The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide – vincristine – doxorubicin – methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis

287

189

Thalidomide, bortezomib, and lenalidomide have recently changed the treatment paradigm of myeloma. In young, newly diagnosed patients, the combination of thalidomide and dexamethasone has been widely used as induction treatment before autologous stem cell transplantation (ASCT). In 2 randomized studies, consolidation or maintenance with low-dose thalidomide has extended both progression-free and overall survival in patients who underwent ASCT at diagnosis. In elderly, newly diagnosed patients, 3 independent randomized studies have reported that the oral combination of melphalan and prednisone plus thalidomide (MPT) is better than the standard melphalan and prednisone (MP). These studies have shown better progression-free survival, and 2 have shown improved overall survival for patients assigned to MPT. In refractory-relapsed disease, combinations including thalidomide with dexamethasone, melphalan, doxorubicin, or cyclophosphamide have been extensively investigated. The risks of side effects are greater when thalidomide is used in combination with other drugs. Thromboembolism and peripheral neuropathy are the major concern. The introduction of anticoagulant prophylaxis has reduced the rate of thromboembolism to less than 10%. Immediate thalidomide dose reduction or discontinuation when paresthesia is complicated by pain or motor deficit has decreased the severity of neuropathy. Future studies will define the most effective or the best sequence of combinations which could improve life expectancy. (Blood. 2008;111:3968-3977)

“…The frequency of DVT was higher in the CTD group (11% vs 4%), but grades 3 to 4 neutropenia (4% vs 60%) and infections (7% vs 26%) were greater in the CVAMP group. 47 …”

Section: Newly Diagnosed MMmentioning

confidence: 99%

Thalidomide for treatment of multiple myeloma: 10 years later

Palumbo

Façon

Sonneveld

et al. 2008

287

189

“…Alternative regimens in younger patients who do not plan to receive a transplantation could use alkylating agents in combinations, such as melphalan, prednisone, and bortezomib or cyclophosphamide, thalidomide, and dexamethasone, 60 either of which could also be considered based on the availability of drugs. Less aggressive treatment with, for example, lenalidomide and low-dose dexamethasone, may be appropriate for patients not requiring a very rapid response to initial therapy and who are at reduced risk of early relapse based on standard-risk clinical features (eg, low ␤-2 microgloblin, low LDH, absence of high-risk genetic features).…”

Section: Patients Not Wishing or Not Suitable For High-dose Melphalanmentioning

confidence: 99%

How I treat multiple myeloma in younger patients

Stewart

Richardson

Miguel

2009

121

Therapeutic options for multiple myeloma (MM) patients have changed quickly in recent years and uncertainty has arisen about optimal approaches to therapy. A reasonable goal of MM treatment in younger "transplant eligible" patients is to initiate therapy with a target goal of durable complete remission, and the anticipated consequence of long-term disease control. To achieve this goal we recommend induction therapy with multiagent combination chemotherapies (usually selected from bortezomib, lenalidomide, thalidomide, cyclophosphamide, and corticosteriods) which when employed together elicit frequent, rapid, and deep responses. We recommend consolidation with high-dose melphalan and autologous stem cell transplantation in the majority of patients willing and able to undergo this procedure and subsequent maintenance therapy, especially in those failing to achieve a complete response or at high risk for early relapse based on prognostic, genetically defined risk factors. Defining genetic risk for early relapse is therefore an important aspect of early diagnostic testing and attention to minimizing expected toxicities once therapy begins is critical in ensuring the efficacy of modern combination therapy approaches. When access to newer drugs is restricted participation in clinical trials should be pursued. (Blood. 2009;114: 5436-5443)

“…, W.M.G., S.E.B., A.J.S., N.N.C., G.C., S.F., J.L.B., H.R., C.R., M.T.D., R.G.O., F.M.R., N.H.R., G.H.J., and J.A.C., manuscript submitted, January 2011). 17 Here we report the results of a large multicenter, randomized study (MRC Myeloma IX) in which we compared the efficacy and safety of an attenuated CTD regimen (CTDa) with that of the previous standard therapy, MP, in patients with NDMM who were ineligible for high-dose therapy and ASCT. The influence of age and cytogenetic profile on survival outcomes after these treatments was also assessed.…”

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation

Morgan

Davies

Gregory

et al. 2011

Self Cite

177

109

As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n ‫؍‬ 426) with melphalan and prednisolone (MP; n ‫؍‬ 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111. (Blood. 2011;118(5):1231-1238)