Light chain multiple myeloma with cutaneous AL amyloidosis

2008 ◽  
Vol 6 (9) ◽  
pp. 744-745 ◽  
Author(s):  
Maria Rita Becker ◽  
Rainer Rompel ◽  
Jörg Plum ◽  
Timo Gaiser
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Al Amyloidosis

A pharmacist’s review of the treatment of systemic light chain amyloidosis

2020 ◽  
pp. 107815522096353
Author(s):  
David M. Hughes ◽  
Andrew Staron ◽  
Vaishali Sanchorawala
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Case Reports ◽  
Evidence Base ◽  
Chemotherapeutic Agents ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Al Amyloidosis ◽  
Tertiary Referral Center ◽  
Treatment Considerations

Objective Systemic light-chain (AL) amyloidosis is an uncommon hematologic plasma cell dyscrasia that is becoming increasingly recognized. Therapeutic agents used in AL amyloidosis overlap with those used in multiple myeloma; however, differences in disease features change treatment efficacy and tolerance. Pharmacists must be cognizant of these distinctions. Herein, this review article provides an up-to-date guide to treatment considerations for systemic AL amyloidosis in both the front-line and relapsed settings. Data sources: A comprehensive literature search was performed using the PubMed/Medline database for articles published through (June 2020) regarding treatments for AL amyloidosis. Search criteria included therapies that are FDA approved for multiple myeloma, as well as investigational agents. This review of chemotherapeutic agents reflects the current clinical practice guidelines endorsed by NCCN along with commentary based on the experience of pharmacists from a tertiary-referral center treating many patients with AL amyloidosis. Data consists of randomized controlled trials, observational cohorts, case reports, and ongoing clinical trials. Data summary: Frontline options discussed here include high-dose melphalan with autologous stem cell transplantation and bortezomib-based regimens. Regarding the relapsed setting, supporting data are compiled and summarized for: bortezomib, ixazomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, elotuzumab, isatuximab, venetoclax, NEOD001, and melflufen. Conclusions The treatment platform for AL amyloidosis is expanding with novel agents traditionally used in multiple myeloma being adopted and modified for use in AL amyloidosis. The pharmacist’s familiarity with the clinical evidence base for these agents and how they fit into standard protocols for AL amyloidosis is critical as dosing and monitoring recommendations are unique from multiple myeloma.

scholarly journals Confocal Cornea Microscopy Detects Involvement of Corneal Nerve Fibers in a Patient with Light-Chain Amyloid Neuropathy Caused by Multiple Myeloma: A Case Report

2016 ◽  
Vol 8 (2) ◽  
pp. 134-139 ◽  
Author(s):  
Dietrich Sturm ◽  
Tobias Schmidt-Wilcke ◽  
Tineke Greiner ◽  
Christoph Maier ◽  
Marc Schargus ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Light Chain ◽  
Nerve Fibers ◽  
Al Amyloidosis ◽  
Fiber Damage ◽  
Small Fiber ◽  
Corneal Nerve ◽  
Al Amyloid

Changes in the subbasal corneal plexus detected by confocal cornea microscopy (CCM) have been described for various types of neuropathy. An involvement of these nerves within light-chain (AL) amyloid neuropathy (a rare cause of polyneuropathy) has never been shown. Here, we report on a case of a patient suffering from neuropathy caused by AL amyloidosis and underlying multiple myeloma. Small-fiber damage was detected by CCM.

scholarly journals Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172996 ◽  
Author(s):  
Surbhi Sidana ◽  
Mayur Narkhede ◽  
Paul Elson ◽  
Debbie Hastings ◽  
Beth Faiman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Al Amyloidosis

Utility of Multiparameter Flow Cytometry Immunophenotypic Studies In Patients with Systemic Light Chain (AL) Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4051-4051
Author(s):  
Bruno Paiva ◽  
María-Belén Vidriales ◽  
Jose J. Perez ◽  
Maria-Consuelo López-Berges ◽  
Ramón García-Sanz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Differential Diagnosis ◽  
Plasma Cell ◽  
Light Chain ◽  
Cell Cycle Analysis ◽  
Disease Assessment ◽  
Multiparameter Flow Cytometry ◽  
Al Amyloidosis

