P899: hovon 104; long term follow-up of autologous stem cell transplantation after bortezomib induction therapy in patients with newly diagnosed al amyloidosis

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Autologous stem cell transplantation (ASCT) is known for its excellent outcomes in a selected group of AL amyloidosis patients but few data exist on long term outcome when bortezomib induction therapy was applied before ASCT. The international HOVON 104 study enrolled 50 patients with newly diagnosed AL amyloidosis between 2012-2016. Treatment consisted of 4 cycles of bortezomib 1.3 mg/m2 s.c. on days 1,4,8,11, and dexamethasone 20 mg on days 1,2,4,5,8,9,11 and 12, in a 21-day cycle followed by high dose melphalan and ASCT.1 Here, we report the long term follow up (LTFU). Aims: The aims were to study the long-term outcome of AL amyloidosis patients treated with bortezomib induction and ASCT, with specific focus on PFS, OS, organ responses and to describe the prescribed second line treatments used at relapse. Second aim was to evaluate if the updated criteria for complete response (CR), changes the prognostic value for OS and PFS in a prospective clinical study.2 Methods: Every 3 months, data on the medical history, physical examination, NT proBNP, alkaline phosphatase, creatinine, albumin, free light chain levels, M-protein and 24 hour urine analysis were collected. From 7/50 patients, bone marrow flowcytometry samples 6 months post ASCT were available. Results: Median follow-up was 61.3 months (range 55.8 - 71.6 months). Intention to treat (ITT) analysis demonstrated a 5-year OS of 73% (95% CI 59%-84%). In total 13 patients died, with 8 additional deaths after the first publication. Two deceased patients, with a very good partial response as the best response, subsequently progressed and succumbed to multiple myeloma and plasma cell leukemia, respectively. The remaining 6 patients died due to complications related to AL amyloidosis and treatment. Five of these patients had partial response as best response achieved during protocol treatment. The 5-year ITT PFS was 52% (95% CI 38%-65%). The 5-year OS and PFS from the date of ASCT, calculated for 35 patients in total, were 91% (95% CI 76%-97%) and 68% (95% CI 50%-81%), respectively. The CR status (yes/no) before ASCT was not significantly associated with duration of OS or PFS (figure 1). Of the 7 patients with flowcytometry performed, 6 were minimal residual disease negative and 5 of those remained in CR during LTFU. After ASCT, best achieved kidney responses improved slightly from 69 to 79% (23/29 patients with renal involvement) and best cardiac responses from 78 to 91% (21/23 patients with cardiac involvement). Sixteen pts have received additional treatment with a median time to next treatment of 14 months (range 3-55). Second line treatment was very diverse and consisted of second ASCT (4 pts), lenalidomide based (6 pts), bortezomib re-treatment (4 pts), daratumumab (2 pts), oral cyclophosphamide (1 pt) and pomalidomide-dexamethasone (1 pt). Response to second line treatment was not captured. Applying the new hematological CR definition increased the CR rate slightly at all time points but did not improve the discriminatory power for PFS or OS when assessed before ASCT. Conclusion: The LTFU of the HOVON 104 study confirms the excellent outcome for patients after ASCT with a 5-year median PFS of 68% and OS of 91%. Best achieved organ response was high for both kidney and heart. Second line treatment was very diverse. Compared to other LTFU studies, such as the HOVON 41 study which demonstrated a 5-year OS of 74% after ASCT and the Boston study with an estimated 5-year OS above 80%, our results show that nowadays, with increased relapse treatment options and improved supportive care, the long term survival after ASCT can still improve.3,4References: 1Minnema MC et al, Haematologica, 2019 2Palladini G et al, Amyloid 2021, 3Hazenberg BP et al, Haematologica, 2015, 4Gupta VK et al, Biol Blood Marrow Transplant, 2019 Keywords: Bortezomib, Autologous hematopoietic stem cell transplantation, Long-term follow-up, AL amyloidosis