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Primary Effusion Lymphoma in elderly Patient Effectively Treated by Lenalidomide
Abstracts Lymphoma
501 Primary Effusion Lymphoma in elderly Patient Effectively Treated by Lenalidomide
Ahmad Antar,1 Hiba El Hajj,1 Mark Jabbour,2 Ibrahim Khalifeh,2 Fadi EL-Merhi,3 Rami Mahfouz,2 Ali Bazarbachi1 1
Department of Internal Medicine, Division of Hematology and Oncology, American University of Beirut Medical Center, Beirut, Lebanon; 2Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon;
for CD38 while negative for CD138 and CD16/56. The result was consistent with Primary effusion lymphoma. Moreover a review of pathology of the previous abdominal cyst was consistent with the same disease. Human Herpes Virus abs (type 8, IgG) was positive. HIV 1 and 2 Abs and P24 were negative. The patient was started on lenalidomide 25 mg po daily for 21 days every 28 days for each cycle. He had a significant improvement of shortness of breath after the first cycle. CT of Chest after eight cycles of treatment showed significant decrease in the right pleural effusion with complete resolution of the left one. He has been on lenalidomide for 1 year now without any symptoms or evidence of disease progression. To the best of our knowledge, our case is the first reported case of PEL that showed almost complete remission by treatment with lenalidomide with a 1 year follow up till now. Our findings warrant further evaluation in the context of prospective clinical studies.
3
Department of Radiology, American University of Beirut Medical
Center, Beirut, Lebanon
502
Primary effusion lymphoma (PEL) is a rare and aggressive subset of Non-Hodgkin B cell lymphoma. It occurs mainly in HIV-positive patients and less frequently in other groups such as elderly patients and organ transplantation recipients. PEL predominantly develops in serous cavities (pleural, pericardial or abdominal cavities), usually in the absence of an obvious tumour mass or organomegaly, and it is caused by Kaposi sarcoma-associated herpesvirus/human herpes virus8(KSHV/HHV-8). PEL tumor cells are latently infected by KSHV/ HHV-8, it displays constitutive activity of many signaling pathways in growth and survival, including the NF-kB, JAK/STAT and PI3K/Akt pathways. PEL is generally resistant to chemotherapy and carries a very poor prognosis with a median survival of around 6 months. Given its rarity, there are very few observational series of patients with PEL, and very few prospective trials testing chemotherapy, anti-viral therapy or targeted therpay. Therefore, there is no clear standard of care established in the treatment of PEL. The antitumor effect of proteasome inhibitors via inhibition of the NF-kB, which is critical for PEL cell survival, has been tested only in few preclinical mouse models and very few case reports. Lenalidomide, which possesses pleiotropic properties, belongs to the second generation of immunomodulatory drugs. It effectively downregulates the NF-kB pathway. Lenalidomide has never been studied in PEL (neither in preclinical, nor in clinical trials or case reports). We report the case of a 77-year-old male patient who presented with a two-month history of increasing in abdominal girth. A workup was started by a CT scan of abdomen and pelvis that showed a huge cystic peritoneal mass sizing up to 30-35 cm in greatest dimension. He underwent a surgical resection of the cystic lesion that turned out to be a chronically inflamed fibromembranous adipose tissue. Two months later, he was admitted to the hospital for severe dyspnea, CT scan of the chest and PET scan were performed and revealed bilateral pleural effusion more severe in the right side, without evidence of abnormal metabolic uptake. Pleural biopsy and fluid were sent for analysis. Cytopathology revealed a clone of malignant lymphoid cells with high N/C ratio, multiple nucleoli and frequent mitosis. Immunohistochemically, the cells are positive for CD38 and EMA only, and negative for CD45, CD20, CD3, CD43, PAX-5, CD34, CD68, CD117, CD30, TdT, myeloperoxidase, S-100 and CKAE1/3. Flow cytometry revealed a suspicious clone of cells positive
