Multiple myeloma mm is an incurable malignancy of terminally differentiated. Thalidomide in the management of multiple myeloma sciencedirect. Thalidomide is an oral immunomodulatory drug that is widely used throughout the myeloma disease course in the frontline, consolidationmaintenance, and relapse settings. In one controlled trial, the rate of venous thromboembolism. Neuropathy in multiple myeloma treated with thalidomide. Dec 04, 2010 it has been known for more than four decades that patients with multiple myeloma mm have an increased risk of venous thromboembolism vte. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Request pdf thalidomide and lenalidomide in multiple myeloma multiple myeloma is a treatable but not necessarily a curable plasmacell cancer. Every thalidomide prescription must be accompanied by a complete prescription authorisation form. There are currently between 10,000 and 15,000 people living with multiple myeloma in the uk. A followup of the original phase ii trial, expanded to 169. March 9 issue1 report an increased response rate of multiple myeloma to thalidomide plus highdose chemotherapy and transplantation. Thalidomide in refractory and relapsing multiple myeloma.
Thalidomide and hematopoieticcell transplantation for multiple myeloma somashekar krishna m arked and rapid onset of response has been widely recognized as critically important for longterm prognosis and cure in leukemias ie, chronic myeloid leukemia and acute promyelocytic leukemia that lend themselves to minimal residual disease mrd. It is a neoplastic disease of unknown etiology, characterized. Efficacy of low dose thalidomide t in multiple myeloma abstract. Very recently, the search for new active drugs prompted the use of thalidomide for treatment of advanced and refractory multiple myeloma, which gave an overall response rate of 32 to 37% in these patients 1, 2. Introductionmultiple myeloma is a plasma cell proliferative disorder that accounts for 10% of all malignant hematologic neoplasms. Thalidomide is also used to treat and prevent moderate to severe skin lesions caused by leprosy. Thrombosis in multiple myeloma hematology, ash education. Maintenance therapy with immunomodulatory drugs in multiple myeloma. Thalidomide thal has antiangiogenic and immunomodulatory activity. Results of a multicenter randomized clinical trial. Thalomid is an oral immunomodulatory drug, an agent that can modify or regulate the immune system. Efficacy of melphalan and prednisone plus thalidomide in.
More recently, thalidomide has been shown to prevent neoangiogenesis in human malignancies and to exert immunomodulatory and antiinflammatory properties, although the exact mechanism of action is unclear. Bortezomibthalidomidedexamethasone is superior to thalidomidedexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Thalidomide and hematopoieticcell transplantation in multiple myeloma. You will find out more about body changes and other things that can signal a problem that may need medical care. Much is known about how thalidomide works in the treatment of different diseases and how its side effects can be managed.
Apr 18, 2008 thalidomide is fdaapproved for use with dexamethasone in patients with newly diagnosed multiple myeloma. Multiple myeloma mm is the prototype of a spectrum of diseases known as plasma cell dyscrasias. Therapeutic application of thalidomide in multiple myeloma. This randomized, placebocontrolled, phase iii trial investigated the ef.
What is the role of thalidomide in the treatment of. Understanding thalidomide internl myeloma foundation. Myeloma group this is a controlled document and therefore must not be changed mm. Jul 26, 2001 we conducted a clinical trial of thalidomide as initial therapy for asymptomatic smoldering smm or indolent multiple myeloma imm. Bone marrow angiogenesis is increased in multiple myeloma mm patients, prompting the rationale for using antiangiogenic drugs in the treatment of these. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma. Thalidomide in the management of multiple myeloma taylor. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. However, a high incidence of side effects at the dosage initially recommended 400 mgday justified further studies with lower doses of thalidomide given alone or in combination with dexamethasone or.
