bortezomib based induction AL amyloidosis treatment with a care path for the entire Cleveland Clinic health care system.
Abbreviations: NT-proBNP (amino-terminal pro-B-type natriuretic peptide).
References:
1. Palladini G, Dispenzieri A, Gertz MA, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9
Figure 1 Probability of survival for all AL amyloidosis patients treated with CyBorD. Figure 1. Probability of survival for all AL amyloidosis patients treated with CyBorD.

Disclosures
Reu: Takeda: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Celgene: Research Funding. Smith:Genentech: Honoraria; Abbvie: Research Funding; Spectrum: Honoraria; Celgene: Honoraria. Valent:Takeda: Speakers Bureau; Celgene: Speakers Bureau.