Clinical Activity of Lenalidomide in Visceral Human Immunodeficiency Virus–Related Kaposi Sarcoma

Steff, M.; Joly, Véronique; Lucca, Julie Di; Feldman, Judith F.; Burg, Samuel; Sarda‐Mantel, Laure; Peytavin, Gilles; Marinho, E.; Crickx, B; Raymond, Éric; Lariven, Sylvie; Maubec, Ève

doi:10.1001/jamadermatol.2013.5751

Cited by 14 publications

(8 citation statements)

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“…While investigating possible mechanisms for the activity of Thal, Len, and Pom in patients with KS, [2][3][4]56,57 we found that these drugs increase the surface expression of MHC-I in PEL cell lines latently and lytically infected with KSHV and also restore the NK cell and T-cell co-stimulatory ligands, ICAM-1 and B7-2, in cells latently infected with KSHV. 14 Of the three drugs, Pom was most active.…”

Section: Discussionmentioning

confidence: 91%

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells

et al. 2018

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Most chronic viruses evade T-cell and natural killer (NK) immunity through downregulation of immune surface markers. Previously we showed that Pomalidomide (Pom) increases surface expression of major histocompatibility complex class I (MHC-I) in Kaposi sarcoma-associated herpesvirus-infected latent and lytic cells and restores ICAM-1 and B7-2 in latent cells. We explored the ability of Pom to increase immune surface marker expression in cells infected by other chronic viruses, including human T-cell leukemia virus type-1 (HTLV-1), Epstein-Barr virus (EBV), human papilloma virus (HPV), Merkel cell polyoma virus (MCV), and human immunodeficiency virus type-1 (HIV-1). Pom increased MHC-1, ICAM-1, and B7-2/CD86 in immortalized T-cell lines productively infected with HTLV-1 and also significantly increased their susceptibility to NK cell-mediated cytotoxicity. Pom enhancement of MHC-I and ICAM-1 in primary cells infected with HTLV-1 was abrogated by knockout of HTLV-1 orf-1. Pom increased expression of ICAM-1, B7-2 and MHC class I polypeptide related sequence A (MICA) surface expression in the EBV-infected Daudi cells and increased their T-cell activation and susceptibility to NK cells. Moreover, Pom increased expression of certain of these surface markers on Akata, Raji, and EBV lymphoblastic cell lines. The increased expression of immune surface markers in these virus-infected lines was generally associated with a decrease in IRF4 expression. By contrast, Pom treatment of HPV, MCV and HIV-1 infected cells did not increase these immune surface markers. Pom and related drugs may be clinically beneficial for the treatment of HTLV-1 and EBV-induced tumors by rendering infected cells more susceptible to both innate and adaptive host immune responses.

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Section: Discussionmentioning

confidence: 91%

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells

et al. 2018

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“…One of the easiest potential solutions to this cycle of problems would be to use simpler chemotherapies such as oral etoposide or lenalidomide for early-stage disease, but lenalidomide has been poorly studied in similar contexts [ 31 ], and two recent multicentric trials that included etoposide at African sites have been stopped early because of poor performance of etoposide [ 32 , 33 ]. Another solution would be to increase access to “gold standard” chemotherapies that are available in the global north, such as PLD or taxanes.…”

Section: Discussionmentioning

confidence: 99%

HIV-associated Kaposi’s sarcoma in Maputo, Mozambique: outcomes in a specialized treatment center, 2010–2015

Fardhdiani¹,

Molfino²,

Zamudio³

et al. 2018

Infect Agents Cancer

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BackgroundKaposi’s sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo.MethodsWe performed a retrospective analysis of data collected on patients enrolled at the CRAM between 2010 and 2015, extracting routinely-collected clinical information from patient care databases. KS treatment followed national guidelines, and KS staging followed AIDS Clinical Trials Group and MOH criteria. Baseline description of the cohort and patient outcomes was performed. Risk factors for negative outcomes (death or loss to follow-up) were explored using Cox regression.ResultsBetween 2010 and 2015, 1573 patients were enrolled, and 1210 began chemotherapy. A majority were young adult males. At enrollment, CD4 was < 200 cells/μl in 45% of patients. Among patients receiving chemotherapy, 78% received combination doxorubicin-bleomycin-vincristine. Among patients receiving chemotherapy, 43% were lost to follow-up and 8% were known to have died. In multivariate regression, the only risk factors identified with poor outcomes were CD4 < 100 cells/μl at enrollment (Risk ratio 1.5, 95%CI 1.1–2.1, p = 0.02 and having S1 disease (RR 1.7, 95%CI 1.2–2.3, p = 0.001).DiscussionWe describe a large cohort of patients receiving care for HIV-associated KS in a specialized clinic in an urban setting. Outcomes were nonetheless unsatisfactory. Efforts should be made to decrease late referrals and entry into care and to increase access to more effective and better-tolerated treatments like liposomal doxorubicin.

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“…These latter drugs are still in the phase of clinical trials. [23][24][25] This case emphasizes the need to strongly consider pulmonary KS as a possible cause for respiratory illness in any HIV-positive patient with cutaneous KS. лёгочных узлов после комбинированной антиретровирусной терапии.…”

Section: Discussionmentioning

confidence: 91%

Pulmonary Kaposi's Sarcoma - Initial Presentation of HIV Infection 

Komitova

Chudomirova²,

Abadjieva

2019

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Kaposi's sarcoma is the most common malignancy associated with human immunodeficiency virus. It commonly affects the skin but can present with visceral involvement, including the lungs. A 23-year-old homosexual male presented with fever, intractable cough and dyspnea. On examination, multiple skin lesions were revealed. Chest computed tomography visualized multiple nodules, bronchoscopy showed endobronchial lesions. Histopathological study of the skin lesions showed Kaposi's sarcoma and the endobronchial biopsy -a proliferative inflammatory process. Diagnosis of Kaposi's sarcoma was made based on clinical, laboratory, computed tomography and bronchoscopy data as well as on the regression of pulmonary nodules by the combination antiretroviral therapy. The diagnosis of pulmonary Kaposi's sarcoma is still a challenge due to concomitant occurrence of opportunistic infections. This case emphasizes the need to strongly consider pulmonary KS as a possible cause for respiratory illness in any HIV-positive patient with cutaneous Kaposi's sarcoma.

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Clinical Activity of Lenalidomide in Visceral Human Immunodeficiency Virus–Related Kaposi Sarcoma

Cited by 14 publications

References 14 publications

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells

HIV-associated Kaposi’s sarcoma in Maputo, Mozambique: outcomes in a specialized treatment center, 2010–2015

Pulmonary Kaposi's Sarcoma - Initial Presentation of HIV Infection

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Clinical Activity of Lenalidomide in Visceral Human Immunodeficiency Virus–Related Kaposi Sarcoma

Cited by 14 publications

References 14 publications

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells

Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells

HIV-associated Kaposi’s sarcoma in Maputo, Mozambique: outcomes in a specialized treatment center, 2010–2015

Pulmonary Kaposi&#39;s Sarcoma - Initial Presentation of HIV Infection&nbsp;

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Pulmonary Kaposi's Sarcoma - Initial Presentation of HIV Infection