Plasma cell myeloma initially diagnosed as light-chain deposition disease on liver biopsy: A case report and literature review.

RATIONALE: Light-chain deposition disease (LCDD) is a rare condition characterized by the abnormal deposition of monoclonal light chains (LCs) in multiple organs, leading to progressive organ dysfunction. Herein, we report a case of plasma cell myeloma initially diagnosed as LCDD on liver biopsy performed for prominent cholestatic hepatitis. PATIENT CONCERNS: A 55-year-old Korean man complained of dyspepsia as the main symptom. On abdominal computed tomography performed at another hospital, the liver showed mildly decreased and heterogeneous attenuation with mild periportal edema. Preliminary liver function tests revealed abnormal results. The patient was treated for an unspecified liver disease; however, his jaundice gradually worsened, prompting him to visit our outpatient hepatology clinic for further evaluation. Magnetic resonance cholangiography revealed liver cirrhosis with severe hepatomegaly of unknown cause. A liver biopsy was performed for the diagnosis. Hematoxylin and eosin staining revealed diffuse extracellular amorphous deposits in perisinusoidal spaces with compressed hepatocytes. The deposits, which morphologically resembled amyloids, were not stained by Congo red but stained strongly positive for kappa LCs and weakly positive for lambda LCs. DIAGNOSES: Therefore, the patient was diagnosed with LCDD. Further systemic examination revealed a plasma cell myeloma. INTERVENTIONS: Fluorescence in situ hybridization, cytogenetics, and next-generation sequencing tested in bone marrow showed no abnormalities. The patient initially received bortezomib/lenalidomide/dexamethasone as the treatment regimen for plasma cell myeloma. OUTCOMES: However, he died shortly thereafter because of coronavirus disease 2019 complications. LESSONS: This case demonstrates that LCDD may present with sudden cholestatic hepatitis and hepatomegaly, and may be fatal if patients do not receive appropriate and timely treatment because of delayed diagnosis. Liver biopsy is useful for the diagnosis of patients with liver disease of unknown etiology.

[Multiple myeloma: response to treatment and survival of patients according to the interim analysis of the Russian observational, retrospective-prospective, multicenter cohort study (MULTISPECT)].

AIM: The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. MATERIALS AND METHODS: The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. RESULTS: The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. CONCLUSION: The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.

Diagnosis and management of Waldenström macroglobulinaemia-A British Society for Haematology guideline.

SCOPE: The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Waldenström macroglobulinaemia. In individual patients, circumstances may dictate an alternative approach. METHODOLOGY: This guideline was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. Recommendations are based on a review of the literature using Medline, Pubmed, Embase, Central, Web of Science searches from beginning of 2013 (since the publication of the previous guidelines) up to November 2021. The following search terms were used: Waldenström('s) macroglobulin(a)emia OR lymphoplasmacytic lymphoma, IgM(-related) neuropathy OR cold h(a)emagglutinin disease OR cold agglutinin disease OR cryoglobulin(a)emia AND (for group a only) cytogenetic OR molecular OR mutation OR MYD88 OR CXCR4, management OR treatment OR transfusion OR supportive care OR plasma exchange OR plasmapheresis OR chemotherapy OR bendamustine OR bortezomib OR ibrutinib OR fludarabine OR dexamethasone OR cyclophosphamide OR rituximab OR everolimus, bone marrow transplantation OR stem cell transplantation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by UK Charity WMUK; these organisations do not necessarily approve or endorse the contents.

The development of a home-based therapeutic platform for multiple myeloma.

BACKGROUND: Multiple Myeloma (MM) accounts for 1-2% of all malignancies but is the second most common hematological malignancy. It is characterized by a proliferation of malignant plasma cells. The treatment paradigm of MM in Australia is traditionally hospital-based, complex, and costly. While MM comprises 1-2% of cancer diagnoses, it appears in the top 10 cancer diagnoses requiring hospital admission. The cumulative time spent receiving treatment is a significant burden for patients. The ability to receive treatment at home and maximize time away from hospital-based settings is a key preference for patients receiving anticancer therapies over a prolonged period of time. METHODS: The Peter MacCallum Cancer Centre and Royal Melbourne Hospital's combined Clinical Hematology Unit has collaborated with their Hospital in the Home departments to develop several innovative programs to address this. RESULTS: We describe our current active programs and potential developments in home-based MM therapy. CONCLUSION: We have enabled large numbers of patients to receive complex therapies in their own home and the COVID-19 pandemic has increased the pace of the roll out without any compromise in safety. We anticipate that the next raft of immunotherapies will be able to transition into the @Home treatment setting in the coming years.

