Pb2102: impact of autologous stem cell trasplantation in al amyloidosis. experience in a single tertiary hospital

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: AL amyloidosis is a clonal plasma cell (PC) disorder characterized by deposition of amyloid fibrils leading to organ disfunction. Treatment must be risk-adapted. The addition of daratumumab to the first line treatment bortezomib-cyclophosphamide-dexametasone (CyBorDex) is challenging the role of autologous stem cell transplantation (ASCT), which can be deferred when hematologic complete response (hemCR) is achieved. Aims: To describe the baseline characteristics of AL amyloidosis patients undergoing ASCT. To analyze the effect of ASCT in improving hematologic responses (HR) and organ responses (OR) at day +100 and in terms of progression free survival (PFS) and overall survival (OS). To investigate factors which may predict a greater benefit for patients undergoing ASCT. Methods: An observational retrospective study was designed including patients who underwent ASCT between 1999 and 2021 at University Hospital of Salamanca. Patients were classified according to the 2012 Mayo Clinic risk stratification scale. HR were assessed according to the International Society of Amyloidosis criteria and OR according to graduate response criteria established by Muchtar et al. Results: Thirty-four patients with a median age of 53 years (40-70) were included. With a median of damaged organ of 2 (1-4) at diagnosis, renal (64.7%) and cardiac (55.9%) involvement were the most frequent. The median time from diagnosis to ASCT was 7.3 months (1.2-27.3). Induction was administered in 26 (75.6%) and 8 (23.5%) underwent directly to ASCT. Twenty-two (64.7%) received induction with proteasome inhibitor-based regimens, with CyBorDex being the most frequently used. Melphalan 200 mg/m2 was the preferred conditioning regimen (85.3%) while the rest received melphalan 140 mg/m2. At day +100 evaluation, only 30 patients had evaluable disease: 15 (50%) achieved hemCR and 6 (20%), very good partial response (VGPR). Among patients who received induction, ASCT improved HR in 10 (in 29.2% upgraded to hemCR and in 12.5% to VGPR) (Table 1) and OR in 8 (33.3%). In all patients who were in hemCR at transplant, the response was held up at day +100. High-tumor burden disease at diagnosis (>10% PC) was found in nearly half of them. Relapse was observed only in 2, at 37 and 44 months, respectively. Minimal residual diseased before ASCT was only assessed in one patient, which was negative and was maintained at +100. With a median follow-up of 71.3 months (3.3-210.1), median PFS from ASCT was 26.7 months (0.17-210.13). Patients who achieved hemCR at +100 had longer PFS (not reached vs. 23.1 months; p=0.023), and those with OR at +100 also had longer PFS (not reached vs. 6.2 months; p=0.027). Median OS from ASCT was 64.9 months (0.17-210.13). Four (13,3%) died within the first three months: 2 from septic shock and 2 from progression. Involvement of 3 o more organs significantly decreased OS (61.4 vs. 145.5 months; p=0.005). Summary/Conclusion: 1)Our series of transplant AL amyloidosis patients was carefully selected and early mortality was low. 2)Nowadays, the optimal response after ASCT is at least VGPR, which was achieved in 70% of patients at +100 days after ASCT. Among patients receiving induction, ASCT improved HR to VGPR or better in 40% and OR in 30% of them. Those in hemCR preASCT maintained the response at +100, and half of them would have undergone ASCT nowadays due to high-tumor burden at diagnosis. 3)PFS and OS results about transplantation are consistent with other series, with 46% of patients alive at 10 years and 25%, at 15 years. Factors which predict a better PFS were identified, as achieving hemCR and OR at +100. Keywords: Plasma cells, AL amyloidosis, Autologous hematopoietic stem cell transplantation