Abstract Abstract 4051 Multiparameter flow cytometry (MFC) immunophenotyping has shown to be of value for differential diagnosis and minimal residual disease assessment in multiple myeloma. However, the clinical value of MFC immunophenotyping in other plasma cell disorders (PCD) remains largely unexplored. Systemic light chain (AL) amyloidosis is a rare PCD characterized by the accumulation of monoclonal light chain fragments leading to end-organ damage and short survival. Bone marrow (BM) plasma cell (PC) infiltration in AL is usually low and thus the identification of clonal PC can be often difficult by immunohistochemistry and/or immunofluorescence. In the present study we focused on 34 BM samples sent to our institution with a suspected diagnosis of AL. MFC immunophenotypic studies were performed using the following 4-color combinations of MoAbs (FITC/PE/PerCP-Cy5.5/APC): CD38/CD56/CD19/CD45 (n=34); in addition cy-Kappa/cy-Lambda/CD19/CD38 staining was add to confirm the clonal or polyclonal nature of BMPC in equivocal cases. Ploidy and cell cycle analysis were additionally performed in a subset of cases (n=12/34). From the total 34 cases included in the present study, 28 had a confirmed diagnosis of AL. The remaining 6 cases were finally diagnosed with localized - amyloidoma - (n=2) and familial (n=1) forms of amyloidosis, multiple myeloma-associated amyloid (n=2) and congestive pericarditis (n=1). Interestingly, the presence of clonal PC was detected by MFC in 27 of the 28 (96%) patients with AL; in turn, clonal PC were undetectable in the BM of all cases with localized and familial forms of amyloidosis. The median overall level of PC (M-PC plus N-PC) seen in MFC immunophenotypic analyses of BM samples of the 28 patients with AL was 1.9% (range: 0.1% - 15%), with a significant positive correlation between PC enumerated by MFC and conventional morphology (r=0.5; p=.01). Within the BMPC compartment, the median proportion of clonal PC was of 94% (mean 81% ± 29%); in 6 cases all BMPC were clonal while in the remaining 22 patients residual normal PC persisted (median of normal PC/BMPC 13% ± 31%). The most common aberrant phenotypes were down-regulation of CD19 (92%) and CD45 (83%), followed by overexpression of CD56 (56%) and infra-expression of CD38 (42%). Aneuploidy was only found in 18% of cases, all of them hyperdiploid. Cell cycle analysis showed a median % of S-phase and G2-Mitosis PC of 0.7% and 3.5%, respectively. Concerning patients' outcome, cases with undetectable normal PC (6/28, 21%) had a significantly decreased overall survival (OS) compared to patients with persistent BM normal PC at diagnosis (22/28, 79%) with 3-year OS rates of 0% vs. 59%, respectively (p=.001). In summary, these preliminary data suggests that MFC immunophenotyping investigations may be clinically relevant in patients with suspected amyloidosis for i) differential diagnosis between AL and other forms of amyloidosis and, ii) prognostication of patients with AL according to the presence or absence of baseline persistent normal PC. Disclosures: No relevant conflicts of interest to declare.

Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5036-5036 ◽  
Author(s):  
Beihui Huang ◽  
Juan Li ◽  
Junru Liu ◽  
Dong Zheng ◽  
Mei Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Side Effects ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Hematologic Response ◽  
Best Response ◽  
Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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

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

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

2018 ◽  
Vol 25 (4) ◽  
pp. 1021-1025 ◽  
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.

scholarly journals The Clinical Features of Multiple Myeloma with AL Amyloidosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Junichiro Nashimoto ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Kota Sato ◽  
Kanji Miyazaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Features ◽  
Light Chain ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Staging System ◽  
Stage I ◽  
P Value ◽  
Al Amyloidosis ◽  
Hepatic 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.

scholarly journals Treatment with Daratumumab in Patients with Multiple Myeloma Associated AL Amyloidosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1860-1860
Author(s):  
Paolo Milani ◽  
Francesca Fazio ◽  
Marco Basset ◽  
Tamara Berno ◽  
Alessandra Larocca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Board Of Directors ◽  
Light Chain ◽  
Single Agent ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Travel Grant

