Fractionated Cyclophosphamide, Vinblastine with Prednisolone and Daily Oral Etoposide Based Treatment of AIDS-Related Plasmablastic Lymphomas (PBL): A Highly Active and Well Tolerated Regimen
Authors: Sengar Manju , Shet Tanuja , Nair Reena , Sridhar Epari , Menon Hari , Gujral Sumeet , Laskar Siddhartha , Alahari Aruna 
Published: October 2019

Abstract
Abstract 2690

Background:
Aggressive biology, tumor re-growth on treatment and poor tolerance to chemotherapy, are the factors responsible for dismal outcomes in patients with AIDS- related PBL. Treatment with CHOP, CHOP-like regimens or more intensive protocols (HyperCVAD, CODOX-M/IVAC) has failed to improve median survival beyond 15 months. To overcome the problems of tumor re-growth secondary to cancer cell resistance and treatment related toxicity, we devised a regimen in which drugs with proven anti-lymphoma activity were given in fractionated and continuous manner. Continuous daily dosing of oral etoposide for 2–3 weeks provides an effective concentration of drug for extended time periods. Anthracyclines were omitted to reduce the incidence of myelosuppression and mucositis. This regimen was tested prospectively to assess the efficacy and tolerability

Methods:
Between August 2007 to February 2011, consecutive patients with untreated AIDS-related PBL and age >18 years were counseled for treatment with the proposed regimen at our center. Diagnosis of PBL required absent or weak expression of CD20, expression of MUM-1 or CD 38 or CD138 to suggest plasma cell differentiation. Paraffin blocks were evaluated for expression of EBER, HHV-8 and Ki-67. All patients who were willing for treatment and follow up and did not have CNS involvement or concurrent infections were enrolled. Anti-retroviral therapy (ART) was started concurrently with chemotherapy if not received before. The 3-weekly regimen included cyclophosphamide 375 mg/m2 and vinblastine 4mg/m2 intravenously on day 1 and 8, oral etoposide 50 mg daily for 2 weeks and prednisolone 40 mg/m2//day for the first week of each cycle. Ten weekly doses of intrathecal methotrexate were given as CNS prophylaxis. Radiation was given to the bulky and extranodal sites. Mid and end of therapy responses were evaluated clinically and radiologically (CT or PET-CT).

Results:
Eighteen patients (males-11, females-7) with median age of 37.5 years (range, 22–51 years) were treated with the above mentioned regimen. Two-thirds of patients were not on ART at diagnosis. Ten patients had tuberculosis as an AIDS-defining illness. Median CD4 count at diagnosis was 175/μL (range 75–407/μL). Significant proportion of patients had adverse prognostic features like B symptoms (9/18), performance status (ECOG) ≥2 (11/18), stage III/IV disease (14/18), bulky disease (15/18), multiple extranodal sites (6/18), raised serum LDH (9/18). Extranodal disease was seen in 17/18 patients commonest being bone followed by anal canal. All except one patient received treatment with chemotherapy (median cycles-6, range 4–8). This patient did not follow up after the initial staging evaluation. Complete responses were seen in 15/17 patients after chemotherapy and 2 patients had partial response. Sixteen patients received radiation. All patients except one had complete response after RT. Patient who continued to have partial response at the end of radiation progressed after 7 months and died. At median follow up of 19 months (range, 3–48 months) both overall survival and event free survival are 87.7%. Median overall survival has not yet been achieved. Treatment was well tolerated with 6 episode of febrile neutropenia which were managed on outpatient basis. One patient was hospitalized for pneumonitis for 7 days. There were no treatment related deaths. On paraffin blocks expression of EBER was seen in 55%. None of them were positive for HHV-8. Six patients had Ki-67 of >90%.

Conclusion:
This is the first reported series from a single center which has shown improved response rates and survival for AIDS related PBL with a novel regimen as compared to available data till date. However the study has limitations of small size and short follow up.

Disclosures:
No relevant conflicts of interest to declare.