VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantion (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 450-450 ◽  
Author(s):  
Jean Luc Harousseau ◽  
Claire Mathiot ◽  
Michel Attal ◽  
Gerald Marit ◽  
Denis Caillot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Standard Of Care ◽  
Response Assessment ◽  
Primary Objective ◽  
Induction Treatment ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Phase Ii Studies ◽  
The Impact

Abstract Introduction. ASCT is considered the standard of care for younger patients (pts) with MM. The benefit of ASCT is at least partly related to an increase in Complete Remission (CR) plus Very Good Partial Remission (VGPR) rate. One way to increase the CR rate is to improve the induction treatment prior to ASCT. Several phase II studies with Vel in combination as induction treatment yielded promising CR rates. We have previously tested the Vel/D combination with Vel 1.3mg/m2 d1,4,8,11 with 40mg/d d1–4, d 9–12 for 4 consecutive 21d cycles (D only on d1–4 during cycles 3–4) (Harousseau et al Haematologica 2006). Methods. In July 2005, the IFM initiated a randomized Phase II trial comparing Vel/D with VAD as induction treatment prior to ASCT in pts with newly diagnosed MM up to the age of 65.This IFM 2005/01 was closed for accrual in January 2007 after having recruited 482 patients. The primary objective was the CR (negative immunofixation) plus n-CR (negative electrophoresis) after 4 cycles. The second question was to evaluate the impact of a consolidation with 2 cycles of DCEP (D, Cyclophosphamide, Etoposide, Platinum). At diagnosis pts were randomized between 4 arms (A1:4 cycles of VAD, A2: 4 cycles of VAD + 2 cycles of DCEP, A3:4 cycles of Vel/D, A4:4 cycles of Vel/D + 2 cycles of DCEP). Randomization was stratified according to β2-microglobulin and del 13 by FISH analysis. Stem cell collection was performed between cycle 3 and 4 after G-CSF priming (10μg/kg x 6d). ASCT was prepared by melphalan 200mg/m2. Results. As of Aug 2007, data from the first consecutively enrolled 222 pts have been analyzed (A1:54,A2:56,B1:55,B2:57). In the VAD arms (A1+A2),88% of pts received the planned 4 courses versus 94% in the Vel/D arms (B1+B2). In arm A2,87.5% of pts received the 2 cycles of DCEP versus 82% in arm B2. ASCT was performed in 94% of evaluable pts in arms A1+A2 and in 92% in arms B1+B2. The number of SAE was the same in the VAD and the Vel/D arms. The incidence of grade 3–4 averse events was also comparable. However the proportion of pts with neurological symptoms (all grades) during induction treatment was higher with Vel/D (36% versus 11%). Response assessment is available for 208 pts (100 VAD, 108 Vel/D). The results are shown in the table (intent-to-treat analysis). Consolidation with DCEP did not increase the CR rate (16% pre-ASCT both in arms A1+B1 and in arms A2+B2). Conclusion. This analysis not only confirms that the post-induction CR rate is increased by Vel/D compared to VAD (Harousseau ASH 2006) but also shows that this benefit translates in higher CR+VGPR rates after ASCT. Longer follow-up is needed to demonstrate that this better tumor reduction induces longer PFS and OS. Currently 1-year PFS and OS rates are respectively 90% and 95% with VAD, 93% and 97% with Vel/D. Updated results will be presented at the meeting.

Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma

2009 ◽  
Vol 27 (30) ◽  
pp. 5015-5022 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Tara Kendall ◽  
Ammar Al-Zoubi ◽  
Yasser Khaled ◽  
Shin Mineishi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Initial Treatment ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Pegylated Liposomal Doxorubicin ◽  
Combination Regimen ◽  
Newly Diagnosed ◽  
Painful Neuropathy ◽  
The Impact

