Fast Achievement Of a First Metabolic Complete Remission In a Lung Transtplanted Patient With Multiple Comorbidities and a CD30 Positive Anaplastic Large Cell Post-Transplant Lymphoproliferative Disorder (T-PTLD/ALCL) By Treatment With Brentuximab Vedotin Monotherapy
Authors: Willenbacher Ella , Kreczy Alfons , Uprimny Christian , Bucher Brigitte , Gastl Guenther A. , Willenbacher Wolfgang 
Published: October 2019

Abstract

Introduction
Post-Transplant-Lymphoproliferative Disorders are well known known, but rare complications of solid organ or hematologic stem cell transplantations. Incidence after lung-transplantation [LU-TX] is estimated to be ∼ 4.8% (Kremer et al. 2012). Most cases present as B-cell lymphomas (&gt; 90%) and are EBV-associated. The WHO classification discriminates multiple subtypes (early lesions, monomorphic PTLD, polymorphic PTLD & classical Hodgkin lymphoma type PTLD). Treatment options mirror this histologic diversity and range from reduction of immunosuppressive therapy only , to aggressive polychemotherapy, DLI and second transplants.

Patient history
In May 2001 a left sided single LU-TX was performed for high grade bullous emphysema in a then 50 years old male patient. Several episodes of organ rejection required the use of complex immunosuppressive combination therapies, but long-term pulmonary function was preserved and the patient could be tapered to Tacrolimus and low dose steroids for years. Over the years the patient developed multiple severe comorbidities (Diabetes, renal retention, multiple pulmonary embolic events and peripheral thrombosis, as well as cardiac insuffiency and relapsing episodes of pancreatitis). CIRS-G-severity index was 2.7/4 with an ECOG score of 3. In May 2013 the patient developed B-symptoms, cutaneous lesions and a predominantly inguinal and abdominal lymphadenopathy.

Histology & Staging
A lymph node excision biopsy showed a high grade T-Cell lymphoma (molecular and immunological features are sumarized in Table 1) which could be classified as ALK negative anaplastic large cell lymphoma (ALCL) type PTLD, stage IV BE cutis with additional high risk features (LDH elevation).

Treatment
Because the patient was jugded to be unfit for aggresive polychemotherapy due to multiple comorbidities and his lymphoma was found to be expressing the CD30 antigen strongly and uniformly the anti-CD 30 immunotoxin Brentuximab-Vedotin (BV) was started at 1.8mg/m² every 21 days. B-symptoms disappeared within hours from the first infusion, palpable lymph nodes regressed within 3 weeks, and the patient improved to ECOG 1 in the same period. Furthermore LDH normalized by cycle 2. A PET-CT scan after cycle 3 proved a first complete metabolic remission and the treatment will be continued for 6 cycles. Data on response will be updated at ASH. No clinically relevant toxicities were observed.

Conclusion
To our best knowledge this is the 1st report of the successful use of BV in a case of T-PTLD/ALCL after SLU-TX. As this case illustrates Brentuximab-Vedotin is a highly attractive , low toxicity treatment option in patients unfit to undergo aggressive polychemotherapy and can deliver complete responses with undeniable clinical benefit even in very advanced diease. For the rarity of these diseases the performance of a randomized clinical trial comparing BV to standard treatments seems unlikely for the foreseeable future and clinical decisions on treatment allocation have to be made on a case by case basis. We would recommend to at least collect all cases of BV use in PTLD to improve the respective best available evidence.

Disclosures:
Off Label Use: Brentuximab Vedotin for PTLD treatment.