Efficacy, Safety and Responder Subanalysis of Lenalidomide in Heavily Pretreated, Relapsed/Refractory Patients With Mantle Cell Lymphoma Post-Bortezomib: Phase II MCL-001 “EMERGE” Study
Andre Goy,1 Michael E. Williams,2 Sevgi Kalayoglu Besisik,3 Johannes Drach,4 Radhakrishnan Ramchandren,5 Lei Zhang,6 Sherri Cicero,6 Tommy Fu,6 Thomas Witzig7 1
John Theurer Cancer Center at HUMC, Hackensack, NJ; 2University
of Virginia Health System, Charlottesville, VA; 3Istanbul University Faculty of Medicine, Istanbul, Turkey; 4Medical University of Vienna, Oncology, Austria; 5Karmanos Cancer Institute, Detroit, MI; 6Celgene Corporation, Summit, NJ; 7Mayo Clinic, Rochester, MN
Context: Limited treatments are available for patients with relapsed/refractory mantle cell lymphoma (MCL) who progress after or are refractory to bortezomib. The oral non-chemo immunomodulator lenalidomide demonstrates clinical activity in multiple phase II studies of aggressive NHL, including MCL. Objective: To examine the efficacy and safety of lenalidomide in heavily pretreated MCL patients post-bortezomib; additional analyses were performed on responders. Study Design: Phase II global, multicenter MCL001 “EMERGE” study of lenalidomide 25 mg/day PO days 1-21 every 28 days until progression/intolerability (1/2009-7/2012). Primary endpoints were ORR and DOR by independent central review. Patients: Patients received prior rituximab, cyclophosphamide, and anthracycline (or mitoxantrone) and were relapsed/progressed (<12 months) or refractory (2 cycles) to bortezomib. Results: 134 intent-to-treat patients with a median age of 67 years and advanced MCL (93% stage III-IV) were enrolled. Patients were heavily pretreated with a median number of 4 prior therapies (range, 2-10), 78% 3 prior chemotherapy regimens, and 55% refractory to last therapy. The ORR was 28% (7.5% CR/CRu) and median DOR was 16.6 months (95% CI, 7.7-26.7) at a median
Clinical Lymphoma, Myeloma & Leukemia September 2014
- S141
501 Primary Effusion Lymphoma in elderly Patient Effectively Treated by Lenalidomide
Ahmad Antar,1 Hiba El Hajj,1 Mark Jabbour,2 Ibrahim Khalifeh,2 Fadi EL-Merhi,3 Rami Mahfouz,2 Ali Bazarbachi1 1
Department of Internal Medicine, Division of Hematology and Oncology, American University of Beirut Medical Center, Beirut, Lebanon; 2Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon;
for CD38 while negative for CD138 and CD16/56. The result was consistent with Primary effusion lymphoma. Moreover a review of pathology of the previous abdominal cyst was consistent with the same disease. Human Herpes Virus abs (type 8, IgG) was positive. HIV 1 and 2 Abs and P24 were negative. The patient was started on lenalidomide 25 mg po daily for 21 days every 28 days for each cycle. He had a significant improvement of shortness of breath after the first cycle. CT of Chest after eight cycles of treatment showed significant decrease in the right pleural effusion with complete resolution of the left one. He has been on lenalidomide for 1 year now without any symptoms or evidence of disease progression. To the best of our knowledge, our case is the first reported case of PEL that showed almost complete remission by treatment with lenalidomide with a 1 year follow up till now. Our findings warrant further evaluation in the context of prospective clinical studies.
