Sustained, Durable Responses with Alemtuzumab in Refractory Angioimmunoblastic T-Cell Lymphoma.
Authors: Amengual Jennifer E. , Raphael Bruce G. 
Published: October 2019

Abstract 2730
Poster Board II-706
Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype representing 2% of Non-Hodgkin's Lymphoma characterized by lymphadenopathy, hepatosplenomegaly, anemia, hypergammaglobulinemia and immune dysfunction. Prognosis is poor with a median survival of less than 36 months. There is no standard treatment for AITL. Most patients initially respond to treatment, but relapse within short time intervals. Alemtuzumab is a humanized monoclonal antibody that binds to CD52 antigen, a cell surface glycoprotein with high expression on T-cells. We report three patients with refractory AITL, with confirmed T-cell receptor gene rearrangements, who achieved sustained, durable responses with alemtuzumab. The table below lists the treatment regimens, duration of remissions and complications for all 3 cases. Infectious and autoimmune complications were effectively treated in all.PatientPrevious Treatment (Response duration, months)Alemtuzumab (Response duration)InfectionsAutoimmune manifestationsACHOP (10) Cytoxan-P (1) Gemzar-P (1)24 monthsCMVBCHOPE (10) ICE (0) Gemcitabine-P followed by Cyclosporine maintenance (1)>24 monthsAspergillusAgranulocytosis Autoimmune hemolytic anemiaCCHOP (1)>14 monthsCMV Legionella
Patient A was a 73 year-old female who presented with lymphadenopathy and biopsy proven AITL. Her longest remission was 10 months following CHOP. She was started on alemtuzumab 30 mg 3 times per week for 4 weeks in June 2007 after relapsing. Her only complication from treatment was CMV infection. She remained in remission until June 2009 when she relapsed in her liver and colon. She was treated with alemtuzumab and prednisone for 2 weeks, but developed neutropenic fever, CMV and died July 2009. Patient B is a 73 year-old male with a history of ITP who presented in July 2005 with fevers, lymphadenopathy and anemia, and biopsy proven AITL. His longest remission was 10 months with CHOPE. In June 2007, the patient was treated with alemtuzumab for 7 weeks after relapsing. Treatment complications included Aspergillus pneumonia, agranulocytosis and autoimmune hemolytic anemia. He achieved a complete response as evidenced by PET/CT scan. He remains in remission 2 years later. Patient C is a 62 year-old woman with a history of MGUS who presented in 2007 with rapidly growing lymphadenopathy and a biopsy that revealed AITL. She never achieved a sustained remission with chemotherapy. June 2008, the patient was treated with alemtuzumab for 6 weeks, complicated by CMV and Legionella pneumonia. She remains in remission now over 14 months.
Here we have shown remarkable success with short courses of alemtuzumab. Three patients remained disease free for an average of 21 months; two remissions are on-going. This report demonstrates sustained responses for patients with AITL, suggesting that alemtuzumab is a valid and rational treatment choice in heavily pretreated patients. We propose using anti-CD52 therapy as consolidation after primary response to conventional chemotherapy in patients with AITL.

Disclosures:
Off Label Use: Alemtuzumab is not licensed for use in Angioimmunoblastic T-cell Lymphoma.