Subscribe to our free newsletters to receive latest health news and alerts to your email inbox. Furthermore, cxcr4 expression on mm cells has been shown to be inversely correlated with disease activity multiple myeloma mm is a bcell neoplasm characterized by 2. The addition of thalidomide to this combination demonstrated a survival bene. Pdf thalidomide and hematopoieticcell transplantation. Pdf first thalidomide clinical trial in multiple myeloma. Treatment with thalidomide and dexamethasone was given to 26 patients with active, previously untreated multiple myeloma mm. Multiple myeloma is a rare type of cancer that affects bone marrow and alters your bloods plasma cells. Data from the 34patient trial were published in the international.
What is the role of thalidomide in the treatment of multiple. Hussein the design of innovative, more effective, less toxic therapy for multiple myeloma mm is emerging in parallel to a better understanding of the underlying pathophysiology of this common hematologic malignancy. Pdf adverse effects of thalidomide administration, in. Thalidomide is effective as a firstline therapy for the treatment of multiple myeloma mm, but its use is limited by peripheral neurotoxicity. Plasmacytomas are tumors, which typically form in the bone. 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. Thalidomide treatment in multiple myeloma sciencedirect.
Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3. Thalidomide, a derivate of glutamic acid, is increasingly used in patients with multiple myeloma mm singhal et al, 1999. Feb 08, 2019 a maintenance treatment with thalidomide at 100 mg a day was safe and seen to delay disease progression by more than three years in multiple myeloma patients with stable disease in a phase 2 study in japan, researchers report. Recent advances in the clinical application of these agents and in our understanding of their. Thalidomide is already authorised in other countries for multiple myeloma, including australia and the usa. Jul 01, 2006 thalidomide in newly diagnosed multiple myeloma a phase ii study by rajkumar et al demonstrated a response rate of 64% in 50 patients with newly diagnosed mm who were treated with thalidomide 200 mg per day and dexamethasone 40 mg on days 14, 912, and 1720 odd cycles, and 40 mg per day on days 14 even cycles repeated monthly in pulse. Mar 09, 2006 we assessed whether the addition of thalidomide, which has activity against advanced and refractory myeloma, would further improve survival.
According to the european medicines agency ema, thalidomide is approved in combination with melphalan and prednisone vmp in patients with newly diagnosed myeloma that are not candidates for autologous stem cell transplantation. Following the initial results, which demonstrated dramatic response rates in heavily pretreated patients, a number of phase ii studies have confirmed the efficacy of this agent in relapsed patients. It directly kills or suppresses the growth and survival of myeloma cells. It has both antiinflammatory and anticancer activities. Based on the promising results achieved in these patients, the drug was subsequently used in earlier. Thalidomide was first used to treat multiple myeloma in 1997. Review open access thalidomide and its analogues in. Single autologous stemcell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma. Thalidomide can now also be used as maintenance therapy after a stem cell transplant. The objectives of this study were to evaluate the response rates, overall survival, eventfree survival, and toxicity of thalidomide and dexamethasone administered until best response in recently diagnosed patients with multiple myeloma. Thalidomide was introduced in the treatment of multiple myeloma in the late 1990s. Bortezomib and thalidomide as first treatments for.
Immunomodulatory analogues of thalidomide in the treatment of. It explains guidance advice from nice the national institute for. The therapeutic efficacy of thalidomide n a derivative of glutamic acid n has been studied in numerous trials on refractoryrelapsed multiple myeloma mm. Whether you or someone you love has cancer, knowing what to expect can help you cope. Thalidomide celgene in combination with melphalan and prednisone is indicated as first line treatment of patients with untreated multiple myeloma, aged. Chemotherapy protocol multiple myeloma mptmelphalan po. Renal failure is a frequent complication of mm that is present in 50% of newly diagnosed patients kyle et al, 2003. Bortezomib and thalidomide as first treatments for multiple myeloma this leaflet is about when bortezomib and thalidomide should be used to treat people with multiple myeloma in the nhs in england and wales. First or subsequentline chemotherapy for multiple myeloma. The american society of clinical oncology notes that its relatively uncommon in the united states, affecting about one in every 2 people. Single nucleotide polymor multiple myeloma, an incurable bone marrow cancer, phisms snps in the vegf gene may contribute to this varia tion. It is used in patients who are older than 65 years or in younger patients if they cannot be treated with highdose chemotherapy or undergo stem cell transplant. Thalidomide was administered in an initial dosage of 200 mgd for 2 weeks and then increased as tolerated in 200mg increments at 2week intervals to a maximum daily dose of 800 mg.