PurposeThis single-center, open-label, phase II trial evaluated the bortezomib, pegylated liposomal doxorubicin (PLD), and dexamethasone combination regimen (VDD) as initial treatment for patients with newly diagnosed multiple myeloma (MM).Patients and MethodsEnrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m2intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m2IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/near-complete response (CR/nCR) rate after six cycles. Secondary end points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The impact of VDD on stem-cell mobilization and collection also was evaluated.ResultsAfter six cycles, the ORR was 85.0% (CR/nCR, 37.5%; very good partial response [VGPR] or better, 57.5%). Patients who underwent stem-cell transplantation (SCT) after VDD (n = 30) experienced increased rates of VGPR or better (53.3% to 76.6% after SCT). Overall, 1-year PFS and OS rates were 92.5% and 97.5%, respectively. Those who achieved VGPR or better after treatment with VDD showed a significantly greater 1-year PFS versus those who achieved less than VGPR (100% v 82%, respectively; P = .03). Similar results were observed in patients who underwent SCT. Grades 3 or 4 hematologic toxicities occurred in ≤ 10% of patients; grade 2 painful neuropathy occurred in 7.5%; and grade 3 palmar-plantar erythrodysesthesia occurred in 2.5%.ConclusionVDD is highly effective for initial treatment of MM followed by SCT in appropriate patients, and it has a reasonable safety profile. Achievement of VGPR or better with this initial therapy predicted longer PFS, regardless of the consolidation therapy given.

VELCADE/Dexamethasone (Vel/Dex) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM): An Interim Analysis of the IFM 2005-01 Randomized Multicenter Phase III Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 56-56 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Gerald Marit ◽  
Denis Caillot ◽  
Philippe Casassus ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Interim Analysis ◽  
Primary Objective ◽  
Phase Iii ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Significance Level ◽  
Β2 Microglobulin

Abstract ASCT is considered the standard of care for patients up to 65 years of age with MM. The optimal induction treatment prior to ASCT is still unknown. VAD is a commonly used regimen but is associated with a number of toxicities, administrative inconvenience, and a complete remission (CR) rate of typically less than 10%. Recently the combination thalidomide/Dex was reported to induce a higher overall response rate than Dex alone in newly diagnosed patients, but with significantly more toxicities, especially deep vein thrombosis, and a 4% CR rate (Rajkumar et al, J Clin Oncol 2006;24:431–6). In a phase II trial we have evaluated the combination of Vel 1.3mg/m2 D1, 4, 8, 11 with Dex 40mg/D D1-4, D9-12, for 4 consecutive 21-D cycles (Dex only on D1-4 during cycles 3–4). This combination was well tolerated and yielded a 21% CR/nCR rate with successful stem cell harvest and engraftment (Harousseau et al, Haematologica 2006). In 2005, the IFM initiated a multicenter randomized phase III trial comparing Vel/Dex with VAD as induction treatment of patients with newly diagnosed MM up to the age of 65. The primary objective of the study is the CR (negative immunofixation) plus nCR (CR but positive immunofixation) rate after 4 cycles. A secondary objective is to evaluate the role of consolidation with 2 courses of DCEP (Dex, cyclophosphamide, etoposide, cisplatin). Patients were randomized at diagnosis among 4 arms (A1: 4 cycles of VAD; A2: 4 cycles of VAD + 2 cycles of DCEP; B1: 4 cycles of Vel/Dex; B2: 4 cycles of Vel/Dex + 2 cycles of DCEP); stratification was by cytogenetics and β2 microglobulin. Stem cell collection was performed between cycle 3 and cycle 4 after priming with G-CSF (10μg/kg/D × 6 D). At the end of induction (± DCEP consolidation) treatment, patients received melphalan 200mg/m2 plus ASCT. Enrollment of 480 patients is planned, to detect a 10% higher CR/nCR rate with Vel/Dex (20% vs 10%) with 80% power (two-sided test, significance level 0.05). An interim analysis is planned when 222 patients have been evaluated for response at the end of induction. As of July 2006, 304 patients have been enrolled. Randomization of the 222 patients to be considered for interim analysis was completed on May 19th. Baseline characteristics include: median age 55y; 140M, 82F; β2 microglobulin >3mg/L in 54%; del13 by FISH in 45%. The occurrence of serious adverse events (SAEs) was similar between the VAD and Vel/Dex arms (31% with VAD, 33% with Vel/Dex). The most frequent SAEs were pneumopathy (5.3% VAD, 4.0% Vel/Dex), thrombosis (2.7% VAD, 3.3% Vel/Dex), and peripheral neuropathy (1.3% VAD, 3.3% Vel/Dex). We intend to present results from the interim analysis.