INTRODUCTION: Daratumumab has been recently introduced in the treatment of patients with multiple myeloma (MM). Two phase II trials of this drug in relapsed/refractory AL amyloidosis were recently completed, but final reports have not been published so far. One randomized phase III trial in treatment-naïve patients with this diseases has recently completed enrollment and the results are eagerly awaited. However, several retrospective series showed encouraging response rates with daratumumab alone or in combination with bortezomib or immune modulatory drugs in AL amyloidosis. After this drug was marketed for MM in Italy, it became routinely accessible also to patients with myeloma-associated AL amyloidosis (MM-AL). We evaluated the efficacy of daratumumab in a consecutive series of patients with MM-AL in three centers of the Italian Amyloidosis Study Group. METHODS: Consecutive patients with a diagnosis of MM-AL treated with daratumumab were included in the study. Patients received daratumumab 16 mg/Kg body weight e.v. once a week for the first two months and then every other week for the next four months and subsequently every 28 days. The standard DVd (daratumumab, bortezomib and dexamethasone) and DRd (daratumumab, lenalidomide and dexamethasone) regimens were also used in subsets of patients. Hematologic and organ responses were assessed according to the International Society of Amyloidosis (ISA) criteria. RESULTS: Seventy-two patients were included in the study (61 in Pavia, 10 in Padua and 1 in Turin), Table. Median age was 61 years (range: 37-79 years) and 45 (63%) patients were males. The heart and the kidney were involved in 49 patients each (68%). Median bone marrow plasma cell infiltrate was 18% (range: 11-50%). Median time from diagnosis to treatment initiation was 32 months (range: 3-185 months). Fifty (69%) patients were refractory to the line of therapy immediately preceding daratumumab. Median number of prior treatments was 2 (range: 1-9) and daratumumab was used as second line option in 20 (28%) cases. Forty-seven (65%) patients received daratumumab as single agent. The remaining patients received DVd 14 (19%) and DRd in 11 (15%) cases. After 8 infusions 59 (82%) patients achieved a hematologic response (HR): complete response (CR) in 12 (16%), very good partial response (VGPR) in 30 (42%) and partial response (PR) in 17 (24%). Cardiac response was observed in 9 of 37 evaluable patients (24%) and renal response in 21 of 38 patients (55%). Among patients in VGPR, 4 did not qualify for CR due to the persistence of an abnormal free light chain (FLC) ratio (FLCR) despite normalization of involved FLC (iFLC) due to lower than normal levels of uninvolved FLC, while serum and urine immunofixation were negative. After 16 infusions there was only a modest improvement of overall HR rate (60 patients, 83%), but quality of response improved: with CR in 22 patients (30%), VGPR in 21 (29%), and PR in 17 (24%). Of the 4 patients in iFLC-response after 8 infusions, 2 qualified for CR with normalization of FLCR after 16 infusions. In the other 2 patients FLCR did not normalize and we found persistence of the amyloid light chain at high-resolution immunofixation of serum and/or urine. No difference in HR was seen between patients treated with daratumumab single agent and those who received daratumumab combinations (after 16 infusions 81% vs. 88%, P=0.470). After 16 infusions, cardiac response was observed in 11 of 37 evaluable patients (29%) and renal response in 23 of 38 patients (60%). After a median follow-up of living patients after daratumumab initiation of 12 months, 5 subjects died due to disease progression and projected survival at 1 year was 95%. CONCLUSION: Daratumumab is effective in heavily pretreated patients with MM associated AL amyloidosis. Quality of response improved over time with 60% of patients achieving CR or VGPR after 16 infusions. Suppression of uninvolved FLC may result in delayed normalization of FLC ratio in some patients. Disclosures Milani: Pfizef: Honoraria; Janssen: Honoraria. Larocca:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. Oliva:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Petrucci:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Palladini:Celgene: Other: Travel grant; Janssen-Cilag: Honoraria; Sebia: Honoraria; Janssen-Cilag: Other: Travel grant.

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