Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma

Giralt, Sergío; Aleman, Ana; Anagnostopoulos, Athanasios; Weber, Donna M.; Khouri, Issa F.; Anderlini, Paolo; Molldrem, Jeffrey J.; Ueno, Naoto T.; Donato, Michèle; Körbling, Martin; Gajewski, James; Alexanian, Raymond; Champlin, Richard E.

doi:10.1038/sj.bmt.1703652

Cited by 134 publications

(84 citation statements)

References 49 publications

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“…Even if the true value of lenalidomide post allograft can only be determined by a prospective randomised study, the relative long PFS of 52% at 3 years is higher than the reported 3-year PFS in similar allogeneic studies without lenalidomide. 2,3,8,9 In the current trial, neither del 13q14 or the use of mismatch donors could be identified as risk factor for survival. As data about t(4;14) or 17p were not available in all patients, a detailed cytogenetic impact could not be investigated.…”

Section: Discussionmentioning

confidence: 99%

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Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

Kröger

Zabelina

Klyuchnikov

et al. 2012

Bone Marrow Transplant

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Relapse after dose-reduced allograft in advanced myeloma patients remains high. To reduce the risk of relapse, we investigated a myeloablative toxicity-reduced allograft (aSCT) consisting of i.v. BU and CY followed by lenalidomide maintenance therapy in 33 patients with multiple myeloma (MM) who relapsed following an autograft after a median of 12 months. The cumulative incidence of non-relapse mortality at 1 year was 6% (95% confidence interval (CI): 0-14). After a median interval of 168 days following aSCT, 24 patients started with a median dose of 5 mg (r, 5-15) lenalidomide without dexamethasone. During follow-up, 13 patients discontinued lenalidomide owing to progressive disease (n ¼ 6), GvHD (n ¼ 3), thrombocytopenia (n ¼ 2), or fatigue (n ¼ 2). Major toxicities of lenalidomide were GvHD II-III (28%), viral reactivation (16%), thrombocytopenia (III-IV1,16%), neutropenia (III/IV1, 8%), peripheral neuropathy (I/II1, 16%), or other infectious complication (8%). Cumulative incidence of relapse at 3 years was 42% (95% CI: 18-66). The 3-year estimated probability of PFS and OS was 52% (95% CI: 28-76) and 79% (95% CI: 63-95), respectively. Toxicityreduced myeloablative allograft followed by lenalidomide maintenance is feasible and effective in relapsed patients with MM, but the induction of GvHD should be considered.

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Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8] In comparison to standard myeloablative conditioning regimen, reduced-intensity conditioning regimen resulted in lower non-relapse mortality (NRM) but also in a higher risk of relapse. 9 Retrospective studies suggest that the intensity of the conditioning regimen correlates with the risk of relapse.…”

Section: Introductionmentioning

confidence: 99%

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

Kröger

Zabelina

Klyuchnikov

et al. 2012

Bone Marrow Transplant

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“…[22][23][24] Two German studies and a study from the MD Anderson center confirmed 2-year survivals of 26-50% for patients who had failed one or more autologous transplants. A study combining data from several centers, including approximately 120 patients, found that relapse from a prior autologous transplant was the most significant risk factor for transplant mortality (HR 2.80; P = 0.02), relapse (HR 4.14; P < 0.001), and death (HR 2.69; P = 0.005).…”

Section: Non-ablative Allogeneic Transplantsmentioning

confidence: 99%

“…[21] Several other studies of reduced-intensity allografts from family members or unrelated donors have confirmed that results are poor when patients have failed a prior autologous transplant or have chemotherapy-resistant disease. [22][23][24] Two German studies and a study from the MD Anderson center confirmed 2-year survivals of 26-50% for patients who had failed one or more autologous transplants. A study combining data from several centers, including approximately 120 patients, found that relapse from a prior autologous transplant was the most significant risk factor for transplant mortality (HR 2.80; P = 0.02), relapse (HR 4.14; P < 0.001), and death (HR 2.69; P = 0.005).…”

Section: Non-ablative Allogeneic Transplantsmentioning

confidence: 99%

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Bensinger

2007

Best Practice & Research Clinical Haematology

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Despite significant improvements in survival for multiple myeloma patients through autologous stem-cell transplantation (SCT) and the introduction of novel drugs, the disease remains incurable for all but a small fraction of patients. Only allogeneic SCT is potentially curative, due in part to a graft-versus-myeloma effect. High transplant-related mortality with allogeneic SCT is currently the major limitation to wider use of this potentially curative modality. Mortality can be reduced through the use of lower-intensity conditioning regimens which allow engraftment of allogeneic stem cells, but this comes at a cost of higher rates of disease progression and relapse. Promising studies to improve outcomes of allogeneic transplants include the use of more intensive nonmyeloablative conditioning regimens, tandem transplants, peripheral blood cells, graft engineering to improve the graft-versus-myeloma activity while reducing graft-versus-host disease (GVHD), post-transplant maintenance, and targeted conditioning therapies such as bone-seeking radioisotopes. Keywords multiple myeloma; allogeneic stem-cell transplantationThe treatment of multiple myeloma has dramatically improved in the last 10 years. Highdose therapy followed by autologous stem-cell support has emerged as a promising means for increasing remission rates and improving survival. As such, autologous stem-cell transplantation has become the standard of care for many patients with multiple myeloma. In addition, insights into the biology and genetics of myeloma cells have resulted in the rapid introduction of new drugs with unique mechanisms of action. These drugs -which include thalidomide, lenalidomide and bortezomib -have shown significant activity in multiple myeloma, and when these new agents are combined with more traditional drugs, the response and complete remission rates are as high as responses achieved with autologous stem-cell transplantation. [1,2] Despite these advances, long-term survival after treatment with stem-cell transplantation or the newly developed drugs is rare, and disease recurs in virtually all patients.Stem-cell transplantation from allogeneic donors may be curative for 10-20% of patients with chemotherapy-resistant, refractory hematologic malignancies, and for up to 80% of . E-mail address: wbensing@fhcrc.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. patients who are transplanted in remission. Much of the high response and curative potential of allografts is attributed to a 'graft-versus-tumor' effect. In patients with multiple myeloma this effect has been well documented...

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“…21,22 Thus in the 2000s, more patients received allotransplant using RIC regimens, usually with melphalan 100-140 mg/m 2 with or without other agents. 23 A CIBMTR (Center for International Blood and Marrow Transplant Research) analysis demonstrated a major practice switch to nonmyeloablative and RIC-based allo-SCT with concomitant reduction in the number of myeloablative allografts performed in the years 2001-2005 compared with the two preceding 5-year intervals.…”

Section: Non-myeloablative/reduced-intensity Conditioningmentioning

confidence: 99%

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

Dhakal

Vesole

Hari

2016

Bone Marrow Transplant

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Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma

Abstract: Summary:The purpose of the study was to determine the feasibility and efficacy of a reduced intensity conditioning regimen of fludarabine and melphalan for allogeneic transplantation in patients with multiple myeloma.

Cited by 134 publications

References 49 publications

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

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