In the era of novel therapeutic agents for multiple myeloma mm, both the significance of achieving the plateau phase and the efficacy of subsequent maintenance therapy remain unclear. The european intergroup trial of the european myeloma network emn emn02ho95 mm protocol. In patients with recently diagnosed multiple myeloma, the hovon 50 phase 3 trial showed improved eventfree survival for thalidomidecontaining induction and maintenance regimens in conjunction with highdose melphalan and autologous stem cell transplantation autosct after a median of 52 months of followup, by comparison with regimens containing classical cytotoxic drugs. Bortezomib maintenance statistically significantly improved both. Our result showed a comparable upgrade in response of 19% in patients receiving bortezomib maintenance.
It is established that the use of newer, more active agents as part of induction regimens, such as bortezomib, 3, 4 thalidomide, 5, 6 and lenalidomide, 4, 79 improve the orr and the complete response cr rate before hdt and asct, but it is not clear from current phase 3 trials whether the impact of achieving a better response before and after. Bortezomibmelphalanprednisonethalidomide followed by maintenance with bortezomibthalidomide compared with bortezomibmelphalanprednisone for initial. Velcade bortezomib dose, indications, adverse effects. The chemical name for bortezomib, the monomeric boronic acid, is 1r3methyl12s1oxo3phenyl2pyrazinylcarbonyl aminopropylaminobutyl boronic acid. Immunochemotherapy followed by autologous transplant asct in calgballiance 59909 achieved a median progressionfree survival pfs in mantle cell lymphoma mcl of 5 years, but late recurrences occurred. The hovon gmmghd4 phase iii randomized control trial also explored the use of bortezomib as induction therapy but in addition looked at its role in the maintenance setting. Bortezomib for induction therapy in multiple myeloma before high dose chemotherapy and autologous stem cell transplantation. At the time of analysis of this microarray data an appropriate tool. Additional information is available in the individual branded drug profile pages. Bortezomib induction and maintenance treatment in patients. How to use bortezomib solution, reconstituted recon soln this medication is given by injection into a vein or under the skin by a health care professional. The primary endpoint of the fourth trial, the hovon. Os was improved with bortezomib maintenance compared to thalidomide maintenance sonneveld et al, 2012.
Lenalidomide vs bortezomib maintenance choice post. Analysis of the gene and snp sets for peripheral neuropathy associated with bortezomib and vincristine was done by use of ingenuity pathway analysis software version 8. Bortezomib based regimens are widely used as induction therapy for multiple myeloma mm. The hovon gmmghd4 phase iii randomized control trial also explored the use of. Palumbo a, bringhen s, rossi d, et al, bortezomib, melphalan, prednisone and thalidomide vmpt followed by maintenance with bortezomib and thalidomide for initial treatment of elderly multiple myeloma patients, blood, 2009, 11422. Pdf imwg consensus on maintenance therapy in multiple myeloma. A phase ii trial of smalldose bortezomib, lenalidomide and. In the present study, we evaluated the efficacy and safety of bortezomib maintenance therapy biweekly for 1 year in transplantineligible mm patients who plateaued after bortezomibbased induction therapy.
Disease response improved while on maintenance in 34% n 32 with lenalidomide and 38% n 23 with bortezomib table 2. Bortezomib is an important part of current antimyeloma therapy. Bortezomib maintenance therapy in newly diagnosed patients with mantle cell lymphoma, responsive on rituximab combined with chop and high dose arac and after beam with auto psct rescue. Bortezomibbased consolidationmaintenance therapy led to a trend toward. Therefore, proactive management of peripheral neuropathy and. Velcade bortezomib dosing, indications, interactions. Pharmaceutical benefits scheme pbs bortezomib, powder. Efficacy and safety of bortezomib maintenance in patients with newly. Bortezomibbased consolidation or maintenance therapy for. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma. Sonneveld and colleagues reported the longterm followup results of the hovon 65gmmghd4 trial, which had previously demonstrated bortezomibbased induction and maintenance regimens followed by hdm and asct significantly improved survival outcomes in transplanteligible patients with newly diagnosed mm compared with standard. The following organisations accepted the invitation to participate in this appraisal as consultees and commentators. Additionally, for highrisk myeloma patients two or more drugs may be suggested as maintenance therapy.
