key: cord-0980062-h3hva80r
authors: Lee, Holly; Tay, Jason; Duggan, Peter; McCulloch, Sylvia; Neri, Paola; Bahlis, Nizar J.; Jimenez‐Zepeda, Victor H.
title: The impact of COVID‐19 in the management of AL amyloidosis and Immunoglobulin Deposition Disease: A single‐center experience
date: 2020-11-29
journal: Eur J Haematol
DOI: 10.1111/ejh.13552
sha: f2e1b488b8c7de4867328ebd9be4fe4f1b50c05c
doc_id: 980062
cord_uid: h3hva80r

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.

The COVID-19 pandemic poses unprecedented challenges for patients, clinicians, and healthcare systems. 5 Patients with AL amyloidosis and related disorders such as light chain deposition disease and heavy chain deposition disease (LCDD and HCDD), also known and immunoglobulin deposition disease (IDD), are at a high risk of complications associated with COVID-19, in part due to an increased risk for infections, frailty status, advanced age, comorbidities, and immunosuppression. In addition, the therapies used for the management of COVID-19 can be associated with cardiovascular adverse events which are of particular importance for those patients with AL amyloidosis and IDD who have cardiac involvement. 6, 7 Furthermore, immunotherapies and immunoparesis associated with AL amyloidosis could potentially increase the risk of more severe forms of COVID-19. 8, 9 Currently, most of the recommendations for the management of plasma cell disorders in the era of COVID-19 are not evidence based, 10, 11 and thus, it is important to report the experiences of centers to raise awareness of the possible complications and for better understanding of the implications of the pandemic on the treatment of patients with AL amyloidosis and IDD. In the present study, we aimed to assess the impact of the COVID-19 pandemic on the management of patients with AL amyloidosis and IDD at a plasma cell disorders referral center.

All consecutive patients with AL amyloidosis and IDD seen at our institution from 2013 to 2020 and registered in the local Plasma Cell Disorders Database were evaluated. Patient treatment and disease status since the beginning of the pandemic on March 11, 2020 , as declared by WHO, were collected and analyzed. Patients were treated and followed according to our institutional guidelines. This project has been approved by the Health Research Ethics Board.

Two-sided Fisher exact test was used to test for differences between categorical variables. Two-sided Fisher exact test was used to test for differences between categorical variables. A P value of <.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the logrank test. All statistical analyses were performed by using the SPSS 24.0 software.

Ninety-six patients were registered in the local Amyloid and IDD database. Clinical characteristics are shown in Table 1 . Patients with systemic AL amyloidosis were more likely to have lambda restriction as compared to patients with IDD (73% vs 15%, P = .01). Serum creatinine level and the percentage of bone marrow plasma cells trended higher in the IDD group compared to systemic AL amyloidosis group, as 50% of cases with LCDD were associated with symptomatic multiple myeloma (MM), but the differences were not significant (P = .42 and P = .39, respectively).

Among the 15 patient cases with localized amyloidosis, 5 of them had amyloid localized to the lungs, 2 affecting the breast, 2 with eyelid involvement, 1 with vocal cord, 1 with orbital disease, 1 with nodal, 1 with skin, 1 with gastrointestinal, and 1 with genitourinary involvement. None of these patients have progressed or required systemic therapy at the time of analysis.

All patients with IDD presented with renal involvement, and two of the five LCDD patients also developed heart involvement. Finally, one patient with LCDD had gastrointestinal involvement at the time of diagnosis. Table 2 ). The remaining two of the 45 patients have moved to different cities. One patient with HCDD and three patients with LCDD are receiving active therapy.

We describe our local experience of managing AL amyloidosis and immunoglobulin deposition disease (IDD) during the COVID-19 pandemic.

We emphasize that the management of AL amyloidosis and IDD must be individualized based on the biological aspects of the disease, clinical characteristics, centers' access to care under the current pandemic restrictions, as well as the epidemiological aspects of the outbreak in a particular region. 

