Interferon plus Glucocorticoids as Intensified Maintenance Therapy Prolongs Tumor Control in Relapsed Myeloma

Palumbo, Antônio; Boccadoro, Mario; Garino, Lucia A.; Gallone, Giovanni; Frieri, R; Pileri, Alessandro

doi:10.1159/000204379

Cited by 14 publications

(7 citation statements)

References 18 publications

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“…31 Two recent studies suggested that the combination of interferon and glucocorticoids were effective as maintenance therapy for myeloma patients. 19,20 Since maintenance interferon does not improve outcome, this benefit may be observed with the use of glucocorticoids alone. Although pulse dexamethasone produced a similar outcome to 3-times-a-week interferon maintenance therapy among patients responding to MD induction therapy, 21 the type and length of induction therapy (melphalan-containing compared with VAD-like regimens) and the type, dose, and schedule of steroids may be critical to their efficacy during maintenance therapy.…”

Section: Discussionmentioning

confidence: 99%

“…[14][15][16][17][18] For patients either responding or showing stable disease following conventional chemotherapy, a single-arm study demonstrated that maintenance therapy with oral prednisone (50 mg 3 times per week) and interferon resulted in a long duration of remission and overall survival. 19 In a Southwest Oncology Group (SWOG) study, 89 patients responding to induction vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy were randomized to receive maintenance therapy with either maintenance prednisone (50 mg 3 times per week with interferon or interferon alone). 20 Progression-free survival was increased from 9 to 19 months for patients given the combination compared with patients given interferon alone.…”

Section: Introductionmentioning

confidence: 99%

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Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients

Berenson

Crowley

Grogan

et al. 2002

Blood

230

122

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The role of maintenance therapy in multiple myeloma is controversial. Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids, compared with interferon alone. The role of glucocorticoids alone as maintenance therapy has not been previously addressed. We compared alternate-day, oral prednisone at 2 different dose levels (10 mg versus 50 mg) for remission maintenance among previously untreated myeloma patients following a response to induction with standard-dose vincristine, doxorubicin, and dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q). There were 250 eligible patients registered on Southwest Oncology Group study 9210 and randomized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at least a 25% tumor reduction following induction therapy who were randomized to either physiologic (10 mg) or pharmacologic (50 mg) doses of alternate-day, oral prednisone until disease progression. At the time of study entry, patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms randomized to maintenance therapy. After a median follow-up of 53 months, there was no difference in either progression-free or overall survival between the 2 induction regimens. However, from the time of maintenance randomization, both progression-free (14 versus 5 months; P ‫؍‬ .003) and overall survival (37 versus 26 months; P ‫؍‬ .05) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone. There was no difference in treatment-related adverse events between the groups. Thus, 50 mg, oral, alternateday prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy. (Blood. 2002;99:3163-3168)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients

Berenson

Crowley

Grogan

et al. 2002

Blood

230

122

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“…Two studies have shown encouraging results with a combination of IFN-a and glucocorticoids given as maintenance therapy (84,85). A recently published SWOG trial suggests that 50 mg alternate-day prednisone could improve survival in patients responding to induction chemotherapy (86).…”

