The Clinical Features of Multiple Myeloma with AL Amyloidosis
Authors: Nashimoto Junichiro , Nomura Moe , Irita Hirofumi , Sato Kota , Miyazaki Kanji , Ogura Mizuki , Abe Yu , Tsukada Nobuhiro , Ishida Tadao , Suzuki Kenshi 
Published: November 2020

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.