Interim report of a phase 2 clinical trial of lenalidomide for T‐cell non‐Hodgkin lymphoma

Dueck, Greg; Chua, Neil; Prasad, Angeli; Finch, Daygen L.; Stewart, D. A.; White, Darrell; Jagt, Richard van der; Johnston, James B.; Belch, Andrew R.; Reiman, Tony

doi:10.1002/cncr.25377

Cited by 91 publications

(65 citation statements)

References 41 publications

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“…These data suggest, as previously shown in acute myelog- Therapeutic effect of lenalidomide in the human BNKL mouse model So far, lenalidomide has been used to treat hematologic neoplastic diseases such as multiple myeloma, myelodysplastic syndromes (MDS), and lymphoma (15,16,28,29), with some encouraging evidence of possible clinical activity in colorectal carcinoma (30). We therefore decided to test this drug in our model of human BNKL.…”

Section: Development Of a Xenograft Mouse Model Of Human Bnklsupporting

confidence: 59%

Therapeutic Effect of Lenalidomide in a Novel Xenograft Mouse Model of Human Blastic NK Cell Lymphoma/Blastic Plasmacytoid Dendritic Cell Neoplasm

Agliano

Martín‐Padura

Marighetti

et al. 2011

Clinical Cancer Research

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Purpose: Blastic natural killer (NK) cell lymphoma/blastic plasmacytoid dendritic cell neoplasm (BNKL) is a rare and aggressive neoplasia characterized by infiltration of blast CD4 þ /CD56 þ cells in the skin, the bone marrow, and peripheral blood. Currently, more efforts are required to better define molecular and biological mechanisms associated with this pathology. To the best of our knowledge, no mouse model recapitulated human BNKL so far. Experimental Design: Primary bone marrow cells from a BNKL patient were injected in nonobese diabetes/severe combined immunodeficient interleukin (IL) 2rgÀ/À mice with the intent to generate the first BNKL orthotopic mouse model. Moreover, because of the lack of efficient treatments for BNKL, we treated mice with lenalidomide, an immunomodulatory and antiangiogenic drug.Results: We generated in mice a fatal disease resembling human BNKL. After lenalidomide treatment, we observed a significant reduction in the number of peripheral blood, bone marrow, and spleen BNKL cells. Tumor reduction parallels with a significant decrease in the number of circulating endothelial and progenitor cells and CD31 þ murine endothelial cells. In mice treated with lenalidomide, BNKL levels of active caspase-3 were significantly augmented, thus showing proapoptotic and cytotoxic effects of this drug in vivo. An opposite result was found for proliferating cell nuclear antigen, a proliferation marker.Conclusions: Our BNKL model might better define the cellular and molecular mechanisms involved in this disease, and lenalidomide might be considered for the future therapy of BNKL patients.

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Section: Development Of a Xenograft Mouse Model Of Human Bnklsupporting

confidence: 59%

Therapeutic Effect of Lenalidomide in a Novel Xenograft Mouse Model of Human Blastic NK Cell Lymphoma/Blastic Plasmacytoid Dendritic Cell Neoplasm

Agliano

Martín‐Padura

Marighetti

et al. 2011

Clinical Cancer Research

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“…[67][68][69][70] The drug was administered orally starting dose of 25 mg/day for 21 consecutive days on a 28-day cycle. Responses rates varied between 22% and 30%, with CR rates ranging from 8% to 30%; for PTCL-NOS patients specifically, ORR varied from 20% to 43%.…”

Section: Org Frommentioning

confidence: 99%

Peripheral T-cell lymphoma, not otherwise specified

Broccoli

Zinzani

2017

Blood

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Peripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any other of the existing entities defined by the World Health Organization classification. Anthracycline-containing regimens, namely cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), nowadays represent the standard first-line treatment; for patients who achieve a satisfactory response, a consolidation by means of autologous stem cell transplantation may offer a greater chance of long-term survival. Several patients, however, display treatment refractoriness or relapse soon after obtaining a response, and just a few of them are suitable transplant candidates. This is why several new agents, with innovative mechanisms of action, have been investigated in this context: pralatrexate, romidepsin, belinostat, and brentuximab vedotin have been approved for relapsed and refractory peripheral T-cell lymphomas based on their activity, although they do not significantly affect survival rates. The incorporation of such new drugs within a CHOP backbone is under investigation to enhance response rates, allow a higher proportion of patients to be transplanted in remission, and prolong survival.

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“…Pralatrexate [79] and romidepsin [80] have now been approved for use in the United States for relapsed/refractory PTCL. Other new agents, including lenalidomide [81], desatinib [82], and the aurora kinase inhibitor alisertib [83] all show some promise. Autologous transplantation at the time of treatment failure can cure some patients with chemotherapy-sensitive disease [54].…”

Section: Peripheral T-cell Lymphoma Not Otherwise Specifiedmentioning

confidence: 99%

The aggressive peripheral T‐cell lymphomas: 2015

Armitage

2015

American J Hematol

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Background: T‐cell lymphomas make up approximately 10%–15% of lymphoid malignancies. The frequency of these lymphomas varies geographically, with the highest incidence in parts of Asia.Diagnosis: The diagnosis of aggressive peripheral T‐cell lymphoma (PTCL) is usually made using the World Health Organization classification. The ability of hematopathologists to reproducibly diagnosis aggressive PTCL is lower than that for aggressive B‐cell lymphomas, with a range of 72%–97% for the aggressive PTCLs.Risk Stratification: Patients with aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat controversial, positron emission tomography scans seem to be useful as they are in aggressive B‐cell lymphomas. The most commonly used prognostic index is the International Prognostic Index. The specific subtype of aggressive PTCL is an important risk factor, with the best survival seen in anaplastic large‐cell lymphoma—particularly young patients with the anaplastic lymphoma kinase positive subtype.Risk‐Adapted Therapy: Anaplastic large‐cell lymphoma is the only subgroup to have a good response to a CHOP‐like regimen. Angioimmunoblastic T‐cell lymphoma has a prolonged disease‐free survival in only ∼20% of patients, but younger patients who have an autotransplant in remission seem to do better. PTCL‐not otherwise specified is not one disease. Anthracycline‐containing regimens have disappointing results, and a new approach is needed. Natural killer/T‐cell lymphoma localized to the nose and nasal sinuses seems to be best treated with radiotherapy‐containing regimens. Enteropathy‐associated PTCL and hepatosplenic PTCL are rare disorders with a generally poor response to therapy, although selected patients with enteropathy‐associated PTCL seem to benefit from intensive therapy. Am. J. Hematol. 90:666–673, 2015. © 2015 Wiley Periodicals, Inc.

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Interim report of a phase 2 clinical trial of lenalidomide for T‐cell non‐Hodgkin lymphoma

Cited by 91 publications

References 41 publications

Therapeutic Effect of Lenalidomide in a Novel Xenograft Mouse Model of Human Blastic NK Cell Lymphoma/Blastic Plasmacytoid Dendritic Cell Neoplasm

Therapeutic Effect of Lenalidomide in a Novel Xenograft Mouse Model of Human Blastic NK Cell Lymphoma/Blastic Plasmacytoid Dendritic Cell Neoplasm

Peripheral T-cell lymphoma, not otherwise specified

The aggressive peripheral T‐cell lymphomas: 2015

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