Brentuximab-vedotin in combination with cyclophosphamide, doxorubicin, prednisolone for the treatment of aggressive CD30-positive cutaneous T-cell lymphomas

Aggressive CD30-positive cutaneous T-cell lymphomas (CD30+CTCL) are associated with unfavorable prognosis. Anthracycline-based polychemotherapy (CHOP) and brentuximab-vedotin (BV) monotherapy are related to poor outcomes in case of extracutaneous involvement or rapidly-progressing disease. Our objective was to assess the effectiveness of BV + CHP in aggressive CD30+CTCL. We included 7 patients treated with BV + CHP from April 2015 to January 2022: 4 had mycosis fungoides with large-cell transformation, 2 had primary cutaneous anaplastic large-cell lymphoma, and 1 harbored a primary cutaneous aggressive epidermotropic CD8-positive T-cell lymphoma. After a median [IQR] follow-up of 17.2 [13.2-21.0] months, 6/7 patients achieved an ORR lasting ≥4 months. The median [IQR] duration of response was 9.5 [5.9-11.1] months and the median [IQR] progression free survival was 14.9 [11.6-16.4] months. Four patients displayed progression with a median (range) time to next treatment of 15.8 (6.5-16.3) months. Two grade-3 adverse events were reported: febrile neutropenia and thromboembolic event. BV + CHP displayed substantial antitumor activity and favorable safety profile in 7 patients with aggressive CD30+CTCL.

[1]  L. Staudt,et al.  The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee. , 2022, Blood.

[2]  E. Durot,et al.  Survival and Prognostic Factors in Patients with Aggressive Cutaneous T-cell Lymphomas , 2022, Acta dermato-venereologica.

[3]  K. Savage,et al.  The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma , 2021, Annals of oncology : official journal of the European Society for Medical Oncology.

[4]  Limei Qu,et al.  The Short-Term Efficacy and Safety of Brentuximab Vedotin Plus Cyclophosphamide, Epirubicin and Prednisone in Untreated PTCL: A Real-World, Retrospective Study , 2021, Advances in Therapy.

[5]  M. Weichenthal,et al.  Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician’s choice in cutaneous T-cell lymphoma: final data , 2021, Blood advances.

[6]  M. Weichenthal,et al.  Response to brentuximab vedotin versus physician’s choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: An ALCANZA sub-analysis , 2021, European journal of cancer.

[7]  J. Vose,et al.  ALK-negative anaplastic large cell lymphoma: features and outcomes of 235 patients from the International T-Cell Project. , 2021, Blood advances.

[8]  R. Schneiderbauer,et al.  Most rare subtypes of cutaneous lymphoma display variable CD30 expression: analysis of the German Cutaneous Lymphoma Network , 2021, The British journal of dermatology.

[9]  C. Mitteldorf,et al.  A review of CD30 expression in cutaneous neoplasms , 2020, Journal of cutaneous pathology.

[10]  M. Bagot,et al.  Allogeneic Hematopoietic Stem Cell Transplantation in Cutaneous T-Cell Lymphomas , 2020, Cancers.

[11]  H. Putter,et al.  Outcomes of rare patients with a primary cutaneous CD30+ lymphoproliferative disorder developing extracutaneous disease. , 2020, Blood.

[12]  L. Specht,et al.  Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[13]  R. Novoa,et al.  Variability in the Expression of Immunohistochemical Markers: Implications for Biomarker Interpretation in Cutaneous T-Cell Lymphoma. , 2017, The Journal of investigative dermatology.

[14]  M. Girardi,et al.  Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T‐cell lymphoma: long‐term remission after brentuximab vedotin , 2017, International journal of dermatology.

[15]  J. Scarisbrick,et al.  Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  M. Kaminski,et al.  A retrospective comparative outcome analysis following systemic therapy in Mycosis fungoides and Sezary syndrome , 2016, American journal of hematology.

[17]  R. Advani,et al.  The World Health Organization Classification of Lymphoid Neoplasms , 2013 .

[18]  P. Gaulard,et al.  Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[19]  J. Scarisbrick,et al.  A cutaneous lymphoma international prognostic index (CLIPi) for mycosis fungoides and Sezary syndrome. , 2013, European journal of cancer.

[20]  R. Dummer,et al.  EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. , 2011, Blood.

[21]  David I. Smith,et al.  Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. , 2011, Blood.

[22]  R. Advani,et al.  Prognostic factors in primary cutaneous anaplastic large cell lymphoma: characterization of clinical subset with worse outcome. , 2009, Archives of dermatology.

[23]  Angelica Selim,et al.  TNM Classification System for Primary Cutaneous Lymphomas , 2008 .

[24]  Nicola Pimpinelli,et al.  Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). , 2007, Blood.

[25]  Nicola Pimpinelli,et al.  WHO-EORTC classification for cutaneous lymphomas. , 2005, Blood.

[26]  P. Quaglino,et al.  Systemic polychemotherapy in the treatment of primary cutaneous lymphomas: a clinical follow-up study of 81 patients treated with COP or CHOP. , 1998, Leukemia & lymphoma.

[27]  S. Lade,et al.  Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy. , 2015, Blood.