Subcutaneous bortezomib in newly diagnosed patients with multiple myeloma nontransplant eligible: Retrospective evaluation

Fuente, Felipe de Arriba de la; Durán, María Soledad; Álvarez, Miguel A.; Sanromán, Isabel López; Dios, Ana M S de; Tamayo, Rafael Ríos; García, Ricarda; González, Marta Sonia; Prieto, Elena; Bárez, Abelardo; Escalante, Fernando; Tejedor, Aurelia; Ballesteros, Mónica; Cabañas, Valentín; Capote, Francisco; Couto, Carmen; Garzón, Sebastián; González-Pardo, Miriam; Mateos, María-Victoria

doi:10.1053/j.seminhematol.2017.09.002

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…In the context of the VCD regimen, weekly delivery of bortezomib has been reported in transplant-eligible populations, 21 , 22 , 23 , 24 but there have only been a few small retrospective reports of a weekly VCD regimen for the initial treatment of older patients. 25 , 26 The schedule of VCD in our trial, using 4-weekly bortezomib doses in a 5-week cycle, proved highly tolerable despite the older and frail population. Approximately 80% of patients in the VCDD arm completed the planned 9 cycles of induction, with an all-grade peripheral neuropathy rate of 28% and no grade 3 or 4 events.…”

Section: Discussionmentioning

confidence: 82%

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16

Mollee,

Reynolds,

Janowski

et al. 2024

Blood Advances

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In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard of care regimens. In a randomized trial, we tested whether similar improvements would be seen when daratumumab was added to the bortezomib, cyclophosphamide and dexamethasone (VCD) regimen. Non-transplant eligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). 121 patients were randomized, 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the two arms. The median PFS was 16.8m (95%CI 15.3 - 21.7m) and 25.8m (95%CI 19.9 - 33.5) in the VCD and VCDD arms, respectively (HR 0.67, log-rank test p=0.066). In a pre-planned analysis, the estimated PFS at fixed time-points post-randomization demonstrated significantly improved PFS for the daratumumab containing arm from 18 months onwards. The proportions of patients who were progression free at the following time points were: 18 months, 48% vs 68% (p=0.0002); 24 months, 36% vs 52% (p=0.0001); and 30 months, 27% vs 41% (p<0.0001) in the VCD and VCDD arms, respectively. The best overall response and VGPR rate were significantly better in the daratumumab arm (65% vs 86%, p=0.007 and 28% vs 52%, p=0.009) for the VCD and VCDD arms, respectively. Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of non-transplant eligible patients with myeloma. Australian and New Zealand Clinical Trials Registry (ACTRN12617000202369). https://www.anzctr.org.au/

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Section: Discussionmentioning

confidence: 82%

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16

Mollee,

Reynolds,

Janowski

et al. 2024

Blood Advances

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“…Heterogeneity analyses found that the introduction of the study resulted in moderate heterogeneity (I 2 = 65%) in the outcome of any grade of PN. This may be attributed to the vague grouping method in this study.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Once‐Weekly versus Twice‐Weekly Bortezomib in Patients with Hematologic Malignancies: A Meta‐analysis with Trial Sequential Analysis

Zhou

Zhuang

et al. 2019

Pharmacotherapy

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STUDY OBJECTIVE To compare the efficacy and safety of once-weekly and twice-weekly bortezomib therapy in patients with hematologic malignancies. DESIGN Meta-analysis of 13 clinical or randomized controlled trials, with trial sequential analysis (TSA). PATIENTS A total of 1567 patients with hematologic malignancies who received either once-weekly or twice-weekly bortezomib therapy. MEASUREMENTS AND MAIN RESULTS We conducted a comprehensive literature search of the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis was conducted to calculate the pooled effect size; TSA was performed to assess the reliability of the pooled results. The pooled risk ratio (RR) for the overall response rate (ORR) was 1.00 (95% confidence interval [CI] 0.77-1.29, p=0.99), indicating no significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. TSA showed that the cumulative Z-curve of the ORR entered the futility area, implying that reliable evidence was obtained for this pooled result. The pooled RR for any grade of peripheral neuropathy was 0.48 (95% CI 0.26-0.88, p=0.02); however, the TSA plot revealed that there was insufficient evidence for this result. The pooled RR for peripheral neuropathy grade 3 or higher was 0.21 (95% CI 0.13-0.34, p<0.00001), and reliable evidence was obtained according to TSA. Regarding the other toxicities, including anemia, thrombocytopenia, neutropenia, infection, diarrhea, constipation, nausea, vomiting, and fatigue, we did not find any significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. CONCLUSION Compared with twice-weekly bortezomib, once-weekly bortezomib had a comparable ORR and a probable lower incidence of peripheral neuropathy. More clinical trials are needed to draw a conclusion regarding the difference in peripheral neuropathy between the two groups because of the insufficient evidence detected by TSA and the inconsistent results among subgroups.

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“…In this study we focused on developing BTZ-dependent therapeutic strategies for glioblastoma in the context of OV therapies, but our mathematical model can be applied to other types of cancers. For instance, therapeutic effects of BTZ were studied in colon [115,116], prostate [117,118], breast [119,120], lung [121,122], melanoma [123,124], ovarian [20,125,126], myeloma [25,127,128], head and neck [20] cancers, EBV-associated lymphomas [129], hepatocellular carcinoma [130], and glioma [20,21]. Various types of OVs have been studied in combination with BTZ, including reovirus [131], HSV-1 [20,21,132], adenovirus [133] and VSV [134].…”

Section: Discussionmentioning

confidence: 99%

“…BTZ induces apoptosis by inhibiting the phosphorylation of IκB protein, thus inhibiting NF-κB activity [22,23]. While it is used as a single agent or in combination with other radio-/chemo-agents for many cancers, including multiple myeloma, ovarian cancer, and head and neck cancers, different combination strategies are being developed for better efficacy [24,25,26,27] in these and other tumor types.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Bortezomib-OV Therapy and Anti-Invasive Strategies in Glioblastoma: A Mathematical Model

Kim

Lee

et al. 2019

Cancers

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It is well-known that the tumor microenvironment (TME) plays an important role in the regulation of tumor growth and the efficacy of anti-tumor therapies. Recent studies have demonstrated the potential of combination therapies, using oncolytic viruses (OVs) in conjunction with proteosome inhibitors for the treatment of glioblastoma, but the role of the TME in such therapies has not been studied. In this paper, we develop a mathematical model for combination therapies based on the proteosome inhibitor bortezomib and the oncolytic herpes simplex virus (oHSV), with the goal of understanding their roles in bortezomib-induced endoplasmic reticulum (ER) stress, and how the balance between apoptosis and necroptosis is affected by the treatment protocol. We show that the TME plays a significant role in anti-tumor efficacy in OV combination therapy, and illustrate the effect of different spatial patterns of OV injection. The results illustrate a possible phenotypic switch within tumor populations in a given microenvironment, and suggest new anti-invasion therapies.

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Subcutaneous bortezomib in newly diagnosed patients with multiple myeloma nontransplant eligible: Retrospective evaluation

Cited by 8 publications

References 18 publications

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for transplant-ineligible myeloma: AMaRC 03-16

Efficacy and Safety of Once‐Weekly versus Twice‐Weekly Bortezomib in Patients with Hematologic Malignancies: A Meta‐analysis with Trial Sequential Analysis

Synergistic Effects of Bortezomib-OV Therapy and Anti-Invasive Strategies in Glioblastoma: A Mathematical Model

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