Section: Maintenance Therapymentioning

confidence: 99%

Multiple Myeloma

Harousseau¹,

Shaughnessy²,

Richardson³

2004

Hematology

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High-dose therapy with stem cell transplantation (SCT) and novel targeted therapies (thalidomide, its more potent analogues, and bortezomib) represent two approaches for overcoming resistance of multiple myeloma (MM) cells to conventional therapies. While it is now clear that dose-intensification improves the outcome in younger patients, long-term remissions are obtained in a minority of patients. Therefore, the impact of novel agents as part of front-line therapy is the objective of ongoing trials. Gene expression profiling (GEP) will help to improve the management of MM not only by identifying prognostic subgroups but also by defining molecular pathways that are associated with these subgroups and that are possible targets for future therapies.In Section I, Dr. John Shaughnessy describes recent data obtained with GEP of CD138-purified plasma cells from patients with MM. His group has already shown that overexpression of the Wnt signaling inhibitor DKK1 by MM plasma cells blocks osteoblast differentiation and contributes to the development of osteolytic bone lesions. Recent data allow identification of four subgroups of MM in which GEP is highly correlated not only with different clinical characteristics and outcome but also with different cytogenetic abnormalities. In addition, abnormal expression of only three genes (RAN, ZHX-2, CHC1L) is associated with rapid relapses. In the context of intensive therapy with tandem autotransplantations, this model appears to be more powerful than current prognostic models based on standard biologic variables and cytogenetics. Understanding why the dysregulation of these three genes is associated with a more aggressive behavior of the disease will help to define new therapeutic strategies.In transplants yielding complete remission (CR) rates in excess of 60%, survival ranges from a few months to greater than 15 years. The extended time (almost 2 years) for those patients to achieve CR, and the even longer time to achieve magnetic resonance imaging (MRI)-CR, strongly suggests enormous tumor cell population heterogeneity in terms of drug responsiveness/resistance. Traditional prognostic factors, such as β2-microglobulin (β2M), albumin, and C-reactive protein (CRP), account for only 15%-20% of outcome heterogeneity. Abnormal metaphase karyotypes, present in one-third of newly diagnosed patients and reflecting stroma independence, have been consistently associated with a rapidly fatal outcome, and fewer than 10% of patients with these abnormalities survive > 5 years.Recent advances in molecular cytogenetics have identified primary translocations involving the immunoglobulin heavy chain locus at 14q32 in 40% of patients.5 According to a consensus report of a recent Paris workshop on myeloma genetics, hyperdiploid and t(11;14)(q13,q32)-positive myeloma are associated with a good prognosis, whereas non-hyperdiploidy, often associated with translocations other than t(11;14) and chromosome 13 deletion, imparts a strikingly dismal prognosis. 6Gene Expression Profiling of Myeloma Gene ...

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“…Alpha-interferon (IFN-a) has been successfully em ployed in the treatment of several hematologic malignan cies such as hairy cell leukemia (HCL) [1,2], chronic myeloid leukemia (CML) [3], non-Hodgkin's lymphoma (NHL) [4], essential thrombocythemia (ET) [5] and multi ple myeloma (MM) [6,7], while other indications are under investigation [8]. IFN-a therapy can cause long term side effects such as autoimmune thyroid dysfunc tions, development of other autoimmune diseases and the isolated appearance of autoantibodies.…”

Section: Introductionmentioning

confidence: 99%

Autoimmune Thyroid Dysfunctions in Hematologic Malignancies Treated with Alpha-lnterferon

Cavanna

Bertè

Merli³

et al. 1995

Acta Haematol

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The widespread use of alpha-interferon (IFN-α) therapy in different diseases draws attention to its side effects, such as autoimmune-related diseases, especially thyroid autoimmune dysfunctions. Data about hepatitis and nonhematologic neoplasia are available, while data about hematologic malignancies are fragmentary. We studied the incidence of autoimmune-related disturbances and thyroid dysfunctions in 54 consecutive patients suffering from hematologic malignancies, treated with recombinant human IFN-α for a mean time of 15.9 ± 8.9 months. Our results minimize the incidence of autoimmune dysfunctions in hematologic malignancies as side effects of IFN-α therapy. We registered the appearance of autoantibodies in only 3 females (5% of total): 2 patients (1 affected with essential thrombocythemia and one with multiple myeloma) presented antithyroglobulin antibodies with no clinical symptoms; 1 patient, affected with essential thrombocythemia, developed antinuclear antibodies with arthralgia and myalgia. ARA criteria for systemic lupus erythematosus were not fulfilled but the therapy had to be interrupted. No patient developed thyroid dysfunction. In patients with hematologic malignancies, the dosage and the duration of IFN-α treatment do not seem to influence the appearance of autoantibodies, while female sex appears to be a risk factor.

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Interferon plus Glucocorticoids as Intensified Maintenance Therapy Prolongs Tumor Control in Relapsed Myeloma

Cited by 14 publications

References 18 publications

Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients

Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients

Multiple Myeloma

Autoimmune Thyroid Dysfunctions in Hematologic Malignancies Treated with Alpha-lnterferon

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