title: Complete response in a critically ill patient with ALK-negative anaplastic large cell lymphoma treated with single agent brentuximab-vedotin.
abstract: Anaplastic large cell lymphoma (ALCL) is a rare hematological malignancy and a distinct subtype of mature T-cell lymphomas. ALCL is comprised of two clinically distinct but morphologically similar sub-class under 2008 WHO classification: cutaneous and systemic. Primary systemic ALCL is further sub-categorized into tumors that carry the anaplastic lymphoma kinase (ALK) gene rearrangement or not; ALK-positive versus ALK-negative disease respectively. Traditionally, both forms of primary systemic ALCL have been treated upfront with an anthracycline based combination chemotherapy such as CHOP. More recently an antibody drug conjugate, brentuximab-vedotin (BV), directed against CD30 antigen has shown promise in CD30 expressing hematologic malignancies such as Hodgkin's lymphoma and ALCL. At the present time, this novel antibody-drug conjugate has been approved in the treatment of patients with ALCL after failure of at least one prior multi-agent chemotherapy regimen in the United States. We present a case describing a previously healthy 48 year-old female diagnosed with ALK-negative ALCL who achieved complete response with upfront single agent brentuximab-vedotin. It is the first case described in the literature utilizing BV in the first line setting particularly in a patient with multi-organ failure and critically ill at time of diagnosis. This case highlights the full potential that targeted therapies can exert over hematological malignancies while also minimizing treatment related toxicities.
  
  
  BACKGROUND
  AE: adverse event; ALCL: anaplastic large cell lymphoma; ALK: anaplastic lymphoma kinase; ASCT: autologous stem cell transplant; BEAM: BCNU/carmustine, etoposide, ara-C, and melphalan; BV: brentuximab vedotin; CHEOP: cyclophosphamide, daunorubicin, vincristine, prednisone, etoposide; CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone; CR:complete response; G3+: grade 3 or higher; MTD: maximum tolerated dose; ORR: overall response rate; OS: overall survival; PFS: progression-free survival.
authors.affiliation: a Hematology and Medical Oncology , Loma Linda University , Loma Linda , CA , United States.
authors.forename: Karlos Z
authors.initials: KZ
authors.lastname: Oregel
authors.affiliation: b Hematology and Medical Oncology Clinical Pharmacy , Loma Linda University , Loma Linda , CA , United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Everett
authors.affiliation: c Department of Pathology and Human Anatomy , Loma Linda University , Loma Linda , CA , United States.
authors.forename: Xinhai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Hematology and Medical Oncology , Loma Linda University , Loma Linda , CA , United States.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Nagaraj
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000079963:Brentuximab Vedotin; D016638:Critical Illness; D018572:Disease-Free Survival; D005260:Female; D023061:Gene Order; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D018796:Immunoconjugates; D000079963:Brentuximab Vedotin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALCL; Brentuximab-vedotin; CD-30 positive NHL; anaplastic large cell lymphoma; antibody drug conjugate