Outcome of COVID-19 infection in 50 multiple myeloma patients treated with novel drugs: single-center experience.

Infections are the primary cause of morbidity and mortality in multiple myeloma (MM) patients (pts). The aim of our retrospective analysis was to evaluate incidence and course of COVID-19 infection in a cohort of 351 MM outpatients treated with novel drugs. COVID-19 disease was detected in 50/351 pts (14%); median age was 68 years. Gender, ISS stage, and last treatment lines were as follows: male 32, female 18; ISS-I 19, ISS-II 20, ISS-III 11; daratumumab-based 15, lenalidomide-based 12, bortezomib-based 17, other 6. Positive PCR test at COVID-19 diagnosis was present in all pts; anti-myeloma treatment was interrupted. Hospitalizations for COVID-19 pneumonia were necessary for 28/50 pts (56%), 18/50 pts (36%) in standard unit (SU) 10/50 pts (20%) in intensive care unit (ICU), and 9/50 pts (18%) died. The statistically significant parameters for COVID-19 hospitalization were as follows: responsive versus non-responsive disease (p = 0.027), ECOG performance status 0-2 versus ≥ 3 (p = 0.014), presence of comorbidities (0-1 versus ≥ 2, p = 0.043). The statistically significant factors for COVID-19 death were as follows: ECOG 0-2 versus ≥ 3 (p = 0.001), presence of comorbidities (0-1 versus ≥ 2, p = 0.007), serious course of COVID-19 disease with ICU hospitalization (SU versus ICU, p = 0.001). None of the other studied risk factors was associated with poor outcome (age, gender, ISS stage, immunoparesis, type of anti-myeloma treatment). Full recovery from COVID-19 infection was observed in 41/50 pts (82%) in median of 32 days. The course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths.

Successful second outpatient autologous hematopoietic cell transplant for relapsed POEMS syndrome in a patient with coexisting HIV, HBV and syphilis infections during the COVID-19 pandemic.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a multisystem autoinflammatory disease due to an underlying plasma cell disorder that lacks a standard treatment strategy because of its rarity. We report a case of relapsed POEMS syndrome successfully treated with a second ambulatory autologous hematopoietic-cell transplantation (AHCT) after a daratumumab desensitization protocol performed during the coronavirus disease (COVID-19) pandemic in a patient with coexisting human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis infections. He is a 37-year old Latin-American male who had been treated with radiation, CyBorD regimen, AHCT and bortezomib therapy before being referred to our service. It was decided to administer daratumumab therapy and subsequently perform the transplant. Placement of central venous access, fluid infusion, conditioning regimen with melphalan and previously cryopreserved autograft infusion were carried out in an outpatient basis. Following second AHCT, the patient demonstrated clinical, VEGF, hematological response and remains SARS-CoV-2 infection-free and in POEMS remission with excellent quality-of-life at last follow up (6 months). We evidenced that thanks to an outpatient transplant program, the best therapeutic modalities can be offered to patients with hematologic malignancies in the context of present or future pandemics. Finally, high-complexity patients with HIV infection should have access to the same treatment strategies as non-infected patients. A second AHCT in the outpatient setting is feasible, safe and highly effective to treat patients with relapsed POEMS syndrome.

The impact of COVID-19 in the management of AL amyloidosis and Immunoglobulin Deposition Disease: A single-center experience.

INTRODUCTION: Patients with AL amyloidosis and immunoglobulin deposition diseases (IDD) are vulnerable during the COVID-19 pandemic due to the immune compromise from the plasma cell disorder and therapy-related immune defects. We describe a local experience in providing care for patients with AL amyloidosis and IDD. METHOD: Patient treatment and disease status since the beginning of the pandemic on March 11, 2020, as declared by WHO, were collected and analyzed. RESULTS: Ninety-six patients with AL amyloidosis and IDD were included. Four patients with IDD and 22 patients with systemic AL amyloidosis were receiving treatment during the pandemic. Since the pandemic, patients' treatments were discontinued if they achieved VGPR or better postinduction. Seven patients discontinued all treatment after achieving VGPR, and others required treatment modifications. 28 patients have been tested for COVID-19, and all tests have been negative. Three patients died since the pandemic, two from organ complications of systemic AL amyloidosis and one from an unrelated cause. CONCLUSION: The management of AL amyloidosis and IDD must be individualized on the clinical characteristics, centers' access to care under the pandemic restrictions, and the epidemiological aspects of the outbreak.