Contributions
Abstract: S411
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 12:30 - 12:45
Location: Hall A
Background
Bortezomib (B) has been reported to be very effective in AL amyloidosis with overall response rates (ORR) varying between 50-80%. However, there are no prospective data from multicenter studies on B treatment in de novo patients. We investigated the efficacy and safety of B-Dexamethasone (BD) induction treatment followed by HDM + SCT in de novo AL amyloidosis patients.
Aims
The primary aim was to improve the hematological CR rate at 6 months after SCT on intention to treat analysis from 30 to 50%. Secondary aims were OS, PFS, hematologial response rate after BD treatment, organ responses, safety and prognostic factors for survival.
Methods
Patients with biopsy proven AL amyloidosis, aged between 18-70 years, with detectable M-protein and/or level of involved FLC > 50 mg/L, WHO performance status 0-2, NYHA stage 1-2 and ejection fraction > 45% were included. Major exclusion criteria were symptomatic orthostatic hypotension, NT proBNP level > 5000 pg/ml, Troponin T> 0.06 ug/l, Bilirubin > 2x ULN, eGFR < 30 ml/min, CTCAE grade peripheral sensory neuropathy > grade 2 or > grade 1 with pain. Inclusion and exclusion criteria were installed both at entry and before stem cell mobilization (SCM). B was given subcutaneously 1.3 mg/m2 twice a week for 2 weeks in a 21-day cycle, D 20 mg orally on each B day and the following day. HDM dosage was 200 mg/m2. Hematological responses were defined according to consensus criteria with the addition of very good partial response (VGPR), defined as the difference between involved and uninvolved FLC < 40 mg/L. Cardiac, renal and liver response and progression criteria were defined according to consensus criteria with addition of NT proBNP.
Results
Median age was 59 years (range 26-70) and 60% were male. NYHA stage was 1 in 56% and 2 in 42% of patients. Mayo cardiac risk score was I (30%), II (36%), III (34%). Organ involvement was 82% renal, 66% heart, 28% liver, 14% neurological, 8% gastrointestinal and 38% of patients had 3 or more organs involved. Bone marrow plasmacells were > 10% in 28% of patients. The median FU for patients alive is 24 (10-55) months. Twelve of 50 (24%) patients could not proceed to SCM. Four patients due to B related toxicity, 3 patients did not fulfill criteria to proceed, 2 patients died (both amyloidosis related) and 3 miscellaneous. Of these 38 patients, 3 went subsequently off protocol because of ineligibility for HDM. Thirty-five out of 50 patients (70%) received HDM + SCT, one patient died of a cardiac arrest after the SCT procedure.
Conclusion
This final analysis demonstrates that the primary aim of improving CR rate at 6 months after SCT from 30 to 50% was not met. This was mainly caused by the high dropout rate before SCT. This may be due to patient selection, but we also demonstrate that BD, given twice weekly sc, despite good efficacy, cannot prevent early amyloidosis related toxicity and can induce grade 2 or higher neurotoxicity.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): AL amyloidosis, bortezomib, Autologous hematopoietic stem cell transplantation
Abstract: S411
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 12:30 - 12:45
Location: Hall A
Background
Bortezomib (B) has been reported to be very effective in AL amyloidosis with overall response rates (ORR) varying between 50-80%. However, there are no prospective data from multicenter studies on B treatment in de novo patients. We investigated the efficacy and safety of B-Dexamethasone (BD) induction treatment followed by HDM + SCT in de novo AL amyloidosis patients.
Aims
The primary aim was to improve the hematological CR rate at 6 months after SCT on intention to treat analysis from 30 to 50%. Secondary aims were OS, PFS, hematologial response rate after BD treatment, organ responses, safety and prognostic factors for survival.
Methods
Patients with biopsy proven AL amyloidosis, aged between 18-70 years, with detectable M-protein and/or level of involved FLC > 50 mg/L, WHO performance status 0-2, NYHA stage 1-2 and ejection fraction > 45% were included. Major exclusion criteria were symptomatic orthostatic hypotension, NT proBNP level > 5000 pg/ml, Troponin T> 0.06 ug/l, Bilirubin > 2x ULN, eGFR < 30 ml/min, CTCAE grade peripheral sensory neuropathy > grade 2 or > grade 1 with pain. Inclusion and exclusion criteria were installed both at entry and before stem cell mobilization (SCM). B was given subcutaneously 1.3 mg/m2 twice a week for 2 weeks in a 21-day cycle, D 20 mg orally on each B day and the following day. HDM dosage was 200 mg/m2. Hematological responses were defined according to consensus criteria with the addition of very good partial response (VGPR), defined as the difference between involved and uninvolved FLC < 40 mg/L. Cardiac, renal and liver response and progression criteria were defined according to consensus criteria with addition of NT proBNP.
Results
Median age was 59 years (range 26-70) and 60% were male. NYHA stage was 1 in 56% and 2 in 42% of patients. Mayo cardiac risk score was I (30%), II (36%), III (34%). Organ involvement was 82% renal, 66% heart, 28% liver, 14% neurological, 8% gastrointestinal and 38% of patients had 3 or more organs involved. Bone marrow plasmacells were > 10% in 28% of patients. The median FU for patients alive is 24 (10-55) months. Twelve of 50 (24%) patients could not proceed to SCM. Four patients due to B related toxicity, 3 patients did not fulfill criteria to proceed, 2 patients died (both amyloidosis related) and 3 miscellaneous. Of these 38 patients, 3 went subsequently off protocol because of ineligibility for HDM. Thirty-five out of 50 patients (70%) received HDM + SCT, one patient died of a cardiac arrest after the SCT procedure.
Conclusion
This final analysis demonstrates that the primary aim of improving CR rate at 6 months after SCT from 30 to 50% was not met. This was mainly caused by the high dropout rate before SCT. This may be due to patient selection, but we also demonstrate that BD, given twice weekly sc, despite good efficacy, cannot prevent early amyloidosis related toxicity and can induce grade 2 or higher neurotoxicity.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): AL amyloidosis, bortezomib, Autologous hematopoietic stem cell transplantation