Management of older patients with multiple myeloma

Gay, Francesca; Palumbo, Antônio

doi:10.1016/j.blre.2010.10.003

Cited by 25 publications

(19 citation statements)

References 51 publications

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“…10 These AEs, particularly thrombocytopenia and neutropenia, are caused by the disease itself, occur more commonly, and are a more serious concern following MM treatment with other drugs, especially in combination with alkylating agents. 35 The hematologic safety profile of carfilzomib, particularly the lack of evidence of cumulative thrombocytopenia and low rates of febrile neutropenia, compares favorably with other MM therapies including pomalidomide 9,36 and bortezomib, 37 providing further evidence of its acceptable safety profile in heavily pretreated patients with MM. In addition, the hematologic AEs reported for carfilzomib were infrequently dose limiting, the Grade 3/4 hematologic AEs were generally reversible, and serious clinical sequelae were rare.…”

Section: Discussionmentioning

confidence: 99%

Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies

Martin²,

et al. 2013

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Carfilzomib, a selective proteasome inhibitor, was approved in 2012 for the treatment of relapsed and refractory multiple myeloma. Safety data for single-agent carfilzomib have been analyzed for 526 patients with advanced multiple myeloma who took part in one of 4 phase II studies (PX-171-003-A0, PX-171-003-A1, PX-171-004, and PX-171-005). Overall analyses of adverse events and treatment modifications are presented, as well as specific analyses of adverse events by organ system. Overall, the most common adverse events of any grade included fatigue (55.5%), anemia (46.8%), and nausea (44.9%). In the grouped analyses, any grade adverse events were reported in 22.1% for any cardiac (7.2% cardiac failure), 69.0% for any respiratory (42.2% dyspnea), and 33.1% for any grouped renal impairment adverse event (24.1% increased serum creatinine). The most common non-hematologic adverse events were generally Grade 1 or 2 in severity, while Grade 3/4 adverse events were primarily hematologic and mostly reversible. There was no evidence of cumulative bone marrow suppression, either neutropenia or thrombocytopenia, and febrile neutropenia occurred infrequently (1.1%). Notably, the incidence of peripheral neuropathy was low overall (13.9%), including patients with baseline peripheral neuropathy (12.7%). Additionally, the incidence of discontinuations or dose reductions attributable to adverse events was low. These data demonstrate that single-agent carfilzomib has an acceptable safety profile in heavily pre-treated patients with relapsed/refractory multiple myeloma. The tolerable safety profile allows for administration of full-dose carfilzomib, both for extended periods and in a wide spectrum of patients with advanced multiple myeloma, including those with pre-existing comorbidities. ABSTRACTpression including thrombocytopenia, and dose-limiting peripheral neuropathy (PN) (up to 30% Grade 1/2 and 7-15% Grade 3/4). The PN often leads to discontinuation, and can be debilitating and occasionally irreversible. [19][20][21] Thalidomide is even more strongly implicated in PN, 22 and a recent analysis of patients with newly diagnosed MM revealed that although thalidomide improved efficacy when added to melphalan-prednisone, it negatively impacted safety. 23 Maintenance therapy, as well as consolidation strategies, with many of these drugs are being investigated as important ways to improve and prolong responses in patients with MM, 24 and these extended treatment periods may draw increased attention to tolerability and cumulative toxicities when considering longterm treatment options.Carfilzomib was initially evaluated in 2 phase I studies 25 and PX-171-002 26) investigating two different dosing schedules: 5 consecutive days of a 14-day cycle and 2 consecutive days/week for 3 weeks of a 28-day cycle). Consecutive day dosing demonstrated promising antitumor activity. However, single-agent carfilzomib administered using the 2 consecutive day dosing schedule (PX-171-002) was better tolerated and was chosen for further exploration in ph...

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Section: Discussionmentioning

confidence: 99%

Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies

Martin²,

et al. 2013

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“…Patients without risk factors should be administered full-dose treatment. 46,79 Recommended starting doses and dose adjustments according to age groups and vulnerability status are presented in Table 4. When a grade 3 or 4 AE occurs during treatment, therapy should be discontinued until the toxicity has resolved, usually by the start of the next cycle, at which point treatment can be restarted at a lower dose (Table 4).…”

Section: Tailored Therapy For the Treatment Of Elderly Patients With MMmentioning

confidence: 99%

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

Palumbo

Bringhen

Ludwig

et al. 2011

Blood

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312

213

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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...

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“…72 When platelet count falls below < 25,000/mm 3 (grade 4 thrombocytopenia) therapy should be withheld until thrombocytopenia resolves to at least grade 2 (platelet count ≥ 50,000/mm 3 ). Therapy could be then reintroduced with appropriate dose reductions of myelotoxic drugs.…”

Section: Thrombocytopeniamentioning

confidence: 99%

Management of older adults with multiple myeloma

Palumbo¹,

Mina²

2013

Blood Reviews

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Two-thirds of patients with multiple myeloma are aged 65 years or more and the prevalence of multiple myeloma in elderly patients is expected to rise in the next future. Patients older than 65 years are usually considered ineligible for transplantation. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, combined with conventional chemotherapy, has radically changed the treatment paradigm of elderly patients and improved outcome. A sequential approach, consisting of an induction regimen associated with a high rate of complete response, followed by consolidation/maintenance therapy, induces a profound cytoreduction and delays relapse, thus improving survival. Novel agents associated with reduced-intensity autologous transplant showed to be safe and effective in fit elderly patients. Patients older than 75 years or vulnerable ones are more susceptible to adverse events that negatively affect treatment adherence and outcome. In this setting, less toxic regimens and appropriate dose reductions should be adopted. Here we provide an overview of novel agent-based treatment strategies for elderly patients with multiple myeloma.

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Management of older patients with multiple myeloma

Cited by 25 publications

References 51 publications

Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies

Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies

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

Management of older adults with multiple myeloma

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