Prior to the pandemic, the local standard care for patients with AL amyloidosis involved four to six cycles of induction therapy with cyclophosphamide, bortezomib, and dexamethasone (CyBord) to achieve very good partial response (VGPR) or greater. A proportion of patients received an alternative regimen including cyclophosphamide, bortezomib, and methylprednisolone (CyBorMe). For patients in VGPR after induction therapy, continuous therapy with bortezomib administered every 2 weeks was decided based on individual features associated with the disease (ie, AL amyloidosis with >10% bone marrow plasma cells and lack of organ response). If complete response (CR) was achieved, patients underwent minimal residual disease (MRD) testing by multiparameter flow cytometry as previously described. 12 MRD was not used to modify therapy but rather to characterize depth of response. Once CR was achieved postinduction, the decision to continue treatment versus discontinuing therapy was made on a case by case basis. In patients on second line or beyond who received lenalidomide, the need for continuous therapy after six cycles was individualized based on hematological response, organ response, and tolerability. Similarly, for patients receiving daratumumab-based regimens, the minimum duration of therapy was 2 years, with a goal of therapy of sustaining CR.

Since the pandemic, patients' treatments were discontinued if they achieved VGPR or better. Seven patients were receiving daratumumab-based treatment regimens at the time of the pandemic (Table 2 ). One patient achieved VGPR after seven cycles of daratumumab, lenalidomide, and dexamethasone (DRd) and discontinued 

As of March 11, 2020, when WHO declared the pandemic, the cancer center initiated a telemedicine program. All patients were contacted by phone and laboratory testing was restricted to local laboratory facilities where the immunocompromised patients were offered reserved spots by the Alberta Health Services. The amyloidosis clinic is run weekly at our institution, and ~90% of the patients were assessed through telemedicine. New cases were seen in the clinic for initial assessments, and investigations and diagnostic imaging studies were done according to prioritization. All patients not on active treatment were assessed via phone follow-ups, and laboratory testing was delayed at the peak of the outbreak.

Patients with AL amyloidosis with heart involvement are assessed monthly at our clinics with a 6-minute walk test (6MWT). At the time of the pandemic declaration, all 6MWT were canceled in the clinics, and instead, patients were instructed to self-monitor their ability to walk and perform activities of daily living.

The province of Alberta has one of the highest testing rates in the world (as of November 3, 2020, there were 1 789 173 tests completed for a total population of approximately 4.37 million). 4 

Since the onset of the pandemic, there has been a rapid emergence of studies to identify the vulnerable patient population who are at high risk of severe COVID-19. Several reports suggest that cancer patients, particularly those with hematological malignancies, may have more severe forms of COVID-19 with higher case fatality rates. [14] [15] [16] [17] [18] [19] Unlike symptomatic multiple myeloma which is a hema- The incidence of AL amyloidosis is rare (around 1/5th as common as symptomatic myeloma), 22 and the diagnosis is challenging and often delayed. 23 Furthermore, around 25% of the patients present with advanced organ involvement at diagnosis, and systemic AL amyloidosis is progressive with high morbidity and mortality without treatment. 22 The management of patients with AL amyloidosis and IDD is uniquely challenging, ever more so during the COVID-19 pandemic, as dedicated large studies to understand the optimal management of this small yet susceptible patient population during the outbreak are unlikely to take place in a timely manner.

The Equally important in the care of AL amyloidosis and IDD patients is to address patients' emotional burdens that can be associated with feelings of vulnerability to illness and isolation that accompanies social distancing measures. All patients should be informed and engaged in the discussion of their individual infection risks 26 and referred for allied health and community supports when possible.

HL and VZ performed data collection and analysis. All authors contributed to writing and reviewing of the manuscript. There are no financial or material support to be acknowledged.

None to declare.

The data are not available due to privacy and ethical restrictions.

Holly Lee https://orcid.org/0000-0001-8353-0848

Victor H. Jimenez-Zepeda https://orcid. org/0000-0002-6220-5955

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