Long-term follow-up of subcutaneous versus intravenous bortezomib during induction therapy for newly diagnosed multiple myeloma treated within the GMMG-MM5 Phase III Trial

Leukemia ◽  
2021 ◽  
Author(s):  
Hans Salwender ◽  
Ahmet Elmaagacli ◽  
Maximilian Merz ◽  
Kaya Miah ◽  
Axel Benner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Long Term Follow Up

Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951

2013 ◽  
Vol 31 (3) ◽  
pp. 344-350 ◽  
Author(s):  
Martin J. van den Bent ◽  
Alba A. Brandes ◽  
Martin J.B. Taphoorn ◽  
Johan M. Kros ◽  
Mathilde C.M. Kouwenhoven ◽  
...  
Keyword(s):  
Methylation Status ◽  
Prognostic Significance ◽  
Phase Iii ◽  
Anaplastic Oligodendroglioma ◽  
Newly Diagnosed ◽  
Oligodendroglial Tumors ◽  
Mutational Status ◽  
Long Term Follow Up

Purpose Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). Patients and Methods Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. Results A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. Conclusion The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non–1p/19q-deleted tumors.

Intravenous Busulfan-Melphalan vs Melphalan as Preparative Regimen for Newly Diagnosed Multiple Myeloma: Long-Term Follow-Up of a Case-Control Study

2019 ◽  
Vol 19 (10) ◽  
pp. e287-e288
Author(s):  
Margarita Blanes ◽  
Jose Ignacio Lorenzo ◽  
Paz Ribas ◽  
Ana Jiménez ◽  
José David González ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Case Control Study ◽  
Case Control ◽  
Newly Diagnosed ◽  
Long Term Follow Up ◽  
Preparative Regimen ◽  
Control Study

Phase III Trial Of Bortezomib, Melphalan, and Prednisone (VMP) Versus Bortezomib, Thalidomide, and Prednisone (VTP) In Elderly Multiple Myeloma (MM) Patients: Update Follow-Up, Patterns Management Of First Relapse/Progression

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1973-1973 ◽  
Author(s):  
Aurelio Lopez ◽  
Marta Valero ◽  
Jose Ignacio Lorenzo ◽  
Maria-Victoria Mateos ◽  
Albert Oriol ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Induction Therapy ◽  
Phase Iii ◽  
Clinical Relapse ◽  
Newly Diagnosed ◽  
Front Line ◽  
Phase Iii Trial ◽  
Symptomatic Relapse ◽  
First Relapse

