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

Hoevenaren, Ingrid A.; Vulpen, Lize F D van; Levenga, Henriëtte; Minnema, Monique C.; Raymakers, Reinier

doi:10.1038/bmt.2010.56

Cited by 5 publications

(2 citation statements)

References 8 publications

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“…12 Several groups tried to enhance this effect by combining DLI with immune modulatory drugs, such as thalidomide, bortezomib, and lenalidomide. [35][36][37] This resulted in partial and complete remissions, but cure was only achieved in a minority of patients. Also, repeated DLI does not result in new long-term remissions, especially not in the extramedullary compartment.…”

Section: Discussionmentioning

confidence: 99%

Donor T-cell responses and disease progression patterns of multiple myeloma

Eefting

Wreede

Borne

et al. 2017

Bone Marrow Transplant

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Donor T-cells transferred after allogeneic stem cell transplantation (alloSCT) can result in long-term disease control in myeloma by the graft-versus-myeloma (GvM) effect. However, T-cell therapy may show differential effectiveness against bone marrow (BM) infiltration and focal myeloma lesions resulting in different control and progression patterns. Outcomes of 43 myeloma patients who underwent T-cell-depleted alloSCT with scheduled donor lymphocyte infusion (DLI) were analyzed with respect to diffuse BM infiltration and focal progression. For comparison, 12 patients for whom a donor search was started but no alloSCT was performed, were analyzed. After DLI, complete disappearance of myeloma cells in BM occurred in 86% of evaluable patients. The probabilities of BM progression-free survival (PFS) at 2 years after start of donor search, alloSCT and DLI, were 17% (95% confidence interval 0-38%), 51% (36-66%), and 62% (44-80%) respectively. In contrast, the probabilities of focal PFS at 2 years after start of donor search, alloSCT and DLI, were 17% (0-38%), 30% (17-44%) and 28% (11-44%), respectively. Donor-derived T-cell responses effectively reduce BM infiltration, but not focal progression in myeloma, illustrating potent immunological responses in BM with only limited effect of T-cells on focal lesions.

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Section: Discussionmentioning

confidence: 99%

Donor T-cell responses and disease progression patterns of multiple myeloma

Eefting

Wreede

Borne

et al. 2017

Bone Marrow Transplant

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“…The 3-year PFS and OS rates were 33% and 78%, respectively. In a retrospective analysis conducted by Hoevenaren and colleagues [19], 30 MM patients received a median of 4.4 bortezomib courses for persistent or relapsed disease after alloSCT, and 21 also received escalating DLIs after the first 2 or 3 bortezomib courses. The RR to the entire treatment was 60%, with a median PFS rate of 12.7 months.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib Plus Dexamethasone Followed by Escalating Donor Lymphocyte Infusions for Patients with Multiple Myeloma Relapsing or Progressing after Allogeneic Stem Cell Transplantation

Montefusco

Spina

Offidani

et al. 2013

Biology of Blood and Marrow Transplantation

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Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen-identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective.

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Harnessing Allogeneic Immunity for Anti-myeloma Response

Bellucci

Alyea

2012

Advances in Biology and Therapy of Multiple Myeloma

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

Cited by 5 publications

References 8 publications

Donor T-cell responses and disease progression patterns of multiple myeloma

Donor T-cell responses and disease progression patterns of multiple myeloma

Bortezomib Plus Dexamethasone Followed by Escalating Donor Lymphocyte Infusions for Patients with Multiple Myeloma Relapsing or Progressing after Allogeneic Stem Cell Transplantation

Harnessing Allogeneic Immunity for Anti-myeloma Response

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