Treatment of AL Amyloidosis with Two Cycles of Induction Therapy with Bortezomib and Dexamethasone Followed by Bortezomib-High Dose Melphalan Conditioning and Autologous Stem Cell Transplantation
Authors: Sanchorawala Vaishali , Shelton Anthony C , Brauneis Dina , Quillen Karen , Andrea Nancy T , Sloan John Mark , Seldin David C 
Published: October 2019

Abstract
Abstract 2019
Achievement of a hematologic complete response (CR) is a critical determinant of outcomes with respect to survival, organ response and quality of life after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. We are conducting a prospective trial to determine whether incorporating bortezomib (B) into induction therapy for 2 cycles followed by B-HDM/SCT would improve CR in newly diagnosed patients with AL. The objectives of the trial are hematologic responses, tolerability and survival. Patients receive 2 cycles of induction with B 1.3mg/m2 and dexamethasone 20mg on D1,4,8,11 every 21 days followed by conditioning regimen of B 1mg/m2 on D -6,-3,+1,+4 and HDM at 140–200mg/m2 in two divided doses on D -2 and -1 with transplantation of >2.5 × 106 autologous CD34+ cells/kg on D0. Twenty-two patients were enrolled from Jan 2010 to April 2012. The median age is 57 (range, 35–65), 15 (68%) are women, 17 (77%) have lambda isotype, 12 (55%) have multi-organ involvement, 18 (82%) have renal involvement and 11 (50%) have cardiac involvement, of which 6 (27%) have cardiac biomarker stage II and 4 (18%) stage III disease. Of 22 enrolled patients, 5 (22%) developed grade 3–4 toxicities requiring dose reductions (n=3) and discontinuation (n=2) during induction. Hematologic responses with normalization of serum free light chain concentrations occurred in 13 (59%) patients after induction treatment. Of the 22 enrolled patients, 20 proceeded with SCT, while 2 did not due to worsening of autonomic neuropathy leading to syncope and development of ESRD requiring dialysis. The median number of stem cells collected was 10.5 × 106 CD34+/kg with a mean number of stem cell collection days of 2. There was no death during induction, stem cell mobilization or collection phase. Treatment-related mortality, defined as death within 100 days of SCT, occurred in 9% (2/22) patients. Two patients developed an unusual complication of autologous graft vs host disease post SCT, which responded to administration of high-dose steroids. The median time to neutrophil and platelet engraftment after SCT was 10 and 13 days, respectively. Nineteen of 22 patients are eligible for response assessment at 6 months after SCT, as of Aug 2012. Hematologic responses were achieved by 100% of the 15 evaluable patients (67% CR and 33% VGPR) at 6 months. By intention-to-treat analysis, hematologic responses occurred in 78% (53% CR and 26% VGPR) of patients. The median survival for all 22 patients has not yet been reached. In conclusion, incorporating bortezomib into induction and conditioning yielded a high rate of hematologic response with tolerable toxicity. Two patients (9%), who were eligible for SCT at enrollment, did not proceed to SCT due to clinical deterioration during induction treatment. There was no negative impact of bortezomib induction on stem cell collection or engraftment. The unusual occurrence of two cases of graft vs host disease requires further investigation as to mechanism and potential association with this particular regimen.

Disclosures:
Sanchorawala: Millennium: The Takeda Oncology company: Research Funding. Off Label Use: Use of bortezomib in the treatment of AL amyloidosis.