Safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis
- 3 years ago
Blood (2016) 128 (15): 1987–1989.
https://doi.org/10.1182/blood-2016-06-722496
In case 1, a 62-year-old white male was referred to the Mayo Clinic for consideration of autologous hematopoietic SCT for progressive hepatic and cardiac κ light chain AL. A year prior to referral, he was diagnosed with International Staging System stage III immunoglobulin G κ multiple myeloma (50% plasmacytosis; calcium, 15.3 mg/dL; β-2 microglobulin, 9.1 mg/L; creatinine, 2.1 mg/dL) with vertebral fractures. After discontinuing a trial of lenalidomide because of severe skin toxicity, he achieved a brief partial remission following 8 months of cyclophosphamide, bortezomib, and dexamethasone therapy. Prior to presenting to the clinic, he developed rapidly progressive hepatomegaly. Alkaline phosphatase was 422 U/L, and a liver biopsy demonstrated extensive amyloid deposition. Cardiac involvement was confirmed with magnetic resonance imaging with an interventricular septal thickness of 16 mm. Brain natriuretic peptide was 1483 (pg/mL), and cardiac troponin T was 0.08 (ng/mL). The patient underwent reduced-dose melphalan conditioning (100 mg/m2) and autologous stem cell rescue. SCT was uneventful; however, he did not achieve a very good partial response, and at day 100, treatment with carfilzomib, cyclophosphamide, and dexamethasone was started. After 9 months of therapy, cyclophosphamide was stopped as the light chain level plateaued after achieving very good partial response and the patient developed progressive anemia. In December 2014, he developed biochemical progression, and cyclophosphamide was added with an initial response for 6 months that was followed by rapid progression and clinical deterioration (December 2015). He developed rectal bleeding because of friable hemorrhoids and mucosal vascular involvement with amyloid. He required multiple hospitalizations for congestive heart failure and multiple surgical interventions to control rectal bleeding resulting in transfusion-dependent anemia. Daratumumab treatment was initiated as per the US prescribing information with the first dose given as an inpatient, which he tolerated well. At the conclusion of 8 weekly treatments, there was improvement in his performance status and the bleeding subsided resulting in transfusion independence. It was the first time in 4 years of illness that he achieved normalization of serum free light chains (Figure 1). NT-proBNP went from 2882 (pg/mL) to 3568 (pg/mL), and cardiac troponin T declined from 0.05 ng/mL to less than 0.01 ng/mL. Alkaline phosphatase increased mildly, but liver size remained stable.
In case 2. a 55-year-old white male was diagnosed with λ light chain amyloidosis as he presented with unexplained nephrotic syndrome with more than 10 g/d albuminuria. He was treated with 8 months of cyclophosphamide, bortezomib, and dexamethasone. At baseline, he had 15% marrow involvement by λ restricted plasma cells. He responded well to treatment (data not available), but it w
https://doi.org/10.1182/blood-2016-06-722496
In case 1, a 62-year-old white male was referred to the Mayo Clinic for consideration of autologous hematopoietic SCT for progressive hepatic and cardiac κ light chain AL. A year prior to referral, he was diagnosed with International Staging System stage III immunoglobulin G κ multiple myeloma (50% plasmacytosis; calcium, 15.3 mg/dL; β-2 microglobulin, 9.1 mg/L; creatinine, 2.1 mg/dL) with vertebral fractures. After discontinuing a trial of lenalidomide because of severe skin toxicity, he achieved a brief partial remission following 8 months of cyclophosphamide, bortezomib, and dexamethasone therapy. Prior to presenting to the clinic, he developed rapidly progressive hepatomegaly. Alkaline phosphatase was 422 U/L, and a liver biopsy demonstrated extensive amyloid deposition. Cardiac involvement was confirmed with magnetic resonance imaging with an interventricular septal thickness of 16 mm. Brain natriuretic peptide was 1483 (pg/mL), and cardiac troponin T was 0.08 (ng/mL). The patient underwent reduced-dose melphalan conditioning (100 mg/m2) and autologous stem cell rescue. SCT was uneventful; however, he did not achieve a very good partial response, and at day 100, treatment with carfilzomib, cyclophosphamide, and dexamethasone was started. After 9 months of therapy, cyclophosphamide was stopped as the light chain level plateaued after achieving very good partial response and the patient developed progressive anemia. In December 2014, he developed biochemical progression, and cyclophosphamide was added with an initial response for 6 months that was followed by rapid progression and clinical deterioration (December 2015). He developed rectal bleeding because of friable hemorrhoids and mucosal vascular involvement with amyloid. He required multiple hospitalizations for congestive heart failure and multiple surgical interventions to control rectal bleeding resulting in transfusion-dependent anemia. Daratumumab treatment was initiated as per the US prescribing information with the first dose given as an inpatient, which he tolerated well. At the conclusion of 8 weekly treatments, there was improvement in his performance status and the bleeding subsided resulting in transfusion independence. It was the first time in 4 years of illness that he achieved normalization of serum free light chains (Figure 1). NT-proBNP went from 2882 (pg/mL) to 3568 (pg/mL), and cardiac troponin T declined from 0.05 ng/mL to less than 0.01 ng/mL. Alkaline phosphatase increased mildly, but liver size remained stable.
In case 2. a 55-year-old white male was diagnosed with λ light chain amyloidosis as he presented with unexplained nephrotic syndrome with more than 10 g/d albuminuria. He was treated with 8 months of cyclophosphamide, bortezomib, and dexamethasone. At baseline, he had 15% marrow involvement by λ restricted plasma cells. He responded well to treatment (data not available), but it w