scholarly journals Bortezomib Maintenance Therapy after Induction with R-CHOP, ARA-C and Autologous Stem Cell Transplantation in Newly Diagnosed MCL Patients, Results of a Multicenter Phase II HOVON Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 339-339 ◽  
Author(s):  
Jeanette K Doorduijn ◽  
Monique C. Minnema ◽  
Marie Jose Kersten ◽  
Pieternella J Lugtenburg ◽  
Martin R. Schipperus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Research Funding ◽  
Progressive Disease ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Introduction. The standard first-line treatment of young and fit mantle cell lymphoma (MCL) patients consists of a rituximab containing induction of CHOP and high dose ARA-C, followed by high dose consolidation and autologous stem cell transplant (ASCT). Thus far, almost all patients relapse after ASCT. Bortezomib is a proteasome inhibitor with activity in MCL. We investigated in a randomized phase II study whether there was any indication that maintenance therapy with bortezomib after ASCT could improve the outcome of treatment, measured as event free survival (EFS). Methods. Patients 18-65 years with newly diagnosed MCL were treated with 3 cycles of R-CHOP and 2 cycles of ARA-C (2 x 2 g/m2 iv d1-4) and rituximab (375 mg/m2, iv d11). Patients in PR or CR continued with ASCT after BEAM conditioning. Patients with a PR or CR after ASCT, with a neutrophil count > 0.5 x 109/l and platelets > 80 x 109/l were randomized between bortezomib and no further treatment. Bortezomib 1.3 mg/m2 iv was given once every two weeks, for 2 years, starting between 6 - 12 weeks after transplantation. Results . Between October 2007 and February 2012, 140 patients aged 34-66 years (median 57) were registered. Five patients were not eligible. The MIPI score was low, intermediate, high or unknown in 57%, 32%, 10% and 1% respectively. All eligible patients started induction treatment with R-CHOP. Two patients did not receive the first ARA-C cycle, because of progressive disease and physician decision. Hundred-fifteen patients (85%) received the BEAM and ASCT. Reasons to stop protocol treatment before ASCT were: progressive disease (PD) (n=6), inadequate stem cell harvest (n=3), excessive toxicity (n=3), other reasons (n=8). The response after ASCT was CR/CRu in 99 patients (86%), PR in 15 (13%), unknown in 1 (1%). Only 62 patients (45%), aged 34-65 years (median 56) were randomized between bortezomib maintenance and no further treatment. Two patients were randomized, but not eligible. Reasons for no randomization were: not eligible (n=30), patient refusal (n=14), excessive toxicity (n=2, and other reasons (n=7). In each treatment arm 30 patients were included. The patient characteristics were well balanced, except the MIPI score. In the no maintenance arm 21 patients (70%) had a low MIPI, compared to 15 patients (50%) in the bortezomib arm, and 6 (20%) versus 11 (37%) patients had an intermediate MIPI score. In both arms 3 patients (10%) had a high MIPI. Fifteen patients (50%) in the maintenance group continued bortezomib for 2 years. Reasons to stop earlier were excessive toxicity (n=6), PD/relapse (n=4), patients refusal (n=3) and other (n=2). The main adverse events during maintenance therapy were neurologic (CTC grade 2: 14%, grade 3: 4%), and infectious (grade 2: 11%, grade 3: 7%). Three patients developed a secondary malignancy: a basal cell carcinoma in the no maintenance group, a melanoma and a prostate carcinoma in the bortezomib group. With a median follow-up of the patients still alive of 50.9 months EFS at 4 years for all patients is 61%, and the overall survival (OS) 78%. The median follow-up of the randomized patients still alive is 42.9 months. The EFS at 4 years is 72% without maintenance versus 71% in the patients randomized for bortezomib maintenance. The OS at 4 years also shows no significant difference between the groups, 90% versus 93% respectively. Conclusion. There is no indication that bortezomib iv maintenance in a frequency of once every 2 weeks does improve the EFS of newly diagnosed MCL patients after intensive induction treatment with R-CHOP, double ARA-C and BEAM followed by ASCT. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Doorduijn: Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Off Label Use: bortezomib maintenance in MCL. Minnema:Celgene: Consultancy; Jansen Cilag: Consultancy; Amgen: Consultancy. Kersten:janssen: Honoraria, Research Funding; takeda millennium: Research Funding; roche: Honoraria, Research Funding. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Schipperus:Novartis: Consultancy. Zijlstra:Celgene: Consultancy; Roche: Consultancy.

scholarly journals Thalidomide Does Not Compromise Mobilization with Cytokine Alone in Multiple Myeloma after Triplet Induction Regimen

