Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma

Donk, Niels W.C.J. van de; Kröger, Nicolaus; Hegenbart, Ute; Corradini, Paolo; Miguel, Jesús F. San; Goldschmidt, Hartmut; Pérez-Simón, José A.; Zijlmans, Mark; Raymakers, Reinier; Montefusco, Vittorio; Ayuk, Francis; Oers, Marinus H. J. van; Nagler, Arnon; Verdonck, Leo F.; Lokhorst, Henk M.

doi:10.1182/blood-2005-11-4449

Cited by 73 publications

(47 citation statements)

References 8 publications

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“…[1][2][3] To upgrade remission or to prevent or to treat relapse, several therapies such as donor lymphocyte infusions, 4,5 or novel agents such as bortezomib or thalidomide [6][7][8][9] have been investigated after allo-SCT. As the so-called 'IMIDs' (immunomodulatory drugs), thalidomide and lenalidomide, induce enhanced T-cell activation and NK-cell activation, it could be a useful track to enhance graft-vs-myeloma effect after allo-SCT.…”

Section: Introductionmentioning

confidence: 99%

Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44+) and T (HLA-DR+) cells

Lioznov

El-Cheikh

Hoffmann

et al. 2009

Bone Marrow Transplant

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We investigated efficacy and toxicity of lenalidomide in 24 heavily pretreated myeloma patients with a median age of 59 years (range: 37-70) and relapse after allo-SCT. Lenalidomide was given at a dose of 15 mg (n ¼ 4), or 25 mg (n ¼ 20), orally once daily on day 1 to day 1 every 28 days, with (n ¼ 20) or without (n ¼ 4) DHAP. The median number of lenalidomide cycles was five (range: 2-17). Major side effects were leukopenia (grade 4: 4%, grade 3: 21% and grade 2: 17%) and thrombocytopenia (grade 3: 17% and grade 2: 29%); infectious complications were observed in 50%. Non-hematological toxicity consisted of muscle cramps (n ¼ 9), fatigue (n ¼ 5) and constipation (n ¼ 2). Mild grade I-II GVHD was seen in three patients. Response was achieved in 66%: CR in 8%, VGPR in 8%, PR in 50% and SD in 13%. The median time to progression was 9.7 months (95% confidence interval (CI): 7.5-11.9), and median OS was 19.9 months (95% CI: 17.3-22.5). Immunomonitoring after lenalidomide showed significant increase of activated NK (NKp44 þ ) and T (HLA-DR þ ) cells, as well as regulatory T cells (CD4 þ , CD25 þ , CD127 lo ), supporting an immunomodulating anti-myeloma effect of lenalidomide.

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Section: Introductionmentioning

confidence: 99%

Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44+) and T (HLA-DR+) cells

Lioznov

El-Cheikh

Hoffmann

et al. 2009

Bone Marrow Transplant

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“…Van de Donk et al 5 evaluated DLIs for relapsed (n ¼ 48) or persistent (n ¼ 15) MM following non-myeloablative allo-SCT. A response in 38% of the patients with a 19% CR was seen.…”

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confidence: 99%

“…[3][4][5] The dissociation of GVHD and GVT is of vital importance in improving the efficacy of alloSCT and DLI. In this analysis we retrospectively collected data on the efficacy of bortezomib re-induction therapy in patients with relapsed or persistent MM after allo-SCT and the effect of the combination with DLI.…”

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confidence: 99%

“…In patients with more than a partial response this was followed by DLI to boost graft-versus-myeloma reactivity and to further improve the remission status, as DLI is considered a standard treatment policy in relapsed or persistent myeloma after allo-SCT. 5 The patient population included 23 male and 7 female patients with a median age of 59 years (range 38-75 years). All patients were treated according to standard first-line protocols, followed by allo-SCT.…”

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confidence: 99%

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Bortezomib and donor lymphocyte infusion in multiple myeloma relapsed after allo-SCT does not result in durable remissions

Hoevenaren

Vulpen²,

Levenga

et al. 2010

Bone Marrow Transplant

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“…The combina-tion of bortezomib and thalidomide has been used in a small cohort of patients with relapsed multiple myeloma post-AlloSCT. 62 The authors evaluated DLIs given for relapsed (n ¼ 48) or persistent (n ¼ 15) multiple myeloma following RIC AlloSCT. Twenty-four (38.1%) of 63 patients responded to DLI.…”

Section: Is Allosct the Penultimate Intervention? Post-allosct Therapymentioning

confidence: 99%

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

Cook

Bird

Marks

2008

Bone Marrow Transplant

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AlloSCT is a potentially curative procedure for haematological malignancies and marrow failure syndromes. However, unlike leukaemia and lymphoproliferative disorders, AlloSCT has yet to find its place in the clinical management of patients with multiple myeloma. AlloSCT in multiple myeloma is associated with a high procedurerelated mortality (TRM up to 35%) when full-intensity conditioning is used and only up to 36% of cases show long-term disease-free survival. The introduction of reduced intensity conditioning AlloSCT, more recently following an autologous SCT, has reduced the TRM to o20%, but there is an associated increased relapse risk. The use of donor lymphocyte infusions and novel biological agents (thalidomide, bortezomib), alone or together, can be effective in relapsed and even persistent disease post-AlloSCT. Thus, in pursuit of the putative graft-versus-myeloma effect, we need to consider the whole patient management pathway both preceding (depth of response to novel agents) and post-AlloSCT, to minimize the toxicity while harnessing the adoptive immunotherapy effect. This review sets out what we have learned to date from the clinical research studies in this area, examines concepts for improving the outcomes of AlloSCT and proposes a potential direction of clinical investigation to maximize the effect of AlloSCT in multiple myeloma.

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Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma

Cited by 73 publications

References 8 publications

Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44+) and T (HLA-DR+) cells

Lenalidomide as salvage therapy after allo-SCT for multiple myeloma is effective and leads to an increase of activated NK (NKp44+) and T (HLA-DR+) cells

Bortezomib and donor lymphocyte infusion in multiple myeloma relapsed after allo-SCT does not result in durable remissions

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

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