Abstract Background Initial results of the Spanish GEM2005mas65 phase III trial comparing VMP versus VTP as induction therapy in elderly patients with newly diagnosed MM did not show any difference in terms of OS or PFS. The purpose of this study was to update clinical results with a longer follow-up. Secondary objectives were to know the patterns of symptomatic relapse and response to therapy in patients previously exposed to novel agents. Methods GEM2005mas65 trial lasted from March, 2006, and October, 2008. Overall, 260 patients with untreated MM, 65 years and older, from 63 Spanish centres, were randomly assigned to receive six cycles of VMP (n=130) or VTP (n=130) as induction therapy followed by maintenance therapy with bortezomib plus prednisone (n=87) or bortezomib plus thalidomide (n=91). Results With a median follow-up of 53.2 months, median OS of the entire cohort of patients was 42.45 months. Median OS was 62 months in patients receiving VMP versus 42.6 months in patients receiving induction with VTP (P = 0.045) (Figure 1). No differences were observed in PFS, being 31 and 24.4 months in the VMP and VTP groups, respectively. At the time of the study, 167 patients had relapsed or progressed and 92 of them received some kind of post relapse treatment. Front-line therapy and clinical and biological characteristics at the time of relapse in this subgroup of patients are summarized in Table 1. Initial induction treatment consisted of VMP in 40 (43.4%) patients and VTP in 52 (56.5%) patients. Overall, after induction and maintenance therapy 66 (71.7%) patients had been exposed to bortezomib and thalidomide and 26 (28.2%) patients received bortezomib-based therapy without immunomodulatory agents before relapse. At symptomatic relapse, median age was 74 years (range 65-87) and 43 (46.7%) were male. Serum creatine level > 2 mg/dL was present in 11.9% of the patients and 4.3 % had hypercalcemia. Extramedullary disease and plasma cell leukemia was present in 17% and 4.4% of patients, respectively. Finally, severe bone disease was observed in 39 the patients. Management of relapse was very heterogeneous. Subsequent drugs used in first clinical relapse included lenalidamide combinations in 40 (43.4%) patients, bortezomib-based therapy in 19 (20.5%) patients, different chemotherapy combinations in 25 (27.1%) patients and bendamustine-prednisone in 2 (2.1%) patients. Six (6.5%) patients received only supportive at time of first relapse. Overall, 45 (52%) patients achieved partial response or better after rescue therapy. Response rates were higher after lenalidomide-based therapy (62.5%) when compared with bortezomib (42.1%) and conventional chemotherapy-based regimens (40.7%),although this difference did not translate into significant PFS advantage. After a median follow-up of 16.4 months (range 0-50.2) from clinical relapse,58 (63%) patients had died. Median PFS and OS were 10 (CI95%; 10.7-50.2) and 15.6 months (CI95%; 8.5-16.5%), respectively. In patients initially treated with VMP (n = 40) and VTP (n =52) median survival from start of subsequent therapy was 15.6 and 15.4 months, respectively. Among characteristics at relapse, only ISS stage had an impact on survival (P= 0.03).There was no difference in OS or PFS from front-line induction and/or maintenance therapies or salvage therapy. Conclusions This updated analysis of the GEM2005mas65trial shows a survival advantage of the VMP arm when compared with patients receiving VTP. Patterns of relapse were similar regardless previous induction and maintenance therapy. Finally, and when analyzing the subgroup of patients receiving active therapy at relapse, only ISS stage seemed to have a prognostic impact on OS. Group A: VMP, group B : VTD Disclosures: Mateos: Janssen, Celgene, Onyx, Millennium, Mundipharma: Honoraria. Oriol:Celgene: Consultancy. Off Label Use: Bendamustine, bortezomib and prednisone is a combination not approved for newly diagnosed myeloma patients.

Thalidomide / Dexamethasone (TD) Vs. Bortezomib (Velcade)â/Thalidomide / Dexamethasone (VTD) Vs. VBMCP/VBAD/Velcadeâ as Induction Regimens Prior Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): Results of a Phase III PETHEMA/GEM Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 130-130 ◽  
Author(s):  
Laura Rosiñol ◽  
Ma Teresa Cibeira ◽  
Joaquin Martinez ◽  
Maria Victoria Mateos ◽  
Albert Oriol ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Therapy ◽  
High Risk Group ◽  
Phase Iii ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Phase Iii Trial ◽  
Grade 3

