LA CONSULTA SEMANAL

CONSULTA

1: Mayo Clin Proc 2003 Jan;78(1):34-9 [Texto completo]

Response rate, durability of response, and survival after thalidomide therapy for relapsed multiple myeloma.

Kumar S, Gertz MA, Dispenzieri A, Lacy MQ, Geyer SM, Iturria NL, Fonseca R, Hayman SR, Lust JA, Kyle RA, Greipp PR, Witzig TE, Rajkumar SV.

Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA.

OBJECTIVE: To assess response rate, duration of response, progression-free survival, and toxicity of thalidomide in patients with relapsed multiple myeloma. PATIENTS AND METHODS: Thirty-two patients with relapsed multiple myeloma were entered into the study between April 29, 1999, and June 20, 2000. They were given oral thalidomide at a dosage of 200 mg/d for 2 weeks, which was then increased as tolerated to a maximum of 800 mg/d. The primary end point of the study was response rate. RESULTS: The median age of the patients was 67 years (range, 36-78 years). Prior chemotherapy had failed in all patients, and stem cell transplantation had failed in 5 patients (16%). There were 10 confirmed responses, yielding a response rate of 31%. In addition, there was 1 unconfirmed partial response and 7 minimal responses with no complete responses. The median duration of response was 11.9 months (range, 3.7-203 months). Overall, 20 patients have died, and 26 patients have experienced disease progression. The median follow-up of surviving patients was 28.5 months (range, 193-34.0 months), with a median progression-free survival of 8.6 months (95% confidence interval [CI], 4.7-16 months). The median progression-free survival among the responding patients was 15.7 months (95% CI, 8.6-25.6 months). The median overall survival for the entire group was 22 months (95% CI, 10.6-35.9 months). The most common treatment-related nonhematologic toxic effects (grade >3) were neuropathy (16%), sedation (13%), febrile neutropenia (6%), and constipation (6%). CONCLUSIONS: Thalidomide is useful in the treatment of patients with relapsed multiple myeloma and produced durable response in approximately one third of patients, with median response duration of nearly 1 year.

2: Mayo Clin Proc 2003 Jan;78(1):21-33 [Texto completo]

Review of 1027 patients with newly diagnosed multiple myeloma.

Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, Plevak ME, Therneau TM, Greipp PR.

Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA. kyle.robert@mayo.edu

OBJECTIVE: To determine the clinical and laboratory features of newly diagnosed multiple myeloma. PATIENTS AND METHODS: Records of all patients in whom multiple myeloma was initially diagnosed at the Mayo Clinic in Rochester, Minn, from January 1, 1985, to December 31, 1998, were reviewed. RESULTS: Of the 1027 study patients, 2% were younger than 40 years, and 38% were 70 years or older. The median age was 66 years. Anemia was present initially in 73% of patients, hypercalcemia (calcium level > or = 11 mg/dL) in 13%, and a serum creatinine level of 2 mg/dL or more in 19%. The beta2-microglobulin level was increased in 75%. Serum protein electrophoresis revealed a localized band in 82% of patients, and immunoelectrophoresis or immunofixation showed a monoclonal protein in 93%. A monoclonal light chain was found in the urine in 78%. Nonsecretory myeloma was recognized in 3% of patients, whereas light-chain myeloma was present in 20%. Conventional radiographs showed an abnormality in 79%. The plasma cell labeling index was 1% or more in 34% of patients. Multivariate analysis revealed that age, plasma cell labeling index, low platelet count, serum albumin value, and the log of the creatinine value were the most important prognostic factors. CONCLUSION: The median duration of survival was 33 months and did not improve from 1985 through 1998.

3: Mayo Clin Proc 2003 Jan;78(1):15-7 [Texto completo]

Multiple myeloma: how far have we come?

Anderson KC.

Publication Types: Comment Editorial Review

4: Semin Oncol 2002 Dec;29(6 Suppl 17):26-33

High-dose therapy and immunomodulatory drugs in multiple myeloma.

Barlogie B, Shaughnessy J, Zangari M, Tricot G.

Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

The principle of alkylating agent dose intensity, especially with melphalan-based tandem autotransplants, has been effective in increasing the rate of complete remission beyond 40% and effecting 10-year survivorship in about 40% of the three fourths of patients presenting without cytogenetic abnormalities (Total Therapy I). Further dose escalation and post-transplant consolidation therapy, as practiced with Total Therapy II, seems to further improve results in these patients, but not in those with chromosome 13 abnormalities or lactate dehydrogenase elevation. Phase III trials for post-transplant relapse indicate higher complete remission and near-complete remission rates among patients randomized to thalidomide added to dexamethasone versus dexamethasone alone. In a phase I/II study, thalidomide derivative CC-5013, with less sedative and neurotoxic effects, promoted responses in eight of 15 patients with post-transplant relapse, refractory to other salvage therapies, at dose levels of > or = 25 mg daily. Based on a profound graft-vs-myeloma effect with allografts, mini-allotransplants were evaluated in 31 high-risk patients with cytogenetic abnormalities and prior autotransplants; all nine with responsive disease and only one prior autotransplant remain disease-free and alive. Such mini-allotransplants are now offered as consolidation after one standard autotransplant to patients with cytogenetic abnormalities. The systematic application of gene expression profiling attempts to classify multiple myeloma (MM) patients according to molecular features and to dissect the genetic basis for drug sensitivity or resistance. Given the availability of an expanding treatment armamentarium (eg, thalidomide, CC-5013, the proteasome inhibitor PS-341, farnesyltransferase inhibitors, IL-6 receptor antibody, endothelial receptor inhibitor), gene expression profiling is anticipated to help in the selection of agents with the greatest probability of activity toward individualized treatment. Careful scrutiny of gene expression will also help in the identification of unrecognized targets for therapeutic intervention. Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types: Review

5: Semin Oncol 2002 Dec;29(6 Suppl 17):21-5

Drug resistance and drug development in multiple myeloma.

Dalton WS.

College of Medicine, University of Arizona Health Science Center, PO Box 245017, Tucson, AZ 85724, USA.

Circumvention of drug resistance in multiple myeloma is a major obstacle to improving clinical outcomes for myeloma patients. Identification of several mechanisms of acquired drug resistance has led to the development of chemosensitizing agents that counter specific drug resistance mechanisms. Initial successes in therapy using chemosensitizers often culminate in relapse because of the multifactorial nature of acquired multidrug resistance. Therefore, it may be important to design therapeutic strategies that focus on mechanisms that allow for cell survival following initial treatments, before the acquisition of multidrug resistance. It has been proposed that extracellular effectors such as cytokines, matrix components, and adjacent cells may provide a sanctuary for cancer cells by preventing stress-induced cell death. This review focuses on research implicating the cancer cell environment as a particularly important determinant in the emergence of drug resistance. Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types: Review

6: Semin Oncol 2002 Dec;29(6 Suppl 17):11-6

Advances in the biology and treatment of myeloma bone disease.

Berenson JR.

Multiple Myeloma and Bone Metastasis Program, Cedars-Sinai Medical Center, University of California Las Angeles School of Medicine, 8700 Beverly Boulevard, Bev. Mod. 1, Room 100, Los Angeles, CA 90402, USA.

The major clinical manifestations of multiple myeloma are related to the loss of bone. This bone loss often leads to pathologic fractures, spinal cord compression, hypercalcemia, and bone pain. This article reviews the cytokine network involved in myeloma bone disease; describes the signaling cascade involved in osteoclastogenesis and mechanisms of action of novel therapeutic options for myeloma bone disease such as osteoprotegerin, RANK human immunoglobulin fusion protein, the proteasome inhibitor PS-341, and bisphosphonates; and summarizes the latest clinical trial results using oral and intravenous bisphosphonates for bone disease in multiple myeloma. Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types: Review

7: Semin Oncol 2002 Dec;29(6 Suppl 17):5-10

Myeloma and the newly diagnosed patient: a focus on treatment and management.

Rajkumar SV, Kyle RA, Gertz MA. Mayo Medical School, 200 First Street SW, Rochester, MN 55905, USA.

An evidence-based approach to the management of newly diagnosed multiple myeloma, developed at the Mayo Clinic (Rochester, MN), is summarized in this article. The optimum pretransplant induction regimen for multiple myeloma is described, and outcomes for early and delayed transplantation, one versus two transplants, the role of thalidomide in smoldering multiple myeloma, and the role of maintenance therapy are discussed. The role of supportive care strategies for patients with bone disease, such as the use of bisphosphonates, is also discussed. Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types: Review

8: Br J Haematol 2003 Jan;120(1):10-7

Novel therapies for multiple myeloma.

