The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission.
We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression.
Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005).
R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).
"Overall responses (complete and partial remissions combined) of approximately 85% can be obtained. A complete remission (CR), no signs of disease left on computed tomography scan and other restaging procedures, is achieved in 30%–40% of patients.18,31 Relapse or progression is common after 2–3 years.18 "
[Show abstract][Hide abstract] ABSTRACT: Mantle cell lymphoma is a relatively rare B-cell lymphoma with a specific genetic lesion and a typical immunophenotypic profile. The median age is 65 years. There is no curative treatment, except allogeneic stem cell transplantation for a selected group of patients. For the majority of patients, especially the elderly, the aim of therapy should therefore be a long progression-free survival. Age and comorbidity may hamper the use of the most active treatment regimen, such as high dose cytarabine and autologous stem cell transplantation. Therefore, it is a challenge to select the most appropriate therapy for an elderly patient. Studies specifically designed for elderly patients are rare. A recently performed large randomized study for elderly patients, however, has shown that R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed by maintenance rituximab can result in a long progression-free survival. For patients too frail for R-CHOP chemotherapy, a treatment should be offered that benefits the patient in reducing the symptoms of the disease without causing too many side effects. Progression or relapse will occur in all patients sooner or later. Second-line treatment should again be carefully selected. Several options are mentioned. New drugs are being developed, and new combinations are investigated. Further improvement in the outcome of patients with mantle cell lymphoma is expected. Participation in well-designed clinical trials, also by elderly patients, is important to find the real benefit that can be achieved, and to get information on the tolerability of these treatments in this age group.
[Show abstract][Hide abstract] ABSTRACT: The role of autologous hematopoietic cell transplantation (auto-HCT) in the management of indolent non-Hodgkin lymphomas (NHL) is shrouded in controversy. The outcomes of conventional therapies for many indolent lymphoma subtypes have dramatically improved over the last several years with the use of monoclonal antibodies, maintenance therapy programs and with the incorporation of radio-immunoconjugates. These significant advances in the armamentarium of lymphoma therapeutics warrant reappraisal of the current role of auto-HCT in the treatment algorithm of indolent NHL. Prospective randomized studies comparing contemporary chemoimmunotherapies against auto-HCT are lacking, leading to significant debate about the role and timing of auto-HCT for indolent NHL in the modern era. Although autografting for follicular lymphoma (FL) in first remission has been largely abandoned, it remains a useful modality for relapsed disease, especially for the subgroup of patients who are not candidates for allogeneic transplantation with a curative intent. Auto-HCT can provide durable disease control in chemosensitive transformed FL and mantle cell lymphoma (MCL) in first remission, with relatively low toxicity, and remains appropriate in chemoimmunotherapy era. Contemporary data are also reviewed to clarify the often underutilized role of autografting in relapsed MCL and other less frequent indolent NHL histologies. The biological basis of the increased risks of second malignancies with auto-HCT are reviewed to identify strategies designed to mitigate this risk by, for example, avoiding exposure to genotoxic agents, planning early stem cell collection/cryopreservation and minimizing the use of TBI with transplant conditioning, and so on. Genetic testing able to identify patients at high risk of therapy-related complications and novel post-transplant immune therapies with the potential of transforming autografting in indolent NHL from a remission-extending therapy to a curative modality are discussed to examine the possibly expanding role of auto-HCT for lymphoid malignancies in the coming years.
Bone Marrow Transplantation 09/2012; 48(8):1013-1021. DOI:10.1038/bmt.2012.182 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, Provenge(®)) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond to DC-based anticancer vaccines. This knowledge may indeed lead to personalized combination strategies that would extend the benefit of DC-based immunotherapy to a larger patient population. In addition, widespread enthusiasm has been generated by the results of the first clinical trials based on in vivo DC targeting, an approach that holds great promises for the future of DC-based immunotherapy. In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating DC-based interventions for cancer therapy.
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