Tuberculosis during lenalidomide maintenance in a patient with multiple myeloma

Fernández, Gladys Ibarra; Ribera, Josep Maria; Sabater, Laura Abril

doi:10.1016/j.medcli.2019.12.010

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Universitat Autònoma de Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tuberculosis durante el mantenimiento con lenalidomida en un paciente con mieloma múltiple" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 776 "Ancho" => 2167 "Tamanyo" => 163550 ] ] "descripcion" => array:1 [ "en" => "(A and B) PET-CT with pulmonary nodule in the left lower lobe." ] ] ] "textoCompleto" => "The development of the granuloma and its subsequent degeneration and necrosis, is the hallmark of infection caused by Mycobacteriumtuberculosis.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> Immunosuppressed individuals are at high risk of developing active tuberculosis once infected.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> In patients with multiple myeloma, cell-mediated immunity is suppressed by both the primary disease and the treatments, such as steroids, proteasome inhibitors, and immunomodulatory drugs.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Lenalidomide and pomalidomide, structural analogs of thalidomide, have been approved to treat multiple myeloma by FDA in 2006 and 2013, and significant toxicities such as neutropenia, myelosuppression, thrombocytopenia, and serious infections are commonly associated with their use. The mechanisms by which lenalidomide increases the risk of infections remain unclear.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> Maintenance with lenalidomide after autologous hematopoietic stem cell transplantation (HSCT) is currently used and although it improves progression-free survival, long-term adverse effects are still unknown. We report the case of a patient with a diagnosis of multiple myeloma receiving lenalidomide, who developed cough and a pulmonary nodule of tuberculous origin.A 49-year-old Chinese man, former smoker, was diagnosed with IgD lambda multiple myeloma, International Score System III, in November 2017. He initially received 5 cycles of bortezomib, thalidomide and dexamethasone, as well as radiotherapy (30Gy) on a pelvic plasmocytoma. Autologous HSCT was subsequently performed, after which the patient showed partial response. In October 2018 the patient started maintenance treatment with lenalidomide 10mg/day, p.o. In April 2019, being in complete remission of the myeloma, the patient presented cough and chest pain without fever. A PET/CT scan showed a pulmonary nodule in the left lower lobe, 4cm in diameter with signs of necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Fiberoptic bronchoscopy with bronchoalveolar lavage showed tracheal distorsion, extrinsic compression and thickening of the bronchial mucosa. Microbiological culture was positive for Mycobacterium tuberculosis complex. Transbronchial biopsy demonstrated granulomatous inflammation with caseous necrosis and positive Ziehl-Neelsen stain. The patient was started antituberculous therapy with rifampicine, isoniazid, pyrazinamide and ethambutol hydrochloride, which led to rapid improvement of symptoms. Maintenance treatment with lenalidomide was discontinued and close monitoring of the monoclonal component was performed. Currently, 7 months after having discontinued maintenance the patient remains in complete response of myeloma with disappearance of the chest lesion.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Lenalidomide is an immunomodulatory drug widely used in myeloma treatment, either as front line or at relapse as well as in maintenance after autologous HSCT. Lenalidomide has impact on the immune system predisposing patients to opportunistic infections. Lenalidomide maintenance therapy has been associated with twice the risk of severe infection compared to thalidomide therapy.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>Mycobacterium tuberculosis has not commonly reported in myeloma patients. Most cases reported involve newly diagnosed patients or patients in relapse under treatment for disease in activity. This was not the case of the patient herein reported, who was in complete response and only received maintenance therapy. In our patient, the appearance of the pulmonary nodule could have suggested relapse of the disease as a plasmocytoma, with erroneous indication of other line of antimyeloma therapy. Given the risks of misdiagnosis or delayed diagnosis, we highlight the importance of performing invasive diagnostic procedures, such as biopsy, to obtain samples for microbiological analysis in all cases of nodule pulmonary lesions, especially in the immunocompromised host even if the patients do not have clear signs of infection.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. In fact, at present there are no consensus regarding the management of this type of infections in myeloma patients who do not have active disease. We suggest routine screening for latent TB infection before starting lenalidomide maintenance." 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Mao" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Hematol" "fecha" => "2018" "volumen" => "97" "paginaInicial" => "925" "paginaFinal" => "944" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infection risk with inmunomodulatory and proteasome inhibitor-base therapies across treatment phases for multiple myeloma: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B.W. Ted" 1 => "S.J. Harrison" 2 => "L.J. Worth" 3 => "K.A. 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