Effects of Amyloid Light-chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-center Retrospective Study

Abstract Background Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of multiple myeloma with AL amyloidosis are not particularly clear. Methods Patients with multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed. Results Compared with patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP ≧ 1000 pg/ml (P = 0.001), ALP > 187.5 IU/L (P = 0.002) and ALB < 35 g/L (P = 0.001), but lower incidence of HB < 85 g/L (P = 0.031), hypercalcemia > 2.65 mmol/L (P = 0.008), bone destruction more than three (P < 0.001), bone marrow plasma cell ratio ≧ 30% (P < 0.001) and worse D-S stage (P < 0.001). Multiple myeloma was more often complicated by λ-type AL amyloidosis than κ-type AL amyloidosis. However, further comparison found that multiple myeloma with κ-type AL amyloidosis had higher incidence of ALP > 187.5 IU/L (P = 0.001) and renal insufficiency (P = 0.001) along with worse D-S stage (P = 0.003) than multiple myeloma with λ-type AL amyloidosis. Renal biopsies of many patients suggested AL amyloidosis, but their bone marrow biopsies or subcutaneous abdominal fat pad aspirates results were negative. The existence of AL amyloidosis especially the heart involvement was related to shorter long-term survival of multiple myeloma according to univariate analysis. Cox regression model for overall survival detected the presence of AL amyloidosis in multiple myeloma having independent prognostic significance (RR = 4.52, P = 0.049). Conclusions Patients with multiple myeloma accompanied by AL amyloidosis have milder target organ damage and lower tumor burden. The incidence of AL amyloidosis in κ-type multiple myeloma is lower but more severe than λ-type multiple myeloma. Renal biopsy can help to identify patients with AL amyloidosis. AL amyloidosis is an independent poor prognostic factor for multiple myeloma is mainly because involvements of important organs especially the heart.

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Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study

Cancer Management and Research ◽

10.2147/cmar.s287922 ◽

2021 ◽

Vol Volume 13 ◽

pp. 1343-1356

Author(s):

Junhui Xu ◽

Mangju Wang ◽

Ye Shen ◽

Miao Yan ◽

Weiwei Xie ◽

...

Keyword(s):

Multiple Myeloma ◽

Retrospective Study ◽

Light Chain ◽

Clinical Characteristics ◽

Single Center ◽

Light Chain Amyloidosis ◽

Amyloid Light Chain

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Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study

10.21203/rs.3.rs-88885/v1 ◽

2020 ◽

Author(s):

Junhui Xu ◽

Mangju Wang ◽

Ye Shen ◽

Miao Yan ◽

Weiwei Xie ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Light Chain ◽

Clinical Characteristics ◽

Cox Regression ◽

Prognostic Significance ◽

Al Amyloidosis ◽

Smoldering Multiple Myeloma ◽

Independent Prognostic Significance ◽

Amyloid Light Chain

Abstract Background: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis is not particularly clear.Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information were collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationships between the clinical parameters and survival were also assessed.Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/ml (P<0.001), ALP>187.5IU/L (P=0.032) and ALB<25g/L (P<0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/ml (P=0.030) and Alb<25g/L (P=0.024). The existence of AL amyloidosis especially the heart involvement was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/ml in symptomatic multiple myeloma having independent prognostic significance (RR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P<0.001).Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent prognostic significance (RR=8.741, P=0.002).Conclusions: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma is mainly because involvements of important organs especially the heart. AL amyloidosis probablely has a greater impact on the prognosis of smoldering multiple myeloma than symptomatic multiple myeloma.