Abstract Abstract 130 In April 2006, the Spanish Myeloma Group (PETHEMA/GEM) activated a randomized phase III trial comparing TD vs. VTD vs. VBMCP/VBAD/Velcadeâ in patients 65 years-old or younger with newly diagnosed symptomatic MM, followed by ASCT with MEL-200. The primary end points were response rate after induction and after ASCT and time to progression. TD consisted of thalidomide 200 mg daily (escalating doses in the first cycle) and dexamethasone 40 mg on days 1–4 and 9–12 at 4-week intervals for 6 cycles. The VTD regimen was identical to TD plus Velcade 1.3 mg/m2 on days 1,4,8,11 of each cycle. Combination chemotherapy plus Velcadeâ consisted of 4 cycles of VBMCP/VBAD on an alternating basis followed by 2 cycles of Velcadeâ (1.3 mg/m2 on days 1,4,8, and 11 every 3 weeks). The duration of the induction therapy was 24 weeks in all arms. From April 6, 2006 to August 5, 2009 the 390 planned patients entered the study. As of December 31, 2008, 305 patients (median age: 57 yrs, M: 156, F:149; IgG. 181, IgA: 71, light chain: 43, others: 10) entered the study and are the basis of the current analysis. Fifty-six (18%) patients had soft-tissue extramedullary plasmacytomas (EMP) and the stage according to the ISS was I in 39%, II in 41 %, III in 19 % and unknown in 1%. The prognostic factors, including cytogenetics, was similar in the 3 arms. Fifty-five (18%) patients had high-risk cytogenetics (t(4;14), t(14;16) and/or 17p deletion). Two-hundred and ninety-nine patients (TD:103, VTD: 99 and VBMCP/VBAD/Velcade®: 97) were evaluable for response and toxicity to induction therapy. The ≥ PR rate was 64%, 82% and 75% with TD, VTD and VBMCP/VBAD/Velcade®, respectively (p=NS). The IF negative CR rate was significantly higher with VTD (29%) and with VBMCP/VBAD/Velcade® (25%) than with TD (14%) (p=0.009 and p=0.04, respectively). Progressive disease (PD) was significantly higher with TD than with VTD (21% vs. 8%, p=0.009). In the overall series, PD was significanty higher in patients with EMP (34% vs. 12%, p=0.0002) with a significanty higher PD rate for TD as compared with VTD (40% vs. 14%, p=0.05). In patients with poor cytogenetics the CR rate was significantly higher with VTD than with TD (42% vs. 5%, p=0.009). In this high-risk group the PD rate was higher with TD (37%) and with VBMCP/VBAD/Velcade® (23%) than with VTD (0%) (p=0.009 and p=0.04, respectively). The incidence of thrombotic events ≥ grade 3 was higher in the TD arm (9% vs. 1% vs. 3%, p=0.07 and p=0.01) while ≥3 peripheral neuropathy was higher with VTD (14% vs. 0% and 1%, p<0.0001 and p=0.0003). Treatment was discontinued due to toxicity in 11 patients (TD: 3, VTD: 6, VBMCP/VBAD/Velcade®:2). Eight patients died during induction period (TD:5, VTD: 2, VBMCP/VBAD/Velcade®: 1) One-hundred seventy-seven patients were evaluable for response after ASCT. The post-ASCT CR rate with TD, VTD and VBMCP/VBAD/Velcade® was 40%, 59% and 48%, respectively, being significantly higher with VTD than with TD (p=0.05). The estimated overall survival at 2 years is 82% with no significant differences among the 3 arms. TTP and PFS were significantly shorter with TD (p=0.05 and p=0.012, respectively). In summary, VTD results in a higher pre- and post-ASCT CR rate as well as in a lower PD rate than TD, particularly in patients with high-risk cytogenetics or with EMP. The TTP and PFS are shorter with TD. Intermediate results are observed with VBMCP/VBAD/Velcade®. Longer follow-up is needed to establish whether or not these results will translate into a significantly different long-term outcome. Updated data will be presented at the meeting. Disclosures: Rosiñol: Janssen-Cilag: Honoraria; Celgene: Honoraria. Off Label Use: Thalidomide and bortezomib are not yet approved in Spain. Cibeira:Jansse-Cilag: Honoraria; Celgene: Honoraria. Mateos:Janssen-Cilag: Honoraria; Celgene: Honoraria. Oriol:Janssen-Cilag: Honoraria; Celgene: Honoraria. García-Laraña:Janssen-Cilag: Honoraria; Celgene: Honoraria. de la Rubia:Janssen-Cilag: Honoraria; Celgene: Honoraria. Sureda:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palomera:Janssen-Cilag: Honoraria; Celgene: Honoraria. Díaz-Mediavilla:Janssen-Cilag: Honoraria; Celgene: Honoraria. de Arriba:Janssen-Cilag: Honoraria; Celgene: Honoraria. Alegre:Janssen-Cilag: Honoraria; Celgene: Honoraria. Lahuerta:Janssen-Cilag: Honoraria; Celgene: Honoraria. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria. Blade:Janssen-Cilag: Honoraria; Celgene: Honoraria.

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