What cancer patients, their families, and caregivers need to know about the coronavirus. Thalidomide and dexamethasone combination for refractory multiple. Consider either temporary treatment discontinuation or continuing treatment at a lower dose. Thalidomide is available only in a 28day supply from a certified pharmacy under a special program. Recently, thalidomide thal has been identified as a possible clonal expansion of plasma cells in the hematopoietic bone marrow potent inhibitor of cxcr4 5. European medicines agency recommends the approval of. List item european medicines agency recommends the approval of thalidomide for the treatment of rare bonemarrow cancer pdf 35. Antitumor activity of thalidomide in refractory multiple myeloma. Thalidomide in elderly patients with multiple myeloma. Thalidomide and its analogues in the treatment of multiple.
It is difficult to diagnose multiple myeloma early. Thalidomide celgene is prescribed and dispensed according to the thalidomide celgene pregnancy prevention programme see section 4. Apr 06, 2021 a randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and highdose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. A metaanalysis found that using circulating micrornas had high sensitivity. Thalidomide and hematopoieticcell transplantation for. Although a single drug may be used to treat multiple myeloma, it is preferable to use at least 2 or 3 different kinds of drugs in combination because the cancer responds better. Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and antiinflammatory effects. Request pdf thalidomide in refractory and relapsing multiple myeloma patients with multiple myeloma mm refractory to chemotherapy can only benefit from supportive measures and have a very. The emergence of thalidomide as a treatment for myeloma using thalidomide to treat myeloma is an idea that emerged in the 1990s, but thalidomide itself has been studied for many decades.
The immunomodulatory drug imid thalidomide and its newer analogs demonstrate increased antitumor activity, and have had a positive impact on the natural history of multiple myeloma. Clinical research provided clear evidence that thal is one of the most active drugs for the treatment of multiple myeloma. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic m. Both agents are associated with a low rate of serum aminotransferase elevations during therapy and both have been implicated in causing rare instances of clinically apparent liver injury which can be severe. Thalidomide celgene increased the time patients lived in one main study involving 447 patients with multiple myeloma. Thalidomide has recently been shown to have significant activity in refractory multiple myeloma mm. Dramatic response of diffuse osteosclerosis secondary. Skin prick and patch test results with thalidomide were negative, while the oral provocation test results were positive. Thalidomide and its analogue lenalidomide are immunomodulatory and antineoplastic agents that are used in the therapy of multiple myeloma. Myeloma also called multiple myeloma is a cancer that forms in white blood cells. Thalidomide and lenalidomide in multiple myeloma request pdf. Sep 11, 2012 multiple myeloma is an incurable malignant disorder of mature bcells that predominantly affects the elderly.
Mar 26, 2020 thalidomide is used together with dexamethasone to treat multiple myeloma bone marrow cancer. Multiple myeloma response to thalidomide as maintenance. Multiple myeloma is a rare cancer that affects bone marrow. Whether you or someone you love has cancer, knowing what to expect can. It was officially approved for use in treating myeloma in combination with the steroid dexamethasone in 2006. This publication is part of our treatment guide series, a collection of publications covering different drugs used in the treatment of myeloma. The signs and symptoms of myeloma vary with each person and stag. Multiple myeloma is a type of cancer that occurs when plasma cells become cancerous and produce plasmacytoma. Immunomodulatory analogues of thalidomide in the treatment of multiple myeloma revathi suppiah, j. The aim of this trial was to determine the maximum tolerated dose of panobinostat when given with subcutaneous bortezomib, plus thalidomide and dexamethasone in patients with relapsed, or relapsed and refractory, multiple myeloma, and determine the. Thalidomide metabolites in mice and patients with multiple. Data regarding thalidomide pharmacokinetics and tolerance in patients with renal failure are lacking. Immunomodulatory drugs induce immune responses, enhance the activity of immune cells, and inhibit inflammation by altering the levels of various growth factor. Lenalidomide or pomalidomide or thalidomide and dexamethasone.
