Sylvie Caulet-Maugendre

Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS

BACKGROUNDnThere is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL.nnnPATIENTS AND METHODSnPatients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C.nnnRESULTSnThirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity.nnnCONCLUSIONnThe bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.

Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

Background There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation. Design and Methods Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed. Results The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3–4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3–4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389).

Age‐related Epstein–Barr virus‐associated B‐cell lymphoproliferative disorders in elderly White patients

(Figure 1D). Immunohistochemical reactions performed at a later date on primary and recurrences showed strong diffuse cytokeratin 5, 14 and MNF116 reactivity of spindle cells in all tumours (Figure 2A,B), while luminal cytokeratin 18 was positive only in ductal epithelial structures. In addition, neoplastic spindle cells also showed a positive reaction, although less extensively, for smooth muscle actin and for p63. Oestrogen and progesterone receptors and human epidermal growth factor receptor-2 (HER-2) were negative in the spindlecell component but oestrogen receptors were positive in the ductal epithelial component of recurrent tumours. Although a morphological spectrum of fibromatosislike metaplastic carcinoma of the breast is well recognized and its clinical behaviour mostly agreed-upon, our case deserves recognition for the following reasons: 1. The initial tumour presented as a pure spindle-cell lesion with unusual keloid-like matrix, which is also rarely seen in fibromatosis proper. 2. Wellto moderately differentiated neoplastic ducts and tubules that were not present in the primary appeared in recurrent tumours producing a biphasic morphological appearance. 3. Contrary to previous claims, lymph node metastases in fibromatosis-like metaplastic carcinoma are possible, if only after repeated recurrences, with a glandular ⁄ solid as well as spindle cell component.