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5691-5691
Author(s):  
Matevz Skerget ◽  
Matjaz Sever ◽  
Barbara Skopec
Keyword(s):  
Multiple Myeloma ◽  
Body Weight ◽  
Stem Cell ◽  
Statistical Difference ◽  
Standard Of Care ◽  
Optimal Dose ◽  
Stem Cell Mobilization ◽  
Induction Treatment ◽  
Cell Mobilization ◽  
The Impact

Abstract Background Multiple myeloma (MM) is a hematologic disease characterized by accumulation of malignant plasma cells in the bone marrow. Triplet induction regimens incorporating bortezomib, thalidomid and dexamethasone (VTD) or bortezomib, cyclophosphamide and dexamethasone (VCD) are current standard of care because of improved response and prolonged progression free survival (PFS) and overall survival (OS). Autologous hematopoietic stem cell transplantation (aHSCT), performed in first remission or at relapse, is standard of care for younger fit patients. Successful mobilization and collection of peripheral blood stem cells (PBSC) is required before aHSCT. A target dose of 2 x 106 PBSC per kg body weight is considered a minimum for timely hematopoetic reconstitution, although a higher dose, 3 to 5 x 106 PBSC per kg body weight, is thought to be optimal for earlier engraftment. Mobilization with chemotherapy (intermediate doses of cyclophosphamide) and granulocyte-colony stimulating factor (G-CSF) is a standard in most transplant centers and provides higher stem cell yields in fewer apheresis procedures, at the cost of increased toxicity and less predictable onset date of apheresis in comparison to G-CSF alone mobilization. G-CSF alone mobilization fails to achieve the target doses of PBSC in up to 20 % of patients. There is limited information on possible impact of novel agents on ability to successfully mobilize and harvest PBSC. From available data, the impact of thalidomide on stem cell mobilization is small and probably not of clinical significance, but most of it comes from trials incorporating mobilization with chemotherapy and not G-CSF alone mobilization. Due to feasibility and safety reasons our institution uses G-CSF alone mobilization in MM patients. Mobilization with chemotherapy and/or prelixafor is reserved for poor mobilizers. The aim of our study was to retrospectively evaluate the success of GCSF alone mobilization in patients who received either VTD or VCD induction and possible differences between two groups. Patients and methods We retrospectively analyzed data from our national registry from the 1/1/2014 until 12/31/2017. Seventy-two patients with newly diagnosed MM that received induction treatment with VTD or VCD and underwent stem cell mobilization with G-CSF alone were included. VTD treatment consisted of 3 week cycles of bortezomib 1.3 mg/m2 subcutaneous on days 1, 4, 8 and 11, thalidomide 100 mg daily and dexamethasone 40 mg on days 1 - 4 of the first cycle and once per week thereafter. VCD treatment incorporated bortezomib and dexamethasone at the same schedule as for VTD plus cyclophosphamide 500 mg/m2 on day 1, 8 and 15 of each cycle. Following 3 - 4 cycles of induction treatment, stem cells were mobilized using daily subcutaneous injections of G-CSF 10 mg/kg body weight (doses were rounded up according to available 300 mcg and 480 mcg vials) for 5 consecutive days. The number of circulating PBSC was determined in peripheral blood on day 5 by flow cytometry and apheresis was initiated at a CD34+ cell count > 20/μL. A dose of 2 × 106 PBSC per kg body weight and 3 × 106 PBSC per kg body weight were considered the minimal and optimal dose for a single transplant. Results Twenty-eight and 44 patients received induction treatment with VCD or VTD respectively (Table 1). The mobilization failure rate between the groups was 7 % and 9 % for VCD and VTD. There was no statistical difference in the number of apheresis procedures, collected PBSC and the ability to collect a minimal and optimal dose for 2 aHSCT between the two groups (Table 2). Conclusions Due to higher efficacy, VTD is preferred over VCD with no data available on the impact of these regimens on stem cell mobilization with G-CSF alone. The results of our retrospective study showed that thalidomide in the VTD regimen did not influence the number of collected PBSC or the number of apheresis procedures compared to VCD. The failure rate for both groups was low. There was no statistical difference in collecting the optimal dose for two aHSCT between the groups. In conclusion, induction with VTD can be safely used in centers using G-CSF alone mobilization without compromising the ability for stem cell harvest. Disclosures No relevant conflicts of interest to declare.

