R-HCVAD Alternating with R-Methotrexate Cytarabine in Younger Patients (pts) with IH and High-Risk Age Adjusted-IPI DLBCL

The management of pts with untreated, high-risk DLBCL needs improvement. R-HCVAD/R-MTX-ARA-C is a regimen with significant activity in Burkitt's, ALL, and mantle cell lymphomas. The aim of this phase II study is to evaluate the efficacy and safety of R-HCVAD in patients up to 60 years with IH or High risk DLBCL by age adjusted IPI.

Pts with untreated indolent DLBCL with aa-IPI score of 2 or 3 risk were eligible. Treatment was R-HCVAD alternating with R-Methotrexate-cytarabine unless the patient had an effusion that precluded from receiving methotrexate. Prophylactic antibiotics and growth factors were routinely given to pts, and intrathecal prophylaxis were given in patients who were considered to be at high risk for CNS recurrence. Response was assessed every 2 cycles using the International Working Group Response Criteria 2007 incorporating PET scan.

A total of 48 pts received at least one cycle of treatment and were evaluable for toxicity. Forty-five were evluable for response. Pts characteristics are the followings; male 60%, median age 50 (24–60), elevated LDH 92%; stage IV 79%, III 19%, PS>1 69%, AA IPI IH 42%, High 58%. Pts received a median of 6 cycles (1–6). Two patients died after 1^stcycle, 1 due to sepsis, another pulmonary embolism. Another patient refused treatment after the second cycle and died of disease. CR was observed in 83%,PR in 6%, PD 2%. At the moment of this evaluation, with a median follow of 30 months, 35 (73%) are alive in first remission, 2 (4%) died in CR of glioblastoma and anal cancer, 5 (10%) died of disease, 2 are alive with disease, 2 are alive after transplant, and 2 patients died of toxicity.

R-HCVAD/R-MTX-Cytarabine is a very active regimen in DLBCL with high-risk features. We however observed significant hematological toxicities and early death in this study.

Fanale:Genetech: Research Funding. Younes:Seattle Genetics: Research Funding; Allos: Research Funding. Wang:Onyx Pharmaceuticals: Honoraria, Research Funding. Fayad:Roche: Research Funding.