IVAC With or Without Rituximab for Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas: Real-World Experience in the Modern Era

Part B of the modified Magrath regimen (IVAC) +/- rituximab (R) is recommended as standalone therapy by national guidelines for management of relapsed/refractory Burkitt lymphoma, and is used in other non-Hodgkin lymphomas (NHL). Activity of IVAC in B-cell NHL, particularly with R, and its toxicity remain incompletely described. We reviewed patients with relapsed/refractory B-cell NHL treated with IVAC +/- R between 2004 and 2019 at Memorial Sloan Kettering Cancer Center to assess efficacy and toxicity. Among 54 eligible patients (median 2 prior lines of therapy), 76% had diffuse large B-cell lymphoma; 30% had central nervous system involvement at IVAC initiation. Objective response rate was 48%. At median 22-month follow-up, median progression-free and overall survival were 3.1 months and 4.9 months, respectively. Grade ≥ 3 anemia (93%), neutropenia (94%), and thrombocytopenia (100%; all grade 4) were common. Febrile neutropenia occurred in 65% and did not appear to be influenced by use of antimicrobial or granulocyte colony stimulating factor prophylaxis. Mortality was attributed to treatment in 19% of evaluable patients. The clinical efficacy and utility of IVAC +/- R remain unclear. However, its profound hematologic toxicity and life-threatening complications despite prophylactic measures warrant careful consideration of alternatives. IVAC +/- rituximab (R) is used as standalone therapy in relapsed/refractory non-Hodgkin lymphomas (NHL) despite a paucity of data. We report a retrospective cohort of 54 patients with relapsed/refractory NHL treated with IVAC +/- R. Objective response rate was 48%; severe toxicity and treatment-related mortality were noted. While IVAC's clinical activity is unclear, profound hematologic toxicity and complications despite preventive measures require careful consideration of alternatives.