The joint hovon gmmg trial randomized 6 patients to bortezomib doxorubicindexamethasone pad or vad induction therapy followed by single or double asct. In the trial, 827 patients were randomized to different. Outcomes of maintenance therapy with bortezomib after. Consolidationmaintenance therapy induces deep remission in. Bortezomib induction and maintenance treatment in patients with. Bortezomib maintenance in high risk dlbcl full text view. Data sources include ibm watson micromedex updated 4 may 2020, cerner multum updated 4 may 2020. Maintenance with bortezomib was initiated between 60 and 90 days after asct as a single agent 1. Unlike lenalidomide, the role of bortezomib in consolidation and. The joint hovon gmmg trial randomized 6 patients to bortezomibdoxorubicindexamethasone pad or vad induction therapy followed by single or double asct. Efficacy and safety of bortezomib maintenance in patients. Pomalidomide combined with carfilzomib and dexamethasone pcd for induction and consolidation followed by pomalidomide combined with dexamethason vs pomalidomide maintenance for patients with multiple myeloma in progression after prior 1st line treatment with lenalidomide and bortezomib. In this study, patients who received up to 3 years of maintenance therapy starting 3 months after asct with bortezomib 1. Carfilzomib versus bortezomib in multiple myeloma saturday, april 1, 2017 at the 16th international myeloma workshop imw, two clinical trials of patients with newly diagnosed and relapsedrefractory multiple.
The pfs at 2 years was higher in the group that received maintenance with bortezomib plus thalidomide versus thalidomide versus interferon alpha 78% versus 63% versus 49%, respectively. Additionally, a phase 2 study has evaluated intensive bortezomib based triplet therapy as postasct maintenance in elderly patients, including 40% with highrisk disease, with promising early. Unlike lenalidomide, the role of bortezomib in consolidation and maintenance therapy for mm is less clear. The joint hovongmmg trial randomized 6 patients to. Autologous transplantation and maintenance therapy in. Maintenance therapy in multiple myeloma prerna mewawalla. Erasmus mc cancer institute, clinical trial center hs423 p. Listing a study does not mean it has been evaluated by the u.
In cycles 5 to 9, bortezomib is administered once weekly on days 1, 8, 22 and 29. Bortezomib for induction therapy in multiple myeloma. Combination therapy with bortezomib, continuous low. Mechanisms of peripheral neuropathy associated with. There are three patents protecting this compound and one paragraph iv challenge. In one study, patients received stem cell transplant with lenalidomide, bortezomib and dexamethasone for 3. The safety of bortezomib for the treatment of multiple. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study.
In the hovon 65 trialgmmghd4, a randomized phase iii trial was undertaken sonneveld et al. This study is registered as an international standard randomised controlled trial, number isrctn64455289. Bortezomib maintenance in high risk dlbcl borma the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Velcade as maintenance treatment in patients with multiple. Vrd consolidation and lenalidomide maintenance in patients with newly diagnosed.
Bortezomib, lenalidomide, and dexamethasone vrd followed. Standard schedule or maintenance schedule of once weekly for 4 weeks days 1, 8, 15, and 22 followed by a day rest period days 23 to 35 retreatment indicated for retreatment of adults with multiple myeloma who had previously responded to bortezomib and relapsed at least 6 months following completion of. Bortezomib before and after highdose therapy the long. One randomized trial from europe hovon 65 gmmghd4 bortezomib, doxorubicin, dex pad bortezomib maintenance vincristine, doxorubicin, dex vad thalidomide maintenance pfs and overall survival advantage in the bortezomib containing arm, unclear if this due to induction or maintenance. Hovon 65gmmghd4 randomized phase iii trial comparing bortezomib, doxorubicin, dexamethasone pad vs vad followed by highdose melphalan hdm and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma mm. Bortezomib has shown specific benefit for highrisk patients with kidney issues or deletion 17p in the european hovon 65gmmg study. Imwg consensus on maintenance therapy in multiple myeloma. Generic bortezomib inn equivalents, drug patent and. Hovon 65 gmmghd4 randomized phase iii trial comparing bortezomib, doxorubicin, dexamethasone pad vs vad followed by highdose melphalan hdm and maintenance bortezomib or thalidomide in patients with newly diagnosed multiple myeloma abstract. Maintenance therapy with subcutaneous bortezomib full.