Pdf thalidomide as initial therapy for earlystage myeloma. The study included patients over 65 years of age, as well as younger patients who could not be treated with highdose chemotherapy. The patient began receiving melphalan plus prednisolone mp regimen. The role of thalidomide in multiple myeloma sciencedirect. Review of thalidomide in the treatment of newly diagnosed multiple. Between october 1998 and february 2004, 668 patients with newly diagnosed multiple myeloma received two cycles of intensive melphalanbased chemotherapy, each supported by autologous hematopoietic. Thalidomide and dexamethasone induction therapy until.
Thalidomide treatment in multiple myeloma request pdf. Thalidomide in patients with multiple myeloma and renal. Thalidomide celgene previously thalidomide pharmion. Subscribe to hematology news a metaanalysis found that using circulating micrornas had high sensitivity and specificity in the early diagnosis of multiple myeloma. Pdf antitumor activity of thalidomide in refractory. A followup of the original phase ii trial, expanded to 169 patients, shows 2year survival of. Thalidomide and stemcell transplantation for multiple myeloma n engl j med 354. Multiple myeloma occurs when patients have more than one plasmacytoma. Urine or plasma samples from patients during thalidomide therapy 100400 mg daily, or from mice treated i.
Thalidomide aloneor with dexamethasone for multiple myeloma abstract. It typically affects the bones as the cancerous cells accumulate in a persons bone marrow. Fortyfour patients with refractory myeloma were treated with thalidomide, 200 mg p. The discovery that multiple myeloma is associated with new vessel formation and is correlated with survival and proliferation led initially to the use of thalidomide.
Thalidomide and dexamethasone induction therapy until best. This risk increases significantly when thalomid is used in combination with standard chemotherapeutic agents including dexamethasone. Using these drugs together to treat multiple myeloma. A publication of the international myeloma foundation multiple myeloma cancer of the bone marrow 12650 riverside drive, suite 206 north hollywood, ca 91607 usa telephone. Thalidomide for previously untreated indolent or smoldering. The study compared the effect of melphalan and prednisone, with or without thalidomide celgene. There are several theories on how thalidomide works, some or all of which may occur. In the uk, the estimated lifetime risk of developing multiple myeloma is 1 in 148 for men and 1 in 186 for women. This treatment guide contains information about thalidomide, a drug used in the treatment of myeloma.
Desensitization to thalidomide in a patient with multiple myeloma. Scientists still do not know exactly what causes most cases of multiple myeloma. Thalidomide and thrombosis in multiple myeloma barbui. Clinical and electrophysiologic examinations were performed in 31 patients with newly. Thalidomide therapy international myeloma foundation. Dec 01, 2002 the efficacy of thalidomide in multiple myeloma was first investigated in endstage myeloma patients in a compassionateuse protocol in the mid1990s. Bortezomib and thalidomide for the firstline treatment of. Thalidomide is a more targeted therapy than conventional chemotherapy. The use of thalomid in multiple myeloma results in an increased risk of venous thromboembolism, such as deep venous thrombosis and pulmonary embolism. Novel therapies for multiple myeloma are not affordable for all healthcare systems. Kmm166 study ki sun jung,1 kihyun kim,2 hyo jung kim,3 sung hyun kim,4 jeongok lee,5 jin seok kim,6 jejung lee,7 hyeonseok eom,8 changki min. Thalidomide is an old drug, withdrawn from clinical use in the 1960s because of its severe teratogenicity.
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