Filter and export

Publications

What is a Publication?
10 Publications visible to you, out of a total of 10
Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study.

Abstract (Expand)

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate … of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.

Authors: A. Hochhaus, G. Rosti, N. C. Cross, J. L. Steegmann, P. le Coutre, G. Ossenkoppele, L. Petrov, T. Masszi, A. Hellmann, L. Griskevicius, W. Wiktor-Jedrzejczak, D. Rea, D. Coriu, T. H. Brummendorf, K. Porkka, G. Saglio, G. Gastl, M. C. Muller, P. Schuld, P. Di Matteo, A. Pellegrino, L. Dezzani, F. X. Mahon, M. Baccarani, F. J. Giles

Date Published: 7th Oct 2015

Publication Type: Journal

Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma.

Abstract (Expand)

We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial … response rates or better (⩾VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to ⩾VGPR rates (37.0 versus 34.3%, P=0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P=0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ⩾2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (⩾3 degrees ) occurred more frequently in the VCD arm (35.2% versus 11.3%, P<0.001). Neuropathy rates (⩾2 degrees ) were higher in the PAd group (14.9 versus 8.4%, P=0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P=0.04 and 2.8 versus 0.4%, P=0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ⩾VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.

Authors: E. K. Mai, U. Bertsch, J. Durig, C. Kunz, M. Haenel, I. W. Blau, M. Munder, A. Jauch, B. Schurich, T. Hielscher, M. Merz, B. Huegle-Doerr, A. Seckinger, D. Hose, J. Hillengass, M. S. Raab, K. Neben, H. W. Lindemann, M. Zeis, C. Gerecke, I. G. Schmidt-Wolf, K. Weisel, C. Scheid, H. Salwender, H. Goldschmidt

Date Published: 20th Mar 2015

Publication Type: Journal

GMMG MM5 Trial In Newly Diagnosed Multiple Myeloma To Evaluate PAd Vs VCD Induction Prior To High Dose Treatment Followed By Lenalidomide Consolidation and Maintenance – Final Analysis On Induction Therapy

Abstract (Expand)

Abstract Background The MM5 phase III trial of the German-Speaking Myeloma Multicenter Group (GMMG) was designed to address two independent primary objectives: 1.) demonstration of non-inferiority of …objectives: 1.) demonstration of non-inferiority of VCD (bortezomib, cyclophosphamide, dexamethasone) induction compared to PAd (bortezomib, adriamycin, dexamethasone) induction therapy with respect to response rate (very good partial response or better). 2.) determination of the best of four treatment strategies with respect to progression-free survival (PFS). The four treatment strategies were defined by PAd vs. VCD induction treatment, high dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) as well as consolidation and maintenance treatment with lenalidomide for 2 years vs. lenalidomide until complete response (CR). Methods 504 patients were included in the trial between July 2010 and October 2012. A non-inferiority analysis of VCD compared to PAd with respect to response rates after induction treatment with a non-inferiority margin of 10% for the difference in response rates (VGPR and better; first primary endpoint) and a safety analysis were performed. During the induction phase the patients were treated with 3 cycles of PAd or VCD. PAd was dosed as bortezomib 1.3 mg/m2, days 1, 4, 8, 11, doxorubicin 9 mg/m2, days 1-4, dexamethasone 20 mg, days 1-4, 9-12, 17-20 (repeated every 28 days). VCD consisted of bortezomib 1.3 mg/m2, days 1, 4, 8, 11, cyclophosphamide 900 mg/m2 day 1, dexamethasone 40 mg, days 1-2, 4-5, 8-9, 11-12 (repeated every 21 days). The route of administration for bortezomib was changed from intravenously to subcutaneously in all study arms by a protocol amendment in February 2012 after inclusion of 314 patients. The non-inferiority analysis was based on intention-to-treat (ITT) population (502 evaluable patients) and per-protocol (PP) population (473 evaluable patients). Responses were assessed according to the response criteria of the International Myeloma Working Group (IMWG). Results In the ITT population, patients treated with PAd or VCD were equally distributed for ISS and Durie-Salmon disease stage, LDH, kidney function and the cytogenetic abnormalities translocation t(4;14), deletion 17p13 and gain 1q21. In the PAd group, the median age of the patients was higher (59.4 vs. 58.7, p=0.04). 229 of 251 patients (91.2%) in the PAd group and 241 of 251 patients (96.0%) in the VCD group completed induction treatment. Observed response rates (PAd vs. VCD) were 4.4% vs 8.4% for complete response, 34.3% vs. 37.0% for ≥ very good partial response and 72.1% vs. 78.1% for ≥ partial response. Non-inferiority of VCD compared to PAd was shown (two-sided p=0.0026). Similar results were obtained in the PP analysis. The proportion of patients with any adverse event (AEs) was comparable in PAd vs. VCD (61.3% vs. 64.0%, p=0.58), but more serious adverse events (SAEs) were observed during PAd induction (32.7% vs. 24.0%, p=0.037). VCD led to a significantly higher proportion of leukopenia and neutropenia CTCAE grade 3 and 4 (PAd: 11.3% vs. VCD: 35.2%; p<0.001). There was no significant difference in the number of infections (≥ CTCAE grade 2) during PAd induction compared to VCD induction (24.6% vs. 22.4%; p=0.60). Interestingly, compared to the infection rate (≥ CTCAE grade 2) of 49% during PAD (dexamethasone 40 mg days 1-4, 9-12, 17-20) in the HOVON65/GMMG-HD4-trial, a reduction in MM5 during induction was observed. In the PAd arm more deaths were observed compared to the VCD arm (6 vs. 1). Conclusion PAd and VCD are well tolerated with more than 90% of the patients receiving all three planned induction cycles. Non-inferiority of VCD compared to PAd was shown in ITT and PP analysis. In conclusion, VCD was found to be a valid alternative to PAd with comparable efficacy and a favourable toxicity profile. Disclosures: Goldschmidt: Celgene: Consultancy, Honoraria, Research Funding; Chugai: Research Funding; Janssen Cilag: Consultancy, Honoraria, Research Funding. Duerig:Janssen Cilag: Honoraria; Celgene: Honoraria. Schmidt-Wolf:Janssen: Honoraria; Novartis: Honoraria. Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Scheid:Janssen Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Salwender:Janssen Cilag: Honoraria; Celgene: Honoraria.

Authors: Hartmut Goldschmidt, Jan Duerig, Uta Bertsch, Christina Kunz, Thomas Hielscher, Mathias Haenel, Igor Wolfgang Blau, Dirk Hose, Anna Jauch, Baerbel Schurich, Kai Neben, Anja Seckinger, Barbara Huegle-Doerr, Maximilian Merz, Markus Munder, Walter Lindemann, Matthias Zeis, Christian Gerecke, Ingo GH Schmidt-Wolf, Katja Weisel, Christof Scheid, Hans Salwender

Date Published: 15th Nov 2013

Publication Type: Journal

Powered by
 (v.1.16.1)

(LDH: v0.3.2)

About NFDI4Health | Partners and Funding | Credits
Copyright © 2008 - 2023 The University of Manchester and HITS gGmbH