Targeted treatments to improve stem cell outcome: old and new drugs

Raab, Marc-Steffen; Breitkreutz, Iris; Anderson, Kenneth C.

doi:10.1038/sj.bmt.1705829

Cited by 4 publications

(3 citation statements)

References 67 publications

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“…In fact, bone involvement is present in 70-100% of patients with MM and is associated with pain and skeletal-related complications, such as fractures and hypercalcemia. Despite being an incurable disease, considerable improvements in the prognosis of MM have been registered since the introduction of highdose chemotherapy with autologous hematopoietic support [1][2][3][4], newer biologically targeted agents, and the use of zoledronic acid [5]. Despite this recent increase in treatment options, a significant proportion of patients will eventually develop symptoms of bone progression during the course of the disease [6].…”

Section: Introductionmentioning

confidence: 99%

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Anselmetti

Manca

Montemurro

et al. 2011

Cardiovasc Intervent Radiol

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Purpose Percutaneous vertebroplasty (PV) is a minimally invasive procedure involving the injection of bone cement within a collapsed vertebral body. Although this procedure was demonstrated to be effective in osteoporosis and metastases, few studies have been reported in cases of multiple myeloma (MM). We prospectively evaluated the safety and efficacy of PV in the treatment of vertebral compression fractures (VCFs) resulting from MM. Materials and Methods PV was performed in 106 consecutive MM patients who had back pain due to VCFs, the treatment of which had failed conservative therapies. Follow-up (28.2 ± 12.1 months) was evaluated at 7 and 15 days as well as at 1, 3, 6, 12, 18, and every 6 months after PV. Visual analog scale (VAS) pain score, opioid use, external brace support, and Oswestry Disability Index (ODI) score were recorded. Results The median pretreatment VAS score of 9 (range 4-10) significantly (P \ 0.001) decreased to 1 (range 0-9) after PV. Median pre-ODI values of 82% (range 36-89%) significantly improved to 7% (range 0-82%) (P \ 0.001). Differences in pretreatment and posttreatment use of analgesic drug were statistically significant (P \ 0.001). The majority of patients (70 of 81; 86%) did not use an external brace after PV (P \ 0.001).

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Section: Introductionmentioning

confidence: 99%

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Anselmetti

Manca

Montemurro

et al. 2011

Cardiovasc Intervent Radiol

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“…Ultimately, the most profound effects have been observed against cell lines derived from multiple myeloma and other hematologic malignancies [11–19]. Bortezomib was originally approved for the treatment of recurrent multiple myeloma in May 2003 and has been subsequently approved for treating newly diagnosed multiple myeloma and recurrent mantle cell lymphoma [20–25]. …”

Section: Introductionmentioning

confidence: 99%

Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma

Phuphanich

Supko²,

Carson³

et al. 2010

J Neurooncol

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Bortezomib selectively binds and inhibits the 20S proteasome enzyme’s active sites. This study was conducted to determine the side effects and maximum tolerated dose (MTD) of bortezomib in patients with recurrent malignant glioma. Separate dose escalations were conducted in patients taking or not taking enzyme-inducing anti-seizure drugs (+/−EIASD). The starting dose in both groups was 0.9 mg/m2 intravenously twice weekly for the first three of each 4 week cycle. Imaging assessment of response was carried out and Plasma 20S proteasome activity inhibition and imaging was conducted to monitor efficacy. The 66 patients enrolled had a median age of 51 years, median KPS of 90%, and 77% had glioblastoma multiforme. The MTD in the −EIASD group was 1.70 mg/m2 based on grade 3 thrombocytopenia, sensory neuropathy and fatigue. In the +EIASD group escalation was terminated at 2.5 mg/m2 without meeting meet the MTD criteria. However, proteasome inhibition in this group did not change at doses above 1.90 mg/m2 suggesting that further escalations would be unlikely to increase a biologic effect. Mean proteasome inhibition plateaued in +EIASD patients receiving 2.1 mg/m2 of bortezomib at 77 ± 12% and in −EIASD patients treated with a dose of 1.7 mg/m2 at 79 ± 6%. Two partial responses were observed. This study determined that EIASDs effect the MTD of bortezomib and the dose required for maximal inhibition of whole blood 20S proteasome. Some evidence of clinical activity was noted in this phase I study in patients with recurrent high grade gliomas.

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“…Cytokine-induced osteoclastic bone resorption is reported in 70-100% of multiple myeloma (MM) patients, 1 resulting in back pain, vertebral fractures (55-70% of MM patients), and neurological deficits from spinal cord or nerve root impingement (up to 30% of MM patients). [2][3][4][5] Although an incurable disease with an ageadjusted incidence of 6 per 100 000 annually and a 45% 5-year survival rate, 2,6 MM prognosis has improved with the introduction of high-dose chemotherapy alongside autologous hematopoietic support, [7][8][9][10] new biologically targeted agents, and the use of zoledronic acid. 11 As patients with MM are living longer, painful complications from osteolytic bone lesions are becoming an increasingly impactful and prevalent clinical concern on their quality of life.…”

Section: Introductionmentioning

confidence: 99%

Evaluating Treatment Strategies for Spinal Lesions in Multiple Myeloma: A Review of the Literature

et al. 2018

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Background: Vertebral disease is a major cause of morbidity in 70% of patients diagnosed with multiple myeloma (MM). Associated osteolytic lesions and vertebral fractures are well documented in causing debilitating pain, functional restrictions, spinal deformity, and cord compression. Currently, treatment modalities for refractory MM spinal pain include systemic therapy, radiotherapy, cementoplasty (vertebroplasty/kyphoplasty), and radio frequency ablation. Our objectives were to report on the efficacy of existing treatments for MM patients with refractory spinal pain, to determine if a standardized treatment algorithm has been described, and to set the foundation upon which future prospective studies can be designed. Methods: A systematic search of the PubMed database was performed for studies relevant to the treatment of vertebral disease in MM patients. A multitude of search terms in various combinations were used, including but not limited to: ''vertebroplasty,'' ''kyphoplasty,'' ''radiation,'' ''multiple myeloma,'' ''radiotherapy,'' and ''radiosurgery.'' Results: Our preliminary search resulted in 219 articles, which subsequently resulted in 19 papers following abstract, title, full-text, and bibliography review. These papers were then grouped by treatment modality: radiotherapy, cementoplasty, or combination therapy. Significant pain and functional score improvement across all treatment modalities was found in the majority of the literature. While complications of treatment occurred, few were noted to be clinically significant. Conclusions: Treatment options-radiotherapy and/or cementoplasty-for vertebral lesions and pathologic fractures in MM patients demonstrate significant radiographic and clinical improvement. However, there is no consensus in the literature as to the optimal treatment modality as a result of a limited number of studies reporting headto-head comparisons. One study did find significantly improved pain and functional scores with preserved vertebral height in favor of kyphoplasty over radiotherapy. When not contraindicated, we advocate for some form of cementoplasty. Further prospective studies are required before implementation of a standardized treatment protocol. Level of Evidence: 5.

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Targeted treatments to improve stem cell outcome: old and new drugs

Cited by 4 publications

References 67 publications

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Percutaneous Vertebroplasty in Multiple Myeloma: Prospective Long-Term Follow-Up in 106 Consecutive Patients

Phase 1 clinical trial of bortezomib in adults with recurrent malignant glioma

Evaluating Treatment Strategies for Spinal Lesions in Multiple Myeloma: A Review of the Literature

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