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Prevalence and clinical implications of t(11;14) in patients with amyloid light-chain amyloidosis with or without concurrent multiple myeloma

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyy202 ◽

2019 ◽

Vol 49 (2) ◽

pp. 195-198 ◽

Cited By ~ 2

Author(s):

Hiroki Kobayashi ◽

Yoshiaki Abe ◽

Daisuke Miura ◽

Kentaro Narita ◽

Akihiro Kitadate ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Clinical Implications ◽

Light Chain Amyloidosis ◽

Amyloid Light Chain

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The Occurrence of AL Amyloidosis (Light-Chain Amyloidosis) in Patients with Multiple Myeloma in Lower Silesia Region, Poland

Advances in Clinical and Experimental Medicine ◽

10.17219/acem/37068 ◽

2014 ◽

Vol 23 (2) ◽

pp. 235-244

Author(s):

Lidia Usnarska-Zubkiewicz ◽

Jadwiga Hołojda ◽

Michał Jeleń ◽

Anna Zubkiewicz-Zarębska ◽

Jakub Dębski ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Al Amyloidosis ◽

Light Chain Amyloidosis ◽

Lower Silesia

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Patterns of Treatment Failure in Systemic Light Chain Amyloidosis with Long-Term Survival after Chemotherapy

Blood ◽

10.1182/blood.v128.22.2132.2132 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2132-2132

Author(s):

Hee Kyung Kim ◽

Kihyun Kim ◽

Lee Hansang ◽

Heo Mi Hwa ◽

Park Silvia

Keyword(s):

Treatment Failure ◽

Light Chain ◽

Cardiac Response ◽

Al Amyloidosis ◽

Term Survival ◽

Long Term Survival ◽

Light Chain Amyloidosis ◽

Hematologic Response

Abstract Background The prognosis of systemic light chain (AL) amyloidosis is poor, which is associated early death assiated with cardiac involvement. It was reported that patients who avoided earth death have better survival than myeloma patients. However, the patterns of treatment failure of AL amyloidosis patients with long-term survival have not been evaluated. The aim of this study was to analyze the clinical outcome of patients with AL amyloidosis who survived more than 1 year and experienced treatment failure after systemic chemotherapy. Methods In this retrospective cohort study, 165 patients with AL amyloidosis received chemotherapy including ASCT in Samsung medical center between September 1997 and September 2015 were analyzed. The conditioning chemotherapy of ASCT was high-dose melphalan (200mg/m2). The patients who survived more than 1 year and showed disease progression or death were included in the study population. Progression was defined as first hematologic or organ progression after diagnosis of systemic amyloidosis. Hematologic or organ progression was evaluated according to the Roundtable on Clinical Research in Immunoglobulin Light-chain Amyloidosis. The progression-free survival and overall survival were analyzed. Results A total of 112 patients who survived more than 1 year during the study period with median follow-up 50.3 months, 7 patients was lost to follow-up and 47 patients did not showed progression. 58 patients experienced death or progression and they were eligible for analysis. 14 of 58 (24.1%) patients received ASCT, 13 (22.4%) patients received bortezomib-based regimens, 6 (10.3%) patients received oral melphalan with dexamethasone before progression. 4 (6.9%) patients achieved hematologic complete remission (CR) and 5 (8.6%) patients achieved hematologic very good partial response (VGPR), all of 9 patients demonstrated cardiac progresion. Otherwise, 27 of 47 patients (57.4%) without progression achieved hematologic CR or VGPR. Among 54 patients who did not achieve hematologic CR, 24 (44.4 %) patients showed hematologic progression and 28 (51.9%) patients showed cardiac progression, kidney progression was 17 (31.5%) and liver progression was 3 (5.6%), respectively. There were 4 patients with hematologic progression followed by cardiac progression, and the median time interval from hematologic progression to cardiac progression was 2.6 months. 39 deaths (67.2%) were identified in cohort and most common cause of death was cardiac progression (12 of 39 deaths - heart failure, fatal arrhythmia, cardiac arrest). Conclusion More than half of patients in this cohort received ASCT or bortezomib based chemotherapy, cardiac progression was a leading cause of treatment failure in systemic AL amyloidosis with long-term survival (>1 year), even in the patients with hematologic CR. Continuation of chemotherapy or ASCT beyond hematologic response might be needed to achieve cardiac response and long-term survival in patients with AL amyloidosis who demonstrated cardiac progression. Further studies to elucidate the efficacy of chemotherapy beyond hematologic response are warranted. Disclosures No relevant conflicts of interest to declare.

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Near tetrapoloid karyotype with translocation t(11;14) in a Moroccan patient with amyloid light-chain amyloidosis and multiple myeloma

Leukemia Research Reports ◽

10.1016/j.lrr.2020.100217 ◽

2020 ◽

Vol 14 ◽

pp. 100217

Author(s):

Hasna Hamdaoui ◽

Abdelhafid Natiq ◽

Oumaima Benlarroubia ◽

Thomas Liehr ◽

Hind Dehbi ◽

...

Keyword(s):

Multiple Myeloma ◽

Light Chain ◽

Light Chain Amyloidosis ◽

Amyloid Light Chain ◽

Moroccan Patient

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Daratumumab, pomalidomide, and dexamethasone as a bridging therapy to autologous stem cell transplantation in a case of systemic light-chain amyloidosis with advanced cardiac involvement

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218815305 ◽

2018 ◽

Vol 25 (4) ◽

pp. 1021-1025 ◽

Cited By ~ 3

Author(s):

Justin R Arnall ◽

Saad Z Usmani ◽

Hawawu Adamu ◽

Joseph Mishkin ◽

Manisha Bhutani

Keyword(s):

Multiple Myeloma ◽

Abdominal Pain ◽

Light Chain ◽

Cardiac Involvement ◽

Single Agent ◽

Al Amyloidosis ◽

Light Chain Amyloidosis ◽

Hematologic Disorder ◽

Complete Hematologic Response ◽

Paradoxical Worsening

Systemic light-chain (AL) amyloidosis is a rare hematologic disorder where proteins infiltrate tissues leading to organ failure and death. Cardiac involvement, present in ∼70% of patients, determines stage and prognosis of the disease, with advanced involvement having a median survival of six months. The treatment of light-chain amyloidosis is directed at recovering organ function with therapeutic strategies following those of multiple myeloma with plasma cell-directed therapies. The use of single agent daratumumab has been reported in light-chain amyloidosis achieving rapid and deep responses. The combination of daratumumab, pomalidomide, and dexamethasone (DaraPomD) is particularly interesting for severe AL based on success in multiple myeloma. A 43-year-old female with light-chain amyloidosis and concomitant multiple myeloma presented with severe bowel dysmotility causing abdominal pain, anemia, and a 100-pound unintentional weight loss. A combination of cyclophosphamide, bortezomib, and dexamethasone was initiated but after five cycles her symptoms were progressing and therapy was switched to DaraPomD to optimize response. At the conclusion of two cycles she had achieved an amyloid complete-hematologic response, with her recurring ileus and abdominal pain significantly improved. Additionally, cardiac markers also suggested a rapid response without a common paradoxical worsening of congestive heart failure, and was overall well tolerated. Given the severe symptoms and refractory nature of our patient's disease DaraPomD was reasonable. With the tolerability and response seen, this patient experience supports a formal clinical trial evaluating the safety and efficacy of DaraPomD in light-chain amyloidosis.

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Tumor cells in light-chain amyloidosis and myeloma show different transcriptional rewiring of normal plasma cell development

Blood ◽

10.1182/blood.2020009754 ◽

2021 ◽

Author(s):

Daniel Alameda ◽

Ibai Goicoechea ◽

Marco Vicari ◽

Elena Arriazu ◽

Alice Nevone ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Light Chain ◽

Clinical Presentation ◽

Light Chain Amyloidosis ◽

New Born ◽

Transcriptional Rewiring ◽

Differentiation Stage ◽

Secondary Lymphoid Organs

Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, but there are no studies investigating the differentiation stage of tumor PCs in patients with AL and MM. We sought to define a transcriptional atlas of normal PC development (n=11) in secondary lymphoid organs (SLO), peripheral blood (PB) and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL (n=37), MM (n=46) and MGUS (n=6). Based on bulk and single-cell RNAseq, we observed thirteen TPs during transition of normal PCs throughout SLO, PB and BM; that CD39 outperforms CD19 to discriminate new-born from long-lived BM-PCs; that tumor PCs expressed the most advantageous TPs of normal PC differentiation; that AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and new-born BM-PCs; that AL and MM patients enriched in immature TPs had inferior survival; and that TPs related with protein N-linked glycosylation are upregulated in AL. Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies.

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