Hayashi T, Hideshima T, Anderson KC.

Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Publication Types: Review

9: Clin Obstet Gynecol 2002 Sep;45(3):928-38

Multiple myeloma.

Podczaski E, Cain J.

Department of Obstetrics and Gynecology, The Pennsylvania State University School of Medicine, The Milton S Hershey Medical Center, Hershey 17033, USA. epodczaski@psu.edu

Publication Types: Review

10: Mayo Clin Proc 2002 Aug;77(8):813-22 [Texto completo]

Current therapy for multiple myeloma.

Rajkumar SV, Gertz MA, Kyle RA, Greipp PR;

Mayo Clinic Myeloma, Amyloid, and Dysproteinemia Group. Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA. rajks@mayo.edu

Multiple myeloma is an incurable plasma cell malignancy that accounts for 10% of all hematologic cancers. For decades the mainstay of therapy has been the use of melphalan and prednisone; with this regimen, the median survival is approximately 3 years. Recently, important advances were made that have substantially altered the manner in which patients with myeloma are treated. Newly diagnosed patients with good performance status are now treated with autologous stem cell transplantation, resulting in improved survival. Because of the increasing use of transplantation as initial therapy, several therapeutic issues have emerged: the role of tandem transplantation, early vs delayed transplantation, and the role of allogeneic transplantation. The pronounced activity of thalidomide in patients with refractory myeloma represents another important advance. This has prompted the study of several novel agents in the treatment of myeloma, at least 2 of which appear promising. Supportive care measures also have improved, including the use of bisphosphonates to prevent osteolytic lesions. The purpose of this review is to summarize recent advances and provide an evidence-based approach to the treatment of multiple myeloma.

Publication Types: Review

11: Curr Treat Options Oncol 2000 Apr;1(1):73-82

Multiple myeloma.

Raje N, Anderson KC.

Adult Oncology, Dana-Farber Cancer Institute Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Multiple myeloma (MM) is an incurable plasma cell dyscrasia that remains fatal. Despite efforts over the past 3 to 4 decades, the median survival of patients with MM does not exceed 3 to 4 years. Although patients receiving combination chemotherapy have higher response rates compared with those receiving oral melphalan and prednisolone, they have no survival advantage. High-dose chemotherapy followed by autologous stem cell transplantation has documented benefit over conventional treatment and is currently the accepted mode of treatment for symptomatic MM. Allogeneic transplantation is associated with high complete remission rates, but at the cost of high therapy-related mortality. Maintenance treatment with interferon-alpha shows benefit, albeit in a small fraction of MM patients. The use of bisphosphonates in patients with MM has clearly demonstrated benefit and reduced morbidity associated with bone disease. All of these measures have improved remission rates and survival, but all patients with MM ultimately relapse and succumb to their disease. Novel therapeutic strategies are therefore required to improve outcome of MM patients. The responses noted to thalidomide in MM are encouraging. Immune-based strategies, including both adoptive immunotherapy and vaccinations, are currently being investigated in the preclinical and clinical setting, with the goal of enhancing autologous and allogeneic anti-MM immunity for therapeutic applications.

Publication Types: Review

12: Ann Hematol 2001 Aug;80(8):445-51

Advances in the biology and therapeutic management of multiple myeloma.

Kaufmann H, Urbauer E, Ackermann J, Huber H, Drach J.

Department of Internal Medicine I, University of Vienna, Austria.

During the past decade, new developments have increased our understanding of the biological features of multiple myeloma (MM), and novel therapeutic approaches have improved the outcome and quality of life. The importance of both the malignant clone and the bone marrow environment for disease evolution and propagation has been recognized, and therapeutic approaches that target both components of the disease process appear to be most promising. Along this line, thalidomide has been observed to exert activity in chemotherapy-refractory MM and thus expands the therapeutic armamentarium against MM. Use of high-dose melphalan with autologous stem cell transplantation has resulted in an improved rate of complete remissions as well as prolonged event-free and overall survival. Novel treatment strategies exploiting anti-myeloma immunity (nonmyeloablative allogeneic transplantation, vaccination) are being investigated and carry the potential to further improve the outcome of patients with MM.

Publication Types: Review