Our study demonstrates that combination therapy with bortezomib, continuous low. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Maintenance therapy with subcutaneous bortezomib the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Copyright 2020 dove press ltd software development by.
Posttransplantation maintenance with bortezomib has also been evaluated. Staying on myeloma maintenance therapy how long and. The hovon trial compared bortezomib versus thalidomide as maintenance therapy after ahct for 2 years 34, 35 and showed that bortezomib maintenance prolonged pfs. In cycles 1 to 4, bortezomib is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32. Bortezomib induction and maintenance treatment in patients with newly.
Bortezomib maintenance therapy in transplantineligible. Analyses were performed using sas software, version 8. Melphalan 9 mgm2 and prednisone 60 mgm2 are both given orally on days 1, 2, 3 and 4 of the first week of each cycle. All analyses were conducted using graphpad prism version 5. Bortezomib induction, reducedintensity transplantation. Results of the randomized phase iii hovon 65 gmmghd4 trial pieter sonneveld, ingo g. Bortezomibbased consolidation or maintenance therapy for multiple. We evaluated tolerability and efficacy of adding posttransplant bortezomib consolidation bc or maintenance bm to this regimen in calgballiance 50403, a randomized phase ii trial. Median time to best response after maintenance initiation was 11. Purpose singlecycle melphalan 200 mgm2 and autologous hematopoietic cell transplantation ahct followed by lenalidomide len maintenance have improved progressionfree survival pfs and overall survival os for transplantationeligible patients with multiple myeloma mm. The use of bortezomib as frontline highdose therapy for multiple myeloma mm patients receiving highdose melphalan hdm followed by autologous stem cell transplantation asct, has been established by the dutchbelgian cooperative trial group for hematology and oncology group65germanspeaking myeloma multicenter group hd4 hovon 65gmmghd4. Maintenance treatment and survival in patients with. Primary therapy with single agent bortezomib as induction, maintenance and reinduction in patients with highrisk myeloma. Iv bortezomib maintenance was used in hovon65 phase iii study, following.
Updated results of the hovon 65gmmghd4 trial suggested that the negative effect of del17 was abrogated by bortezomibbased induction and maintenance, whereas there was only a trend for improved os in patients with t4. Full text update on the optimal use of bortezomib in the. Results of the randomized phase iii hovon 65 gmmghd4 trial. This study, which had previously demonstrated an advantage to bortezomib with doxorubicindex induction therapy followed by bortezomib maintenance versus vincristine with doxorubicindex followed by thalidomide maintenance, continues to.
A randomized phase iii study to compare bortezomib, melphalan, prednisone vmp with high dose melphalan followed by bortezomib, lenalidomide, dexamethasone vrd consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma. Full text update on the optimal use of bortezomib in the treatment of. In the phase iii hovon 65gmmghd4 trial, bortezomibbased treatment before and after asct showed a pfs advantage compared with classical cytotoxic induction therapy followed by postasct thalidomide maintenance goldschmidt et al. As for supplementary specification, newly developed grade 34 pn occurred in 8% of patients during thalidomide maintenance and 5% of patients during bortezomib in hovon 65gmmghd4 trial, and for vmptvt arm in the study of palumbo et al. Protocol dsmm viii is a multicenter, openlabel study evaluating the safety and tolerability, as well as the efficacy, of maintenance treatment with velcade bortezomib in patients with multiple myeloma with detectable disease activity following tandem high. Autologous transplantation, consolidation, and maintenance. Bortezomibbased regimens are widely used as induction therapy for multiple myeloma mm. We designed a prospective, randomized, phase iii study to test additional interventions to improve pfs by comparing. Bortezomib is the generic ingredient in two branded drugs marketed by millennium pharms, dr reddys labs ltd, fresenius kabi usa, and hospira inc, and is included in four ndas. Another important upfront trial hovon 65gmmghd4 reported more followup at ash. Results of the randomized phase iii hovon 65gmmghd4 trial article jul 2012.
1126 1156 648 675 356 1519 1458 1166 1328 247 18 641 1631 162 1541 56 1023 99 1021 915 1514 1249 1070 1397 1332 328 783 95 282 1476 405 790 215 572 1071 162 556 1357 1076 1457