Cardiac Magnetic Resonance–Derived Extracellular Volume Mapping for the Quantification of Hepatic and Splenic Amyloid

Background: Systemic amyloidosis is characterized by amyloid deposition that can involve virtually any organ. Splenic and hepatic amyloidosis occurs in certain types, in some patients but not others, and may influence prognosis and treatment. SAP (serum amyloid P component) scintigraphy is uniquely able to identify and quantify amyloid in the liver and spleen, thus informing clinical management, but it is only available in 2 centers globally. The aims of this study were to examine the potential for extracellular volume (ECV) mapping performed during routine cardiac magnetic resonance to: (1) detect amyloid in the liver and spleen and (2) estimate amyloid load in these sites using SAP scintigraphy as the reference standard. Methods: Five hundred thirty-three patients referred to the National Amyloidosis Centre, London, between 2015 and 2017 with suspected systemic amyloidosis who underwent SAP scintigraphy and cardiac magnetic resonance with T1 mapping were studied. Results: The diagnostic performance of ECV to detect splenic and hepatic amyloidosis was high for both organs (liver: area under the curve, −0.917 [95% CI, 0.880–0.954]; liver ECV cutoff, 0.395; sensitivity, 90.7%; specificity, 77.7%; P <0.001; spleen: area under the curve, −0.944 [95% CI, 0.925–0.964]; spleen ECV cutoff, 0.385; sensitivity, 93.6%; specificity, 87.5%; P <0.001). There was good correlation between liver and spleen ECV and amyloid load assessed by SAP scintigraphy (r=0.504, P <0.001; r=0.693, P <0.001, respectively). There was high interobserver agreement for both the liver and spleen (ECV liver intraclass correlation coefficient, 0.991 [95% CI, 0.984–0.995]; P <0.001; ECV spleen intraclass correlation coefficient, 0.995 [95% CI, 0.991–0.997]; P <0.001) with little bias across a wide range of ECV values. Conclusions: Our study demonstrates that ECV measurements obtained during routine cardiac magnetic resonance scans in patients with suspected amyloidosis can identify and measure the magnitude of amyloid infiltration in the liver and spleen, providing important clues to amyloid type and offering a noninvasive measure of visceral amyloid burden that can help guide and track treatment.

The Clinical Features of Multiple Myeloma with AL Amyloidosis

Background Multiple myeloma and AL amyloidosis are both caused by the clonal proliferation of the abnormal plasma cells. Although, the difference of the genetic features of multiple myeloma and AL amyloidosis has been reported, we see some patients present with both cases. We retrospectively investigated the clinical features of patients diagnosed with multiple myeloma and AL amyloidosis. Methods We reviewed medical records of patients who were diagnosed with multiple myeloma and AL amyloidosis before initiating treatment during January 2009 to November 2019 in our institution. We excluded patients who did not reach 10% of the plasma cells in the bone marrow. Patients diagnosed with light chain deposition disease were excluded. Treatment regimens were at the discretion of the treating physician. Results Forty-two patients were diagnosed with multiple myeloma and AL amyloidosis. The median follow-up time since diagnosis was 20 months [0-89]. The median age was 63-year-old [43-85]. There was no difference between the sex (male: female=1:1). Twenty-nine (69.0%) patients had lambda type of light chain. Patients with ISS stage I, II, and III were 13(31.7%), 21(51.2%), and 7(17.1%). Patients with R-ISS stage I, II, and III were 4(10.3%), 30(76.9%), and 5(12.8%). Patients with Revised Mayo Clinic AL amyloidosis Staging System 1, 2, 3, and 4 were 3(10.0%), 4(13.3%), 8(26.7%), and 15(50.0%). Twelve (35.3%), 2 (6.9%), 1 (3.4%) and 1 (4.0%) patients had t(11;14), t(4;14), t(14;16) and del(17p) by FISH analysis, respectively. Fourteen (33.3%), 16(38.1%), and 8(19.0%) patients were diagnosed with cardiac, renal, and hepatic amyloidosis, respectively. Thirty-five (83.3%) patients received Bortezomib containing regimen for the initial treatment (e.g., Bortezomib+Dexamethasone(7.1%), Cyclophosphamide+Bortezomib+Dexamethasone(23.8%), Bortezomib+Melphalan+Dexamethasone(7.1%), Bortezomib+Melphalan+Prednisolone(9.5%), Bortezomib+Lenalidomide+Dexamethasone(35.7%)). Thirteen (31.0%) patients underwent autologous stem cell transplantation with high dose melphalan. Median PFS was 25 months and the median OS was 82 months. There were no significant differences in OS between the I-SSS, R-ISSS, and Revised Mayo Clinic AL amyloidosis Staging System groups. Patients diagnosed with cardiac or hepatic amyloidosis had significantly worse outcome. The median OS diagnosed with and without cardiac amyloidosis were 14 and 28 months (p value = 0.034), and the median OS diagnosed with and without hepatic amyloidosis were 8 and 24 months (p value = 0.012). Conclusion Multiple myeloma with AL amyloidosis, especially cardiac or hepatic amyloidosis, has a poor prognosis even if treated with novel agents. Searching for the optimal treatment for these patient groups remains to be an issue. Disclosures Nashimoto: Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Ishida:Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Speakers Bureau. Suzuki:Bristol-Myers Squibb, Celgene and Amgen: Research Funding; Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria.