Efficacy of Brentuximab-Vedotin (BV) in Peripheral T-Cell Lymphomas (PTCLs) Other Than Anaplastic Large Cell Lymphoma (ALCL)
Authors: Zannori Cristina , Martiniani Roberta , Ascani Stefano , Liberati Fabrizio , Rauco Annamaria , Genua Angelo , Liberati Anna Marina 
Published: October 2019

Abstract
Background. BV, an anti-CD30 antibody-drug conjugate, has been approved for the treatment of Hodgkin lymphoma (HL) and ALCL. Of interest, BV has shown activity in PTCLs other than ALCL that express low or even undetectable levels of CD30. In particular BV has been reported effective in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma not otherwise specified (PTCL-nos). Here, we report 4 cases with relapsed/resistant PTCLs (1 AITL, 1 NK-T nasal type, 1 PTCL with T-helper follicular phenotype-PTCL-TFH and 1 PTCL-nos) who responded to BV therapy.
Results. On August 2014, a 53-y-old caucasian male was diagnosed with 5% CD30-positive AITL. The final stage was IIIA, because of a single left axillar node was documented at the PET-TC scan in addition to the excised inguinal lymphadenopathy. A complete metabolic PET remission (PET-CR) was documented after the 3th and confirmed after the 6th cycle of cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone (CHOEP). However, relapsing disease was documented 6 mths later. At that time, diffuse over and under-diaphragm nodal involvement was observed. A PET-CR was achieved after 2 cycles of dexamethasone, cytarabine, and cisplatin (DHAP), but disease progressed shortly after the 4th cycle before the planned autotransplantation (ASCT). A 3th line chemotherapy, consisting of mitoxantrone and high dose ARA-C (modified HAM), was performed and failed to control the disease. Furthermore HAM chemotherapy was associated with severe infectious complications (sepsis from MDR S. Epidermidis and pulmonary aspergillosis). On December 2015, BV was begun. A PET-CR was documented after the 4th and confirmed after the 8th cycle of therapy. The patients is still in CR, in continuous therapy (12th cycle), waiting for HLA matched unrelated donor.
On July 2012 a 62-y-old caucasian man was diagnosed with extranodal NK/T-cell nasal type lymphoma. Both Epstein Barr virus (EBV) and CD30 molecule were not expressed by neoplastic cells. Weekly cisplatin and radiotherapy were concomitantly given followed by 3 cycles of etoposide, ifosfamide, cisplatin and dexamethasone. This treatment resulted in PET-CR. At the time of first relapse (Nov 2013), 3 cycles of methotrexate, L-asparaginase and dexamethasone, followed by ASCT (fotemustine, etoposide, cytarabine, melphalan), induced a 2nd PET-CR. However, two subsequent PET evaluations suggested the presence of active disease shortly after (December 2015) a biopsy proven relapse was documented. A PET-CR was observed after 2 and confirmed after 7 cycles of single agent BV. The patient is still undergoing treatment.
On September 2015, a 49-y-old african man was diagnosed with PTCL-THF, showing AITL signs, with both EBV and CD30 positive (50-75%) Hodgkin/Reed-Sternberg cells. A progressive disease was documented after the 4th cycle of CHOEP. At that time, patient was not candidate to receive further chemotherapy, because of worsening of perfomance status (PS). BV, given as salvage therapy, resulted in a rapid control of all signs and symptoms after the 6th administration. Because of improved PS and a partial metabolic remission, the DHAP combination was begun on June 2016 and ASCT is now planned as consolidation.
On November 2009, a 46-y-old caucasian man was diagnosed with classical HL. The final stage was IEA. The disease was refractory to doxorubicin, bleomycin, vinblastine, dacarbazine and radiotherapy. A PET-CR was achieved in response to ifosfamide, gemcitabine, vinorelbine and prednisone chemotherapy. After 3 yrs, a lymph node biopsy confirmed a relapsed HL. Four cycles of DHAP followed by ASCT resulted in a 2nd PET-CR. After 3 mths, a PTCL-NOS associated with blastic lymphoid B EBV positive cells was diagnosed on an excisional lymph node biopsy. On May 2014 BV as single-agent was started. A PET-CR lasted for 8 mths. Relapsing disease was documented on January 2015. The patient refused further chemotherapy and died because of disease progression on July 2015.
Conclusion. In this experience BV, regardless of CD30 expression, has shown significant clinical activity in recurrent or refractory T-cell lymphomas and no significant toxicity, even in heavily pretreated patients. In consideration of the BV activity in PTCLs, combination studies with other molecules, such as romidepsine, are desirable.

Disclosures
No relevant conflicts of interest to declare.