Subject(s)
B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Interleukin-10/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/etiology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Polymorphism, Genetic , Receptors, IgG/genetics , Rituximab/therapeutic use , Antibody-Dependent Cell Cytotoxicity , B-Lymphocytes/pathology , Female , Humans , Male , Rituximab/administration & dosage , Treatment OutcomeABSTRACT
Emergence of new agents has deeply modified treatment options and the role of chlorambucil (CLB) in B-cell malignancies. We conducted a systematic review of prospective, randomized, controlled trials (RCTs) investigating the benefits and harms of CLB used alone or in combination with other treatment in patients suffering from chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) or Waldenström macroglobulinemia (WM). For CLL, review of the nine RCTs showed that the main advantage of CLB is its low toxicity in comparison with purine nucleoside analogs like fludarabine in either CLL or NHL. In CLL, the major disadvantage is the very low rate of complete response, except when combining an anti-CD20 antibody. For B-cell lymphoma and WM, six RCTs were summarized. Results according to the usual criteria are presented and the role of CLB, used mostly in combination with an anti-CD20 antibody, is discussed for each indication, in particular for unfit patients.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Chlorambucil/therapeutic use , Leukemia, B-Cell/drug therapy , Lymphoma, B-Cell/drug therapy , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chlorambucil/administration & dosage , Chlorambucil/adverse effects , Drug Administration Schedule , Humans , Leukemia, B-Cell/diagnosis , Leukemia, B-Cell/mortality , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/mortality , Treatment OutcomeABSTRACT
BACKGROUND: There 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. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-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. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.