High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after reduced intensity conditioning allogeneic stem cell transplantation for multiple myeloma

El-Cheikh, Jean; Michallet, Mauricette; Nagler, Arnon; Lavallade, Hugues de; Nicolini, Franck E.; Shimoni, Avichai; Faucher, Catherine; Sobh, Mohamad; Revesz, Daniela; Hardan, Izhar; Fürst, Sabine; Blaise, Didier; Mohty, Mohamad

doi:10.3324/haematol.12184

Cited by 60 publications

(39 citation statements)

References 19 publications

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“…12 These data also suggest a higher efficacy of lenalidomide in comparison to thalidomide (ORR 29%) 6 and at least a comparable efficacy to that of bortezomib (ORR 61-73%). [16][17][18] With a median follow up of 16.3 months, the median PFS was 18 months and the median OS was 30.5 months; results that appear superior to those reported with thalidomide (median OS of 12 months) 6 and bortezomib (median PFS of 6 months) 16,17 within comparable settings. In our cohort, the only significant factor influencing PFS and OS was abnormal cytogenetics.…”

Section: Discussionmentioning

confidence: 56%

Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the French Society of Bone Marrow and Cellular Therapy

et al. 2012

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Section: Discussionmentioning

confidence: 56%

Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the French Society of Bone Marrow and Cellular Therapy

et al. 2012

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“…37 They may still demonstrate remarkable responses to the novel agents alone or in combination with DLI. 38,39 In particular, thalidomide and lenalidomide may induce T-cell and natural-killer (NK) cell activity against the myeloma, whereas bortezomib may inhibit GVHD while maintaining the GVM effect. These responses explain the wide separation of PFS and OS curves seen in this and other studies, and why the plateau in survival curves is only seen 4 to 5 years after SCT.…”

Section: Discussionmentioning

confidence: 99%

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

Shimoni

Hardan

Ayuk

et al. 2010

Cancer

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BACKGROUND: Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced-intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long-term outcome of RIC in the recurrent/refractory setting. METHODS: A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine-melphalan based conditioning and stem cell grafts from a related (n ¼ 27) or unrelated donor (n ¼ 23). RESULTS: The median age was 53 years. Forty-seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow-up of 6.4 years (range, 5-7.9 years), the overall and progression-free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7-year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome. CONCLUSIONS: Allogeneic SCT can result in long-term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010;116;3621-30.

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“…In a retrospective study of 37 patients with multiple myeloma treated with reduced intensity allogeneic HSCT, 11 patients showed responses with 3 responses in patients with severe cGVHD. Eight patients with limited disease did not require any additional immunosuppressive therapy [154]. Other trials have also shown activity of bortezomib as both preventative and treatment measure for GVHD [120,155].…”

Section: Bortezomibmentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after reduced intensity conditioning allogeneic stem cell transplantation for multiple myeloma

Cited by 60 publications

References 19 publications

Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the French Society of Bone Marrow and Cellular Therapy

Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the French Society of Bone Marrow and Cellular Therapy

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

State-of-the-art acute and chronic GVHD treatment

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