Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial

• Published in: Blood Vol. 111; no. 2; pp. 537 - 543
• Main Authors: Vellenga, Edo, van Putten, Wim L.J., van 't Veer, Mars B., Zijlstra, Josée M., Fibbe, Willem E., van Oers, Marinus H.J., Verdonck, Leo F., Wijermans, Pierre W., van Imhoff, Gustaaf W., Lugtenburg, Pieternella J., Huijgens, Peter C.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.01.2008; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biological and medical sciences; Cisplatin - administration & dosage; Cytarabine - administration & dosage; Dexamethasone - administration & dosage; Disease-Free Survival; Etoposide - administration & dosage; Female; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Ifosfamide - administration & dosage; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - mortality; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell - therapy; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Prospective Studies; Recurrence; Remission Induction; Rituximab; Stem Cell Transplantation; Survival Rate; Transplantation, Autologous; Antineoplastic agent; Relapse; Hematology; Rituximab; Malignant hemopathy; Monoclonal antibody; Non Hodgkin lymphoma; Prospective; Randomization; Treatment; Lymphoproliferative syndrome; Immunotherapy; Clinical trial; Cancer; High malignancy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-08-108415

We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+ non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in complete remission (CR) and partial remission (PR) after 2 chemotherapy courses were eligible for autologous stem-cell transplantation. After the second chemotherapy cycle, 75% of the patients in the R-DHAP arm had responsive disease (CR or PR) versus 54% in the DHAP arm (P = .01). With a median follow-up of 24 months, there was a significant difference in failure-free survival (FFS24; 50% vs 24% vs, P < .001), and progression free survival (PFS24; 52% vs 31% P < .002) in favor of the R-DHAP arm. Cox-regression analysis demonstrated a significant effect of rituximab treatment on FFS24 (HR 0.41, 95% confidence interval [CI] 0.29-0.57 versus 0.51, 95% CI 0.37-0.70) and overall-survival (OS24: HR 0.60 [0.41-0.89] vs 0.76 [0.52-1.10]) when adjusted for time since upfront treatment, age, World Health Organization performance status, and secondary age-adjusted international prognostic index. These results demonstrate improved FFS and PFS for relapsed aggressive B-cell NHL if rituximab is added to the re-induction chemotherapy regimen.