Randomized phase II 8-arm factorial study of adjuvant dose-dense (dd) temozolomide (TMZ) with permutations of thalidomide (Thal), isotretinoin (CRA), and/or celecoxib (Cel) for newly diagnosed glioblastoma (GBM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2003-2003
Author(s):  
Mark R. Gilbert ◽  
Kenneth R. Hess ◽  
Lore Lagrone ◽  
Morris D. Groves ◽  
Victor A. Levin ◽  
...  
Keyword(s):  
Factorial Design ◽  
Phase Ii ◽  
Standard Of Care ◽  
Hepatic Function ◽  
Newly Diagnosed ◽  
Cytostatic Agents ◽  
Current Standard ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
The Impact

2003 Background: Concurrent radiation and TMZ followed by 6-12 months of adjuvant TMZ (d 1-5 of a 28d cycle) is the current standard of care for patients with newly diagnosed GBM. The addition of cytostatic or signal transduction agents may enhance efficacy without a significant increase in toxicity. A phase I trial (Neuro-oncology 2009) established the safety of ddTMZ with 2 or 3 of the cytostatic agents. Methods: This randomized phase II study was conducted by the Brain Tumor Trials Collaborative (BTTC) and the MDACC CCOP. The primary objectives: determine if specific cytostatic agents added to ddTMZ alters outcomes (PFS, OS) and compare triplet with doublet therapy. Eligibility criteria: centrally confirmed newly diagnosed GBM, age ≥18, KPS≥60, stable or improved after chemoradiation (pseudoprogression allowed), adequate hematologic, renal and hepatic function. Pts were randomly assigned to 12 treatment cycles (28 d/cycle) in 8 arms: ddTMZ alone (150 mg/m2/day, 7-d on, 7-d off) or TMZ-containing doublet, triplet and quadruplet combinations with Thal, CRA, or Cel. Results: The study enrolled 155 eligible patients from 11/2005 to 9/2010 to the 8 arms of the factorial design. Median age was 53 (18-84) and median KPS, 90 (60-100). Compared with TMZ alone, the TMZ+CRA doublet had worse PFS (10.5, 6.5 mo; p=0.043) and OS (21.2, 11.7 mo; p=0.037). Trends were also seen for worse outcome (PFS, OS) for CRA-containing regimens, improved OS for Cel containing arms and no impact of Thal. A strong trend for OS improvement was seen for triplet compared with doublet regimens (20.1, 17.0 mo; p=0.15), but no difference for PFS. Treatment was well tolerated with expected high rates of grade 3/4 lymphopenia, and overall a modest toxicity rate. Conclusions: The results indicate that the addition of CRA to ddTMZ may be detrimental in patients with newly diagnosed GBM. This study demonstrated the utility of the factorial design in efficiently testing drug combinations, the impact of individual agents in these combinations as well as doublet vs. triplet regimens and supports its utility in testing combinations of targeted agents.

The Prognostic Impact of Complete Remission (CR) Plus Very Good Partial Remission (VGPR) in a Double-Transplantation Program for Newly Diagnosed Multiple Myeloma (MM). Combined Results of the IFM 99 Trials.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3077-3077 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Philippe Moreau ◽  
Frédéric Garban ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Partial Remission ◽  
Response Assessment ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Fish Analysis ◽  
Prognostic Impact ◽  
Logrank Test ◽  
Transplantation Program ◽  
The Impact

