MP versus MPT for previously untreated elderly patients with multiple myeloma: A meta-analysis of 1,682 individual patient data from six randomized clinical trials.

Bringhen

Ludwig

et al. 2011

Blood

314

213

Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-doseintensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes. IntroductionMultiple myeloma (MM) is a malignant disease characterized by uncontrolled plasma tumor cell proliferation, driven by intrinsic chromosomal abnormalities and extrinsic stromal cell support, together with the presence of monoclonal protein in the blood or urine or both. 1,2 Typical clinical presentation at diagnosis includes anemia (commonly presenting as fatigue), skeletal lesions (presenting as bone pain), renal impairment, and hypercalcemia. In Western countries, the annual age-adjusted incidence of MM is 5.6 cases per 100 000 people. The median patient age at diagnosis is ϳ 70 years; only 37% of patients with newly diagnosed (ND) disease are aged Ͻ 65 years, 26% are aged 65-74 years, and 37% are aged Ն 75 years. 3 The annual prevalence of MM in patients aged 65-74 years is ϳ 31 cases per 100 000 people, and it increases to 46 cases per 100 000 people in patients aged Ն 75 years. Furthermore, the number of elderly patients with MM will probably increase because of the improved survival times that are associated with novel agents coupled with the increasing life expectancy of the general population.In recent years, the introduction of novel agents such as thalidomide, lenalidomide, and the proteasome inhibitor bortezomib, which are associated with high-dose therapy and autologous stem cell transplantation in young patients and standard chemotherapy in elderly patients, has changed the management of myeloma and extended overall survival (OS) times. [4][5][6][7] An estimate of the 5-year relative survival of patients with MM in the United States from 1990States from -1992States from to 2002States from -2004 reported a significant survival increase from 29%-35%. More subs...

Section: Mp Versus Combination Melphalan Prednisone and Thalidomidementioning

confidence: 88%

Section: Mp Versus Combination Melphalan Prednisone and Thalidomidementioning

confidence: 99%

Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)

Bringhen

Ludwig

et al. 2011

Blood

314

213

“…A metaanalysis on 1,685 individual patients enrolled in these 6 trials was done and confirmed the superiority of MPT over MP. MPT led to an increase in median PFS and OS of 5.4 months and 6.6 months, respectively (66). Thalidomide therapy was generally well tolerated, even in patients aged 75 years and older (64), although the MPT regimen was associated with a significantly higher incidence of grade 3 to 4 nonhematologic adverse events, including neurologic adverse events, infections, cardiac toxicity, and deepvenous thrombosis.…”

Section: Induction Therapies In the Era Of Novel Agentsmentioning

confidence: 98%

Shifts in the Therapeutic Paradigm for Patients Newly Diagnosed with Multiple Myeloma: Maintenance Therapy and Overall Survival

Clinical Cancer Research

Attal

Roussel

2011

High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard of care for eligible newly diagnosed multiple myeloma (MM) patients. Several randomized studies showed a survival advantage for patients undergoing transplantation, compared with conventional chemotherapy. Introduction of new drugs in this setting has markedly increased survival rates within the last 10 years. Efforts to further improve response rates and survival in those patients are still needed, mainly by increasing the depth of tumor reduction and the duration of response through more effective induction, consolidation, and maintenance therapies. Nevertheless, this approach is currently challenged by the promising results of long-term treatment with novel agents. Recent data suggest that the upfront combination of a proteasome inhibitor plus 1 immunomodulatory compound (IMiD) is highly effective. The combination of bortezomib, thalidomide, and dexamethasone (VTD) has proven to be highly effective as a frontline treatment and is significantly superior to vincristine, doxorubicin, and dexamethasone (VAD) or thalidomide and dexamethasone (Thal-Dex) before and after ASCT with a very manageable toxicity pattern. The most promising 3-drug association might be bortezomib, lenalidomide, and dexamethasone (VRD). Adjunction of a 4th drug has not proven to be more efficient. In patients not eligible for ASCT, the introduction of novel agents has changed the management of multiple myeloma. The combinations of melphalan, prednisone, and thalidomide and of bortezomib, melphalan, and prednisone have shown improved progression-free survival and overall survival in comparison with melphalan and prednisone alone. Melphalan, prednisone, and thalidomide and bortezomib, melphalan, and prednisone are now the new standards of care for elderly patients. Preliminary results also support the role of the combination of melphalan, prednisone, and lenalidomide followed by maintenance therapy with lenalidomide in the treatment of elderly patients. Physicians now have a wider variety of treatment options to tailor the most appropriate and efficacious treatment according to their patients' characteristics.

“…In addition, VEGF seems to be a growth factor for primary human AML cells 9 ; thus, even bevacizumab may represent an agent with both direct and indirect antileukemic effects at least for certain patients.…”

mentioning

confidence: 99%

Balancing act for elderly myeloma

2010

Blood