The role of novel agents for consolidation after autologous transplantation in newly diagnosed multiple myeloma: a systematic review

Gagelmann, Nico

doi:10.1007/s00277-020-04316-8

Cited by 4 publications

(4 citation statements)

References 47 publications

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“…2021, 11, x FOR PEER REVIEW 10 of 16 the contribution of altered calcium intracellular homeostasis due to mitochondrial dysfunction and for altered sodium/potassium conductance secondary to Na + -K + -ATPase dysfunction has also been confirmed [88,89]. Carfilzomib, a second-generation proteasome inhibitor approved for multiple myeloma treatment, substantially mirrors the bortezomib toxicity profile although it has been reported to have overall less neurotoxicity [77].…”

Section: Chemotherapy-induced Neurotoxicity (Cipn)mentioning

confidence: 99%

“…Thalidomide, a glutamic acid derivative, is employed in hematological conditions including multiple myeloma for its anti-angiogenic, immunomodulatory, and anti-inflammatory properties [77]. The mechanisms of thalidomide-induced neuropathy are still unclear, but different hypothesis have been suggested, including microvascular damage due to the anti-angiogenic properties of the drug, direct toxic effect [78], or inhibition of NF-kB, an essential regulator in the nerve growth factor-mediated effects on the survival of sensory neurons [79].…”

Section: Chemotherapy-induced Neurotoxicity (Cipn)mentioning

confidence: 99%

“…Proteasome inhibitors bortezomib and carfilzomib are currently included in the treatment protocols for multiple myeloma, WM, and mantle cell lymphoma. Moreover, bortezomib-based regimens are an effective and safe treatment option also in patients with POEMS syndrome [77,84]. Bortezomib bears a severe neurotoxicity potential, with the vast majority of patients presenting with an axonal sensory-motor peripheral neuropathy and prominent neuropathic pain [85], and only a minority showing a predominant motor involvement and demyelinating features at neurophysiology and nerve biopsy [86].…”

Section: Chemotherapy-induced Neurotoxicity (Cipn)mentioning

confidence: 99%

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Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

et al. 2021

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Despite the introduction of non-invasive techniques in the study of peripheral neuropathies, sural nerve biopsy remains the gold standard for the diagnosis of several neuropathies, including vasculitic neuropathy and neurolymphomatosis. Besides its diagnostic role, sural nerve biopsy has helped to shed light on the pathogenic mechanisms of different neuropathies. In the present review, we discuss how pathological findings helped understand the mechanisms of polyneuropathies complicating hematological diseases.

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Section: Chemotherapy-induced Neurotoxicity (Cipn)mentioning

confidence: 99%

Section: Chemotherapy-induced Neurotoxicity (Cipn)mentioning

confidence: 99%

Section: Chemotherapy-induced Neurotoxicity (Cipn)mentioning

confidence: 99%

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Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

et al. 2021

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“…Although consolidation therapy directly after transplantation has shown deeper responses and improved long‐term outcome, 6 this strategy is still lacking approval. In contrast, maintenance therapy is recommended for all patients 7 .…”

Section: Introductionmentioning

confidence: 99%

Impact of newly diagnosed extramedullary myeloma on outcome after first autograft followed by maintenance: A CMWP‐EBMT study

Gagelmann

Eikema

Köster

et al. 2023

European J of Haematology

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Background No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy. Methods We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib. Results The median follow‐up from maintenance start was 44 months. Three‐year progression‐free survival (PFS) was 52% (48%–57%) for no EMD, 56% (44%–69%) for paraskeletal involvement, and 45% (22%–68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three‐year overall survival (OS) was 81% (77%–84%), 88% (80%–96%), and 68% (47%–89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD. Conclusion Lenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start.

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Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Kostroma

Sidorova

Semenova

et al. 2021

Клиническая онкогематология

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Aim. To assess the rate of cases without antitumor response quality improvement after high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). To assess the rate of allelic variants of IL1B, IL6, IL10, TNF genes and the status of hematopoietic niche cells as potential predictors of au-to-HSCT efficacy. Materials & Methods. A retrospective analysis was based on the data of 84 MM patients who received 112 auto-HSCTs, including 84 first and 28 repeated courses. Response variants were estimated according to IWG criteria. Molecular profiling of IL1B, IL6, IL10, and TNF genes was performed using polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length polymorphism of PCR products. To analyze the status of hematopoietic niche cells histological, immunohistochemical, and morphometric methods were applied. Results. The first auto-HSCT yielded response quality improvement in 29 (54.7 %) out of 84 patients. The rate of complete response was significantly higher in patients who showed very good partial response before HDCT with au-to-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (p = 0.005). No differences were identified in the groups of patients with other clinical and hematological parameters. After the second auto-HSCT in 4 out of 6 patients with PR the response variant did not change. A significant decrease of MM activity was associated with IL6 (-174С) mutant allele carrier status of 81.3 % vs. 41.6 % in the group with the unchanged response variant (р = 0.05). Response quality improvement was also related to a large number of cells on the endosteum in histological specimens of bone marrow (p = 0.038). Conclusion. The carrier status of IL6 (-174С) pathologic allele as well as the number of cells on the endosteum in histological specimens of bone marrow can be regarded as predictors of response quality improvement or lack thereof in MM patients after auto-HSCT.

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The role of novel agents for consolidation after autologous transplantation in newly diagnosed multiple myeloma: a systematic review

Cited by 4 publications

References 47 publications

Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

Mechanisms of Nerve Damage in Neuropathies Associated with Hematological Diseases: Lesson from Nerve Biopsies

Impact of newly diagnosed extramedullary myeloma on outcome after first autograft followed by maintenance: A CMWP‐EBMT study

Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

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