Efficacy of thalidomide therapy for extramedullary relapse of myeloma following allogeneic transplantation

Abstract

Summary:Treatment options for patients with myeloma who relapse after allogeneic stem cell transplantation are limited. Thalidomide, an antineoplastic agent, has been shown to be effective in multiple myeloma through proposed mechanisms that may include angiogenesis inhibition. Herein we report successful thalidomide treatment of four patients who relapsed following allogeneic transplantation, three of whom had predominantly extramedullary relapse. Thalidomide was well tolerated in all patients; in two patients interferon-␣ was subsequently added to thalidomide as maintenance therapy without worsening graft-versus-host disease. We suggest that extramedullary myeloma is particularly sensitive to thalidomide, speculating that growth biology may in part be dependent on angiogenesis. Bone Marrow Transplantation (2001) 28, 1145-1150. Keywords: myeloma; thalidomide; transplantation; extramedullary; allogeneic; graft-versus-host disease Management options for multiple myeloma (MM) include autologous stem cell transplantation (autoSCT) and allogeneic bone marrow/stem cell transplantation (alloBMT). [1][2][3] Following alloBMT, a graft-versus-myeloma (GVM) effect is well recognized and may contribute to sustained molecular remission. 4-6 However, treatment options for relapse following alloBMT are often limited by concomitant graft-versus-host disease (GVHD), hematologic cytopenias or poor performance status.Thalidomide has antineoplastic properties, through proposed mechanisms that include angiogenesis inhibition, immunomodulation, apoptotic mechanisms, and modulation of T cell function. [7][8][9][10] In myeloma, angiogenesis as measured by microvessel density (MVD) has correlated with disease activity and outcome. [11][12][13] There is also recent evidence that thalidomide is active in vitro against MM cell lines resistant to standard chemotherapy. 14 Recently pub- lished studies have demonstrated activity of thalidomide in relapsed or refractory MM, 15-17 including patients who had had autoSCT. 18 To date there are no published data specifically examining the role of thalidomide for relapse after alloBMT.Trials investigating the role of interferon-␣ (IFN) in induction and maintenance phases of disease have yielded conflicting results. A recent meta-analysis demonstrated a survival advantage in this setting, suggesting that maintenance therapy may be of benefit. 19 We have concluded a clinical trial evaluating the efficacy of thalidomide, with IFN as maintenance treatment, in the management of relapsed or refractory MM. Four of the 75 patients accrued relapsed after HLA-identical sibling alloBMT. Herein we report successful thalidomide treatment in these four patients, three of whom had predominantly extramedullary (EM) relapse. Furthermore, we describe two of these patients who have proceeded to IFN maintenance therapy while on thalidomide. Issues related to EM relapse and the effects of the combination of thalidomide and IFN on disease control and GVHD are discussed. Study design of thalidomide trialPatients were pro...

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

“…47 However, other authors have highlighted responses in this case to thalidomide. 48,49 The present study shows that although patients with extramedullary myelomatous lesions may respond to ThaCyDex, this feature is associated with a poorer overall response and shorter survival, which indicates that the presence of this type of lesion is an adverse prognostic factor in patients treated with regimens containing thalidomide.…”

Extramedullary relapses after allogeneic non-myeloablative stem cell transplantation in multiple myeloma patients do not negatively affect treatment outcome

“…The use of these novel agents for the treatment of relapse after allogeneic SCT appears to be very successful. Biagi et al 8 have shown a good response in three patients treated with thalidomide 300-800 mg daily without the use of DLI. This was also shown by Van de Donk et al 18 for the treatment of non-EM relapses or progressive disease not responsive to DLI.…”

“…7,8 Therefore, we investigated the incidence and treatment of EM relapses in a large group of MM patients, all treated with an autologous SCT followed within 2-6 months by allogeneic NMA SCT.…”

Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission

“…5 Alternative treatment options for localised relapse may also be considered, since a recent report describes the successful use of thalidomide therapy in four patients with myeloma who relapsed 3-4 years post allograft with predominantly extramedullary disease. 9 It is also of interest to note that there was no evidence of molecular disease by IgH PCR, monitoring in any of the four patients presented with localised relapse in whom it was studied. Indeed, the value of PCR monitoring in the detection of early relapse postallograft for myeloma must be questioned in the light of these findings.…”

“…A review of the literature suggests that similar localised or extramedullary relapse has been observed by several other authors after allogeneic transplantation for myeloma and may, in fact, be a frequent finding. [4][5][6][7][8][9] Patients and methods A total of 25 patients who received allogeneic transplants from matched-sibling donors for multiple myeloma (n ¼ 23) or plasma cell leukaemia (n ¼ 2) in a single centre from 1991 to 2000 were studied. Patient characteristics are shown in Table 1.…”