Bortezomib Induction and Maintenance in Patients with Newly Diagnosed Multiple Myeloma: Long-Term Follow-up of the HOVON-65/GMMG-HD4 Trial

Sonneveld, Pieter; Salwender, Hans-Juergen; Holt, Bronno van der; Jarari, Laila el; Bertsch, Uta; Blau, Igor Wolfgang; Zweegman, Sonja; Weisel, Katja; Vellenga, Edo; Pfreundschuh, Michael; Broijl, Annemiek; Scheid, Christof; Wittebol, Shulamiet; Bos, Gerard M.J.; Stevens-Kroef, M; Jauch, Anna; Potamianou, Anna; Hose, Dirk; Raymakers, Reinier; Schaafsme, Marinus; Kersten, Marie José; Kooy, Marinus van Marwijk; Duehrsen, Ulrich; Lindemann, Hans Walter; Brossart, Peter; Wijermans, Pierre W.; Lokhorst, Henk M.; Goldschmidt, Hartmut

doi:10.1182/blood.v126.23.27.27

Cited by 31 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From these references, 21 published articles deriving from 10 different RCT, with a total of 6474 patients, were eventually considered eligible for inclusion in meta-analysis. 11,12,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] One trial did not report HR data on OS. 32 and five on cardiac [28][29][30][31][32][33][34][35][36]38,39,43 AE.…”

Section: Study Selectionmentioning

confidence: 99%

“…We have arbitrarily allocated similar multidrug protocols based on their drug profile, resulting in 11 individual treatment groups: TT2- 35,38,43,45 (Bortezomib, Doxorubicin, and Dexamethasone), CRD (Cyclophosphamide, Lenalidomide, and Dexamethasone), 11,12 and Dex 44 (High Dose Dexamethasone). Network plots for all outcomes are presented in Figure 2.…”

Section: Treatment Group Allocation Network Assembling and Consismentioning

confidence: 99%

“…,33,36,39 All selected RCT reported HR data on PFS, nine reported frequency of gastrointestinal 27-44 AE, while eight reported data on CR 27-29,31-44 and ORR,27,29,30,[32][33][34][35][36][37][38][39][40][41][42][43][44] seven on hematological,27- 31,35,37,38,40-44 infectious,27,29,30,32,33,[35][36][37][38][39][40][41][42][43][44] and thrombotic[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] …”

mentioning

confidence: 99%

See 2 more Smart Citations

Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis

Sekine

Ziegelmann

Manica

et al. 2018

Hematological Oncology

View full text Add to dashboard Cite

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post-transplant results. Therefore, best frontline treatment for transplant-eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta-analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide-lenalidomide-dexamethasone) over TD-based (thalidomide-dexamethasone, HR = 0.76,0.62-0.90), VAD-based (HR = 0.71,0.52-0.90), and Z-Dex (idarubicin-dexamethasone, HR = 0.37,0.17-0.76) regimens. Concerning PFS, VTD (bortezomib-thalidomide-dexametasone) showed superior results when compared with TD-based (HR = 0.66,0.51-0.84), VAD-based (HR = 0.61,0.46-0.82), Z-Dex (HR = 0.42,0.22-0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41-0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide-only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide-doxorubicin-dexamethasone), neurological with PAD (bortezomib-doxorubicin-dexamethasone), infectious with Dex, hematological with Z-Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant-eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression-free survival, when compared with bortezomib/thalidomide protocols.

show abstract

Section: Study Selectionmentioning

confidence: 99%

Section: Treatment Group Allocation Network Assembling and Consismentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis

Sekine

Ziegelmann

Manica

et al. 2018

Hematological Oncology

View full text Add to dashboard Cite

show abstract

“…However, subgroups harboring the t (4;14) and +1q abnormalities did not benefit to such a degree, and the negative impact conferred by these abnormalities remained significant. Additional studies are required to determine whether or not patients with t(4;14) and +1q truly benefit from maintenance therapy with bortezomib [27]. The role of maintenance therapy in the context of the current treatment landscape remains a topic that must be further explored.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma

Sivaraj

Green

et al. 2017

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an inability to tolerate lenalidomide, or a previous history of another cancer.

show abstract

“…G-CSF alone mobilization was used in this trial. On the contrary, in the HOVON-65/GMMG-HD4 trial comparing bortezomib, adriamycin, dexamethasone (PAD) with VAD, all patients successfully collected stem cells for aHSCT and no impact of bortezomib on collection was observed [17,18]. Of note, chemomobilization with cyclophosphamide and adriamycin was used as the mobilization procedure.…”

Section: Introductionmentioning

confidence: 99%

VTD in comparison with VCD does not affect stem cell yields with G-CSF only mobilization

Škerget

Skopec

Sever

2020

Acta Haematologica Polonica

View full text Add to dashboard Cite

Triplet induction regimens are standard of care for newly diagnosed transplant eligible multiple myeloma patients. The combinations of bortezomib and dexamethasone with either cyclophosphamide (VCD) or thalidomide (VTD) are widely used. There are no data available on the impact of the two regimens on stem cell harvest by using G-CSF only mobilization. In this study, we retrospectively analyzed data from our national registry. The outcome measures were mobilization failure, CD34+ cell counts on collection day, number of apheresis procedures, and the number of collected cells. Overall, 72 patients were treated with either VCD or VTD. The mobilization failure rates were 7% and 9% (p = 0.771) and the total number of collected stem cells were 7.0 × 106 and 6.7 × 106 per kg body weight (p = 0.710) for VCD and VTD, respectively. We found no statistically significant difference between the treatment groups in the outcome measures. The addition of thalidomide to bortezomib and dexamethasone (VTD) does not adversely affect stem cell harvest in patients mobilized with G-CSF only.

show abstract

Bortezomib Induction and Maintenance in Patients with Newly Diagnosed Multiple Myeloma: Long-Term Follow-up of the HOVON-65/GMMG-HD4 Trial

Cited by 31 publications

References 0 publications

Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis

Frontline treatment for transplant‐eligible multiple myeloma: A 6474 patients network meta‐analysis

Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma

VTD in comparison with VCD does not affect stem cell yields with G-CSF only mobilization

Contact Info

Product

Resources

About