Long-Term Follow-Up of R-CHOP With Bevacizumab as Initial Therapy for Mantle Cell Lymphoma: Clinical and Correlative Results |
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| Affiliation: | 1. Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY;2. Division of Hematology and Medical Oncology, Rush University Medical Center, Chicago, IL;3. Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY;1. Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan;2. Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan;3. Research Center for Cancer Stem Cell, Tokai University School of Medicine, Isehara, Kanagawa, Japan;4. Teaching and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa, Japan;5. Division of Hematology, Ebina General Hospital, Ebina, Kanagawa, Japan;1. Research Center for Cancer Stem Cell, Tokai University School of Medicine, Isehara, Kanagawa, Japan;2. Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan;3. Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan;4. Support Center for Medical Research and Education, Tokai University School of Medicine, Isehara, Kanagawa, Japan;5. Medical Research Institute, Tokai University, Isehara, Kanagawa, Japan;1. Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA;2. Center for Neuro-Oncology, BIDMC, Boston, MA;3. Swedish Neuroscience Institute, Ben and Catherine Ivy Center, Seattle, WA;4. Department of Radiology, Massachusetts General Hospital, Boston, MA;5. Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA;1. Clinical Medicine Post Graduation''s Program – Medicine College, Rio de Janeiro''s Federal University (UFRJ), Rio de Janeiro, Brazil;2. Cytogenetics Department, Bone Marrow Transplantation Unit (CEMO), National Cancer Institute (INCA), Rio de Janeiro, Brazil;3. Post Graduation''s Oncology Program – National Cancer Institute (INCA), Rio de Janeiro, Brazil;4. Biophysics and Biometry Department, Roberto Alcântara Gomes Biology Institute, Rio de Janeiro''s State University (UERJ), Rio de Janeiro, Brazil;5. Oncology Service, Santa Casa de Misericórdia de Itabuna, Bahia, Brazil;6. Department of Oncology and International Outreach Program, St Jude Children''s Research Hospital, Memphis, TN;7. Martagão Gesteira Institute of Pediatrics and Child Development, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil |
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| Abstract: | BackgroundEmerging evidence indicates that MCL has increased angiogenesis within the tumor microenvironment. We initiated a phase II trial to determine if the addition of bevacizumab to the standard R-CHOP regimen could enhance antitumor effects in patients with previously untreated MCL.Patients and MethodsEleven patients with previously untreated MCL received bevacizumab at 15 mg/kg on day 1, and standard CHOP-21 (CHOP given every 21 days per cycle) with rituximab (375 mg/m2 per cycle) on day 3 of each cycle for a total of 6 cycles. Planned study end points included safety and efficacy assessment, and exploratory analysis of angiogenic profiles. The study was suspended in August of 2010 based on safety findings in DLBCL (diffuse large B-cell lymphoma) of increased cardiovascular events with the regimen.ResultsBeyond the standard R-CHOP safety profile, Grade 3 left ventricular dysfunction developed in 2 patients (18%), Grade 1/2 hypertension, proteinuria, and bleeding each developed in 1 patient (9%). The overall response rate was 82% with 36% complete response (CR)/complete response unconfirmed (CRu). The median progression-free survival (n = 11) was 18 months (95% confidence interval, 3-not reached), and 3-year overall survival rate was 82%. Correlative studies showed increased vascular endothelial growth factor receptor 1 expression in tumor cells at baseline, and elevated levels of plasma vascular endothelial growth factor (VEGF) throughout treatment.ConclusionThe addition of bevacizumab to the standard R-CHOP regimen did not appear to significantly improve efficacy beyond that observed from previous studies using R-CHOP alone. Therapeutic strategies that provide sustained inhibition on VEGF-related and VEGF-independent targets within the tumor microenvironment might further improve antiangiogenic effects and warrant further exploration in MCL. |
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| Keywords: | Angiogenesis Anti-VEGF Chemotherapy Mantle cell lymphoma Tumor microenvironment |
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