3
Department of Radiology, American University of Beirut Medical
Center, Beirut, Lebanon
502
Primary effusion lymphoma (PEL) is a rare and aggressive subset of Non-Hodgkin B cell lymphoma. It occurs mainly in HIV-positive patients and less frequently in other groups such as elderly patients and organ transplantation recipients. PEL predominantly develops in serous cavities (pleural, pericardial or abdominal cavities), usually in the absence of an obvious tumour mass or organomegaly, and it is caused by Kaposi sarcoma-associated herpesvirus/human herpes virus8(KSHV/HHV-8). PEL tumor cells are latently infected by KSHV/ HHV-8, it displays constitutive activity of many signaling pathways in growth and survival, including the NF-kB, JAK/STAT and PI3K/Akt pathways. PEL is generally resistant to chemotherapy and carries a very poor prognosis with a median survival of around 6 months. Given its rarity, there are very few observational series of patients with PEL, and very few prospective trials testing chemotherapy, anti-viral therapy or targeted therpay. Therefore, there is no clear standard of care established in the treatment of PEL. The antitumor effect of proteasome inhibitors via inhibition of the NF-kB, which is critical for PEL cell survival, has been tested only in few preclinical mouse models and very few case reports. Lenalidomide, which possesses pleiotropic properties, belongs to the second generation of immunomodulatory drugs. It effectively downregulates the NF-kB pathway. Lenalidomide has never been studied in PEL (neither in preclinical, nor in clinical trials or case reports). We report the case of a 77-year-old male patient who presented with a two-month history of increasing in abdominal girth. A workup was started by a CT scan of abdomen and pelvis that showed a huge cystic peritoneal mass sizing up to 30-35 cm in greatest dimension. He underwent a surgical resection of the cystic lesion that turned out to be a chronically inflamed fibromembranous adipose tissue. Two months later, he was admitted to the hospital for severe dyspnea, CT scan of the chest and PET scan were performed and revealed bilateral pleural effusion more severe in the right side, without evidence of abnormal metabolic uptake. Pleural biopsy and fluid were sent for analysis. Cytopathology revealed a clone of malignant lymphoid cells with high N/C ratio, multiple nucleoli and frequent mitosis. Immunohistochemically, the cells are positive for CD38 and EMA only, and negative for CD45, CD20, CD3, CD43, PAX-5, CD34, CD68, CD117, CD30, TdT, myeloperoxidase, S-100 and CKAE1/3. Flow cytometry revealed a suspicious clone of cells positive
Efficacy, Safety and Responder Subanalysis of Lenalidomide in Heavily Pretreated, Relapsed/Refractory Patients With Mantle Cell Lymphoma Post-Bortezomib: Phase II MCL-001 “EMERGE” Study
Andre Goy,1 Michael E. Williams,2 Sevgi Kalayoglu Besisik,3 Johannes Drach,4 Radhakrishnan Ramchandren,5 Lei Zhang,6 Sherri Cicero,6 Tommy Fu,6 Thomas Witzig7 1
John Theurer Cancer Center at HUMC, Hackensack, NJ; 2University
of Virginia Health System, Charlottesville, VA; 3Istanbul University Faculty of Medicine, Istanbul, Turkey; 4Medical University of Vienna, Oncology, Austria; 5Karmanos Cancer Institute, Detroit, MI; 6Celgene Corporation, Summit, NJ; 7Mayo Clinic, Rochester, MN
Context: Limited treatments are available for patients with relapsed/refractory mantle cell lymphoma (MCL) who progress after or are refractory to bortezomib. The oral non-chemo immunomodulator lenalidomide demonstrates clinical activity in multiple phase II studies of aggressive NHL, including MCL. Objective: To examine the efficacy and safety of lenalidomide in heavily pretreated MCL patients post-bortezomib; additional analyses were performed on responders. Study Design: Phase II global, multicenter MCL001 “EMERGE” study of lenalidomide 25 mg/day PO days 1-21 every 28 days until progression/intolerability (1/2009-7/2012). Primary endpoints were ORR and DOR by independent central review. Patients: Patients received prior rituximab, cyclophosphamide, and anthracycline (or mitoxantrone) and were relapsed/progressed (<12 months) or refractory (2 cycles) to bortezomib. Results: 134 intent-to-treat patients with a median age of 67 years and advanced MCL (93% stage III-IV) were enrolled. Patients were heavily pretreated with a median number of 4 prior therapies (range, 2-10), 78% 3 prior chemotherapy regimens, and 55% refractory to last therapy. The ORR was 28% (7.5% CR/CRu) and median DOR was 16.6 months (95% CI, 7.7-26.7) at a median
Clinical Lymphoma, Myeloma & Leukemia September 2014
- S141