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Letter to the Editor
Tuberculosis during lenalidomide maintenance in a patient with multiple myeloma
Tuberculosis durante el mantenimiento con lenalidomida en un paciente con mieloma múltiple
Gladys Ibarra Fernándeza,b,
Corresponding author
gibarra2601@hotmail.com

Corresponding author.
, Josep Maria Riberaa,b, Laura Abril Sabatera,b
a Servicio de Hematología, ICO-Badalona, Hospital Germans Trias i Pujol, Badalona, Spain
b Instituto de Investigación contra la Leucemia Josep Carreras. Universitat Autònoma de Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The development of the granuloma and its subsequent degeneration and necrosis&#44; is the hallmark of infection caused by <span class="elsevierStyleItalic">Mycobacterium</span><span class="elsevierStyleItalic">tuberculosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Immunosuppressed individuals are at high risk of developing active tuberculosis once infected&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> In patients with multiple myeloma&#44; cell-mediated immunity is suppressed by both the primary disease and the treatments&#44; such as steroids&#44; proteasome inhibitors&#44; and immunomodulatory drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Lenalidomide and pomalidomide&#44; structural analogs of thalidomide&#44; have been approved to treat multiple myeloma by FDA in 2006 and 2013&#44; and significant toxicities such as neutropenia&#44; myelosuppression&#44; thrombocytopenia&#44; and serious infections are commonly associated with their use&#46; The mechanisms by which lenalidomide increases the risk of infections remain unclear&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> Maintenance with lenalidomide after autologous hematopoietic stem cell transplantation &#40;HSCT&#41; is currently used and although it improves progression-free survival&#44; long-term adverse effects are still unknown&#46; We report the case of a patient with a diagnosis of multiple myeloma receiving lenalidomide&#44; who developed cough and a pulmonary nodule of tuberculous origin&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 49-year-old Chinese man&#44; former smoker&#44; was diagnosed with IgD lambda multiple myeloma&#44; International Score System III&#44; in November 2017&#46; He initially received 5 cycles of bortezomib&#44; thalidomide and dexamethasone&#44; as well as radiotherapy &#40;30<span class="elsevierStyleHsp" style=""></span>Gy&#41; on a pelvic plasmocytoma&#46; Autologous HSCT was subsequently performed&#44; after which the patient showed partial response&#46; In October 2018 the patient started maintenance treatment with lenalidomide 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; p&#46;o&#46; In April 2019&#44; being in complete remission of the myeloma&#44; the patient presented cough and chest pain without fever&#46; A PET&#47;CT scan showed a pulmonary nodule in the left lower lobe&#44; 4<span class="elsevierStyleHsp" style=""></span>cm in diameter with signs of necrosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Fiberoptic bronchoscopy with bronchoalveolar lavage showed tracheal distorsion&#44; extrinsic compression and thickening of the bronchial mucosa&#46; Microbiological culture was positive for <span class="elsevierStyleItalic">Mycobacterium tuberculosis complex</span>&#46; Transbronchial biopsy demonstrated granulomatous inflammation with caseous necrosis and positive Ziehl-Neelsen stain&#46; The patient was started antituberculous therapy with rifampicine&#44; isoniazid&#44; pyrazinamide and ethambutol hydrochloride&#44; which led to rapid improvement of symptoms&#46; Maintenance treatment with lenalidomide was discontinued and close monitoring of the monoclonal component was performed&#46; Currently&#44; 7 months after having discontinued maintenance the patient remains in complete response of myeloma with disappearance of the chest lesion&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Lenalidomide is an immunomodulatory drug widely used in myeloma treatment&#44; either as front line or at relapse as well as in maintenance after autologous HSCT&#46; Lenalidomide has impact on the immune system predisposing patients to opportunistic infections&#46; Lenalidomide maintenance therapy has been associated with twice the risk of severe infection compared to thalidomide therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Mycobacterium tuberculosis has not commonly reported in myeloma patients&#46; Most cases reported involve newly diagnosed patients or patients in relapse under treatment for disease in activity&#46; This was not the case of the patient herein reported&#44; who was in complete response and only received maintenance therapy&#46; In our patient&#44; the appearance of the pulmonary nodule could have suggested relapse of the disease as a plasmocytoma&#44; with erroneous indication of other line of antimyeloma therapy&#46; Given the risks of misdiagnosis or delayed diagnosis&#44; we highlight the importance of performing invasive diagnostic procedures&#44; such as biopsy&#44; to obtain samples for microbiological analysis in all cases of nodule pulmonary lesions&#44; especially in the immunocompromised host even if the patients do not have clear signs of infection&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We decided to interrupt the treatment because the patient was in remission and the interaction or toxicity of the concurrent use of lenalidomide and a cocktail of antituberculous drugs is unknown&#46; In fact&#44; at present there are no consensus regarding the management of this type of infections in myeloma patients who do not have active disease&#46; We suggest routine screening for latent TB infection before starting lenalidomide maintenance&#46;</p></span>"
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ISSN: 00257753
Original language: English
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