Abstract Introduction. In MM, the impact of CR achievement is still a matter of debate. In the IFM 90 and IFM 94 trials the achievement of CR (negative electrophoresis with or without negative immunofixation) plus very good partial remission (90% reduction of the M-component) was significantly associated with longer overall survival (OS) (M. Attal et al: NEJM1996;348:1875–83 and M. Attal et al; NEJM2003; 349: 2495–502). We wanted to check the impact of this simple way of response assessment in a program of double transplantation designed with the objective of increasing the CR rate. Methods. In the risk-adapted IFM 99 trials, therapeutic strategy was based on the assessement of two adverse prognostic factors (β2 microglobulin > 3 mg/L; del (13) by FISH analysis). All patients up to 65 years of age were to receive a double transplantation after an induction treatment with 3–4 courses of VAD. In standard risk MM (0 or 1 adverse prognostic factors), patients received a double autologous stem-cell transplantation (ASCT) (Melphalan 140 mg/m2/Melphalan 200 mg/m2) and were there randomized between no further treatment, pamidronate, or Thalidomide plus pamidronate (IFM 99/02). In high risk MM (2 adverse prognostic factors), patients received a first ASCT (after Melphalan 200 mg/m2) followed by either a reduced-intensity allogeneic SCT if an HLA-identical sibling was available (IFM 99/03) or a second ASCT (after Melphalan 220 mg/m2 ± anti IL-6 antibody) (IFM 99/04). Results. With a median follow-up time of 47 months, the median event-free survival (EFS) was 39 months and the probability of 5-year OS was 62%. Best response to treatment was assessed in 849 patients: CR was achieved in 274 patients (32%) and VGPR in 191 patients (22.5%), while 311 patients (37%) had only a partial remission (PR) and 73 pts (8.5%) had a stable or progressive disease. Median EFS and 5-year OS were respectively 42 months and 77% for patients who achieved CR, 38 months and 63% for patients with VGPR, 30 months and 55% for patients with PR. The outcome was significantly better for the 465 patients with at least 90% reduction of their M-component (CR+VGPR) than for the 384 patients with < PR (median EFS 40 months versus 28 months, p=7.10–6) and 5-year OS 72% versus 52%, p=6.10–6). Response to the induction treatment with VAD was assessed in 700 patients: 112 (16%) had at least a VGPR. As compared to the 588 with less than VGPR there was no difference in EFS or in OS (p=0.23 and p=0.67 respectively, logrank test). Conclusion. In the context of a double transplantation program, CR + VGPR is obtained in 54.5 % of patients. We confirm that the quality of response is significantly correlated to the outcome and that achievement of CR + VGPR which can be assessed by very simple means, has a strong prognostic impact. We were not able to show a benefit of achieving CR+ VGPR after the induction treatment with VAD but 353/465 (76%) achieved this status only after the double transplant program.

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

2020 ◽  
Vol 51 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Matevz Skerget ◽  
Barbara Skopec ◽  
Matjaz Sever
Keyword(s):  
Stem Cell ◽  
Outcome Measures ◽  
Standard Of Care ◽  
National Registry ◽  
Newly Diagnosed ◽  
Treatment Groups ◽  
Cell Counts ◽  
Significant Difference ◽  
The Impact ◽  
Cell Harvest

AbstractTriplet 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.

scholarly journals CTIM-15. PRELIMINARY RESULTS OF A PHASE II STUDY OF NIVOLUMAB WITH HYPOFRACTIONATED RE-RADIATION AND BEVACIZUMAB FOR RECURRENT MGMT METHYLATED GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii36-ii36
Author(s):  
Christian Grommes ◽  
Minesh Mehta ◽  
Alexandra Miller ◽  
Mariza Daras ◽  
Anna Piotrowski ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Disease Recurrence ◽  
Primary Objective ◽  
Significant Finding ◽  
Trial Treatment

Abstract Standard of standard of care for glioblastoma (GBM) remains unsatisfactory with universal disease recurrence and a median survival of &lt; 2 years. Immune checkpoint inhibitors (ICI) have shown limited single-agent activity in GBM thus far. GBMs with methylated MGMT promoter and no baseline corticosteroid dependence may be most likely to derive benefit from ICI. The combination of ICIs with radiation has shown promising activity in other human cancers. Combining nivolumab and re-RT/bevacizumab in GBM may augment ICI activity through immunogenic effects of radiation, may reduce the risk of radiation necrosis by addition of bevacizumab at the time of radiation, and may reduce the need for corticosteroids. In this multicenter phase II study, nivolumab is combined with re-irradiation and optional concurrent bevacizumab followed by nivolumab in patients with first recurrence of IDH-wildtype and MGMT methylated glioblastoma. Primary objective is to improve 1-year overall survival (OS) from 33 (based on EORTC 26101) to 50%. Nine-three patients are required to show a significant finding with an α of 0.05 and 81% power. Thirteen of 93 patient (14%) have been enrolled with a median age of 59 (range 42–71) with a median KPS of 90 (range 70–90). Treatment has been tolerated well without any grade ≥ 4 toxicities and only one grade 3 (amylase elevation). The most common adverse events were pruritus and hypothyroidism in 3/13 (23%). The median progression-free survival (PFS) is 7 months with a 6months PFS of 55.6%. The 12months OS is 66.7%. Patients with recurrent MGMT methylated, IDH-wildtype glioblastoma tolerate trial treatment with acceptable toxicities. Clinical efficacy in the first patients enrolled shows a promising effect. Enrollment is ongoing.

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