Abstract ID:  #427 Case Report: A Challenging Case of Managing Relapsed & Refractory Hodgkin's Lymphoma Prashanth Hari Dass, Michael B. Jameson, and Elliot M. Epner Waikato Hospital, Hamilton, New Zealand Correspondence: email pranava108@hotmail.com Introduction Relapse 34 months later… Follow up She represented with right chest wall pain & nocturnal wheeze. Relapse confirmed on CT (Image 3) & biopsy. 3 cycles of IGEV (Ifosfamide, Gemcitabine & Vinorelbine) chemotherapy followed by successful harvest of peripheral blood haemopoietic stem cells. PET-CT scan showed HL progression (Image 4). CT 3 months post-autograft showed resolution of lymphadenopathy, minor residual lung consolidation & pleural thickening (Image 7). CXR 15 months post autograft was unremarkable. Hodgkin's Lymphoma (HL) : An uncommon malignant disease originating predominantly from B lymphocytes More common in western countries compared to Asia. 1 Although largely curable, 33% of patients subsequently relapse. Half of these patients are refractory to salvage treatment.2 Image 3 PET CT: Relapse at 34 months Image 4 PET CT: Progression post-IGEV Case Report History & Examination 19 year-old HIV-negative female 4 month history of enlarging cervical lymphadenopathy, night sweats & weight loss Investigations CT scan: large anterior mediastinal mass & bilateral supraclavicular lymphadenopathy (Image 1) – unfavourable Stage IIB. Histology: Grade 2 nodular sclerosing HL syncytial variant. Reed-Sternberg cells stained positive to CD30, Fascin, CD15, EBER & CD20(focally). PAX-5 was negative. International Prognostic Score 0. Treatment 6 cycles of ABVD chemotherapy (Doxorubicin, Vinblastine, Dacarbazine & Bleomycin) with Filgrastim. PET-CT scan after 2 cycles ABVD showed complete metabolic response (Image 2). She then received involved nodal radiation, 30.6Gy in 17 Fractions. Image 7 CT scan 3 months post-autograft – complete remission Discussion Brentuximab vedotin x 2 cycles failed to induce remission in our patient. The addition of epigenetic therapy to a third cycle produced a dramatic response. Cladribine, an adenosine deaminase inhibitor is efficacious in many haematological malignancies. 3 The addition of Valproate (Histone Deacytelase inhibitor) to Cladribine is synergistic.4 Managing Refractory HL Image 5 CXR after 1 cycle of ESHAP: No response Image 6 CXR - dramatic reduction of hilar mass from 11cm to 6.5cm post Brentuximab, Cladribine & Valproate 1 cycle of ESHAP (Etoposide, Methylprednisolone, Cytarabine & Cisplatin) given while awaiting funding for Brentuximab Vedontin, but no response on CXR (Image 5). She then received 2 cycles of Brentuximab vedotin (1.8mg/kg). PET-CT scan showed stable pulmonary mass; FDG uptake reduced but still moderate. In view of refractory disease, cycle 3 Brentuximab given with IV Cladribine 5mg/m2 Day 1 & Sodium Valproate 500mg orally three times per day. This was well tolerated. CXR after this cycle showed dramatic reduction of the hilar mass (Image 6). This was followed by high-dose BEAM chemotherapy & autologous peripheral blood stem cell transplant. Conclusions This is a fascinating case of refractory HL that achieved complete response with the addition of epigenetic therapy to brentuximab vedotin. We propose a prospective trial to evaluate its efficacy and safety in larger subsets of patients. Image 1 CT at diagnosis Image 2 PET-CT post 2 cycles ABVD References Z Mozaheb. Epidemiology of Hodgkin’s Lymphoma. Health 5 (2013) 17-22. http://file.scirp.org/pdf/Health_2013052717023178.pdf F. Montanari. & C. Diefenbach. Relapsed Hodgkin Lymphoma: Management StrategiesCurr Hematol Malig Rep. 2014 September ; 9(3): 284–293. doi:10.1007/s11899-014-0220-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909353/pdf/nihms606560.pdf S. Spurgeon, M. Yu, J. D. Phillips, E. M. Epner. CLADRIBINE: NOT JUST ANOTHER PURINE ANALOGUE? Expert Opin Investig Drugs 2009 Aug;18(8):1169-81 A. B. Bouzar, M. Boxus, J Defoiche et al. Valproate synergizes with purine nucleoside analogues to induce apoptosis of B-chronic lymphocytic leukaemia cells. British Journal of Haematology. 144. 41-52. 2008