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Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma
Author(s) -
Ruan Jia,
Martin Peter,
Coleman Morton,
Furman Richard R.,
Cheung Ken,
Faye Adam,
Elstrom Rebecca,
Lachs Mark,
Hajjar Katherine A.,
Leonard John P.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25055
Subject(s) - medicine , mantle cell lymphoma , rituximab , thalidomide , gastroenterology , regimen , international prognostic index , procarbazine , cyclophosphamide , surgery , prednisone , oncology , vincristine , lymphoma , chemotherapy , multiple myeloma
BACKGROUND: Targeting the tumor microenvironment and angiogenesis is a novel lymphoma therapeutic strategy. The authors report safety, activity, and angiogenic profiling results with the rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide (RT‐PEPC) regimen in patients with recurrent mantle cell lymphoma (MCL). METHODS: RT‐PEPC included induction (Months 1‐3) of rituximab 4 times weekly, daily thalidomide (50 mg), and PEPC followed by maintenance thalidomide (100 mg), oral PEPC titrated to the neutrophil count, and rituximab every 4 months. Endpoints included safety, efficacy, quality of life (QoL), and translational studies, including tumor angiogenic phenotyping, plasma vascular endothelial growth factor (VEGF), and circulating endothelial cells. RESULTS: Twenty‐five patients were enrolled, and 22 were evaluable. The median age was 68 years (range, 52‐81 years), 24 patients (96%) had stage III or IV disease, 18 patients (72%) had an International Prognostic Index (IPI) score of 3 to 5, and 20 patients (80%) had high‐risk Mantle Cell International Prognostic Index (MIPI) scores. Patients had received a median of 2 previous therapies (range, 1‐7 previous therapies), and 15 patients (60%) had progressed on bortezomib. At a median follow‐up of 38 months, the overall response rate was 73% (complete response [CR]/unconfirmed CR rate, 32%; partial response [PR] rate, 41%; n = 22 patients), and the median progression‐free survival was 10 months. Four CRs were ongoing (≥6 months, ≥31 months, ≥48 months, and ≥50 months). Toxicities included grade 1 and 2 fatigue, rash, neuropathy, and cytopenias, including grade 1 and 2 thrombocytopenia (64%) and grade 3 and 4 neutropenia (64%). Two thromboses and 5 episodes of grade 3 or 4 infections occurred. QoL was maintained or improved. Correlative studies demonstrated tumor autocrine angiogenic loop (expression of VEGF A and VEGF receptor 1) and heightened angiogenesis and lymphangiogenesis in stroma. Plasma VEGF levels and circulating endothelial cells trended down with treatment. CONCLUSIONS: RT‐PEPC had significant and durable activity in MCL with manageable toxicity and maintained QoL. Novel, low‐intensity approaches warrant further evaluation, potentially as initial therapy in elderly patients. Cancer 2010. © 2010 American Cancer Society.