PS1078 A PHASE II STUDY OF FRACTIONATED CYCLOPHOSPHAMIDE, VINBLASTINE, ORAL ETOPOSIDE AND PREDNISOLONE IN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME RELATED LYMPHOMAS
Authors: Jain H. , Sengar M. , Sridhar E. , Gota V. , Laskar S. 
Published: June 2019

Background:

AIDS‐related lymphomas (ARL) are difficult‐to‐treat, due to the inherent resistance, poor tolerance and risk of opportunistic infections. Dose‐adjusted R‐EPOCH regimen is effective in ARL. The issues with REPOCH include the need for a central line, hospitalization, frequent hospital visits and the cost. These issues are relevant in the developing countries where most of these patients belong to low socio‐economic status and are anti‐retroviral therapy (ART)‐naive. To address these problems, we tested the efficacy of a novel outpatient regimen that includes cyclophosphamide, vinblastine, oral etoposide and prednisolone (CVEP). Fractionation (Cyclophosphamide and Vinblastine) and prolonged administration (Etoposide and Prednisolone), potentially overcome the tumour resistance and reduces toxicities.

Aims:

The primary objective was the complete response. Simon design was used for sample size calculation. The expected response rate was at least 50% and a rate below 30% was considered unacceptable.

Methods:

This single‐centre phase II study, enrolled patients (18 years or above) with de‐novo DLBCL and plasmablastic lymphoma. Patients without CNS involvement and ECOG PS<4 were included. Patients received 6 cycles of CVEP regimen (Intravenous Cyclophosphamide 375 mg/m2 and vinblastine 4 mg/ m2 day1 and 8, Oral Etoposide 50 mg /day for 14 days and prednisolone 40 mg/m2 for 7 days q 21 days) with weekly intrathecal methotrexate for 10 doses. The responses were assessed after 4 and 6 cycles with 18‐FDG PET‐CT. Consolidative radiation was given to the extranodal and bulky sites.

Results:

A total of 42 patients (male:female‐31:11)with a median age of 42 years (range 31–59 years) were enrolled from 2011 to 2016. NHL was the AIDS‐defining illness in 77% of the cases. 57% of the patients’ ART naïve. 25% of patients had CD4 counts <100/cumm (median‐228, range 43–782/cumm). The histology was DLBCL in 60% and Plasmablastic in 40%. Most patients had adverse features‐advanced stage (79%), bulky disease (60%), extranodal sites (80%, >1 extranodal sites in 40%) and raised LDH (65%). Adverse characteristics like hypoalbuminemia and poor PS was seen in 24% and 16% respectively. Median no of 6 cycles (range 1–6) was given. A total of 28/42 patients achieved a complete response at the end of therapy. Consolidative radiation was given to 27 patients. At the median follow up of 34 months (range 1–74 months) the 3‐year overall and progression‐free survivals were 51% and 43% respectively. A total of 212 cycles were administered. Grade 3/4 toxicities (febrile neutropenia, diarrhoea, pneumonia) were seen in less than 5% of cycles. G‐CSF was used in 17% of all the cycles. Treatment‐related complications requiring hospitalization occurred in 19% of the cycles. The median duration of hospitalization was 5 days (range 2–30 days). There were 2 treatment‐related deaths. Two patients died after completion of therapy due to opportunistic infections. The plasma etoposide trough concentration was measured in 9 patients on day 7 and day 14. The mean concentration was 0.21 mg/L on day 7 and 0.28 mg/L on day 14 of therapy indicating adequate cytotoxic concentration.

Summary/Conclusion:

The CVEP regimen appears to be active and well tolerated in DLBCL and plasmablastic lymphomas. The regimen can be easily administered on an out‐patient basis and can overcome the logistic issues associated with infusional therapy.