INDRÁK, Karel - DOUBEK, Michael - VOGLOVÁ, Jaroslava - KOZA, Vladimír - KOZÁK, Tomá - MAALOUFOVÁ... more INDRÁK, Karel - DOUBEK, Michael - VOGLOVÁ, Jaroslava - KOZA, Vladimír - KOZÁK, Tomá - MAALOUFOVÁ, Jacqueline - KOTOUČEK, Pavol - DEMITROVIČOVÁ, Ludmila - TÓTHOVÁ, Elena - CHUDEJ, Juraj - SZOTKOWSKI, Tomá - MAYER, Jiří - ÁK, Pavel - ...
3862 Poster Board III-798 Acute light chain (LC) induced renal failure (ARF) is a severe complica... more 3862 Poster Board III-798 Acute light chain (LC) induced renal failure (ARF) is a severe complication of progressive MM. Reversal of ARF can only be achieved by fast, substantial and continuous suppression of production of pathogenic LCs. Bortezomib is highly effective and well tolerated in myeloma patients (pts) with renal impairment, because its metabolism is independent of renal function. In this study we evaluated the efficacy of Bortezomib in combination with doxorubicin and dexamethasone (BDD) in restoring renal function and in achieving tumor control in pts with LC-induced renal failure. In total, 72 pts have been enrolled; 2 pts did not fulfil inclusion criteria, 2 pts had been excluded because kidney biopsy revealed renal amyloidosis as main cause of renal failure. Hence, 68 pts constituted the intent to treat population and 58 pts were evaluable per protocol (≥2 cycles of therapy). Age: median 65.8; range 41-79 years. Forty-six (79%) pts presented with de novo MM, and 12 (...
6537 Background: Thalidomide-Dexamethasone (TD) has shown activity in pts with relapsing or refra... more 6537 Background: Thalidomide-Dexamethasone (TD) has shown activity in pts with relapsing or refractory multiple myeloma (MM). In the present trial we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly pts with MM. Methods: 137 of 350 pts planned have been enrolled (median age: 72 yrs, stage I: 6 (4%), stage II: 52 (38%), stage III: 79 (58%). Pts are randomised to either T 200mg/d and D 40mg, d1–4 and 15–18 on odd cycles and d1–4 on even cycles or M 2.5mg/kg d1–4 and P 2mg/kg d1–4, q 4–6 weeks. The dose of T is increased to 400mg/d if feasible. Pts achieving response or stabilisation are randomised to maintenance treatment either with T (maximal dose 200mg/d)-Interferon alpha-2b (3Mega U, TIW) or Interferon alpha-2b (3Mega U/TIW). All pts are scheduled for monthly zolendronate (4mg). Results: 93 pts are evaluable for response. Best response to TD was: CR 6 (13%), NCR 4 (8%), VGPR 5 (10%) PR 8 (17%), MR 7 (15%) yielding an ORR of 63%. 3 pts had SD (6%) and 15 PD or failure (3...
doi:10.1182/blood-2009-01-198093Prepublished online May 21, 2009;2009 114: 1166-1173€€€€Annick Be... more doi:10.1182/blood-2009-01-198093Prepublished online May 21, 2009;2009 114: 1166-1173€€€€Annick Bessems, Peter De Porre, Angela J. Howes and for the FIGHT-AML-301 InvestigatorsRobak, Nuriet K. Khuageva, Anatoly K. Golenkov, Elena Tothova, Lars Mollgard, Youn C. Park, Johan Maertens, Maria-Belen Vidriales, Herve Dombret, Xavier Thomas, Alan K. Burnett, TadeuszDominique Bordessoule, Tamas Masszi, Gert J. Ossenkoppele, Julia A. Alexeeva, Gernot Beutel, Jean-Luc Harousseau, Giovanni Martinelli, Wieslaw W. Jedrzejczak, Joseph M. Brandwein,€
New international staging system applied in 588 patients: Experience of the Czech myeloma group b... more New international staging system applied in 588 patients: Experience of the Czech myeloma group based on analysis of the one multicenter trial (4W) and two single center experiences
Project ALERT (Acute LEukemia clinical RegisTry) was initiated 11 years ago. The database is repr... more Project ALERT (Acute LEukemia clinical RegisTry) was initiated 11 years ago. The database is representative for the Czech population, at least in the category of curatively treated AML patients. Presented cohort consists of 1890 AML patients registered from January 1996 to February 2007.
Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment ... more Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment of multiple myeloma (MM) patients (pts). In this report, we describe the longterm outcome of cohort of 185 pts with newly diagnosed symptomatic MM treated with ASCT. Median follow-up from the start of therapy was 102.8 months (range 67.2–150.4). We have specifically analyzed benefit from the newer drugs used in the relapsed setting. Methods: A total of 185 MM pts underwent ASCT in the clinical trial 4W of Czech Myeloma Group in 18 centres in Czech Republic and Slovak Republic between 1996 and 2001. The conditioning regimen was high dose melphalan (200mg/m2) in all pts. At diagnosis of MM 72.4% (134/185) of pts had stage III according to Durie- Salmon, 18.4% (34/185) stage II and 9.2% (17/185) stage I. Clinical stages according to ISS were the following: stage 1 in 42.5% (74/174) of pts, stage 2 in 36.8% (64/174) and stage 3 in 20.7% (36/174) pts. Types of monoclonal immunoglobulin were a...
5051 While clinical studies and guidelines provide important data regarding the safety and effica... more 5051 While clinical studies and guidelines provide important data regarding the safety and efficacy of new drugs, their application to daily practice can be limited by the inclusion of selected patient populations. Population-based studies can provide additional insight into the complex process of implementing treatment guidelines in daily practice. The objective of the MyDyS registry was to collect and analyze data regarding the diagnosis and management of patients with myelodysplastic syndrome (MDS) in Slovakia. Material and methods: five clinical centers collected data regarding demographics, staging, history and cytopathology from newly diagnosed patients (pts) with MDS from 2009 to 2011. Patients were classified according to the French American British (FAB) and World Health Organization (WHO) systems and the International Prognostic Scoring System (IPSS). The database allowed online pts registration. Results: one hundred thirty pts were registered to MyDyS in the yrs 2009–2011...
Thalidomide-Dexamethasone (TD) is an active regimen both in patients (pts) with relapsing/refract... more Thalidomide-Dexamethasone (TD) is an active regimen both in patients (pts) with relapsing/refractory and in untreated pts with multiple myeloma (MM). Here we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly pts with MM. 274 pts have been enrolled (median age: 72 yrs, stage I: 9 (3%), stage II: 84 (31%), stage III: 179 (65%). Pts were randomized to T 200mg/day and D 40mg, days 1–4 and 15–18 (on odd cycles) and days 1–4 (on even cycles) or M 0.25mg/kg days 1–4 and P2mg/kg days 1–4, q 4–6 weeks. T should be dosed up to 400mg/day, if feasible. Pts achieving response or SD were randomized to maintenance therapy either with T (≤200mg/day)-Interferon-a2b (IFN, 3Mega U, TIW) or IFN (3Mega U/TIW). Zoledronic acid (4mg) was administered monthly to all pts during the entire treatment period. Response is defined according Blade’s criteria, plus nCR defined as IF positive or >90%↓ in PP and VGPR defined as >75% ↓reduction in PP. 231 pts are evaluable per p...
Introduction: With the onset of tyrosine kinase inhibitors (TKI) to treat patients with CML, the ... more Introduction: With the onset of tyrosine kinase inhibitors (TKI) to treat patients with CML, the number of patients and overall survival increased and quality of life significantly improved. The basic principle of therapy was also changed, according to the clinical practice now it is aimed at early induction of deep molecular response. Objective: To characterize the CML patient population and TKI treatment results in clinical practice in CML patients in Slovak republic (SR). Methods: The observational study…
1239 Background. Imatinib (IM), a selective BCR-ABL tyrosine kinase inhibitor (TKI), is a treatme... more 1239 Background. Imatinib (IM), a selective BCR-ABL tyrosine kinase inhibitor (TKI), is a treatment of choice for newly diagnosed chronic myeloid leukemia (CML) patients (pts) in chronic phase (CP) as it was shown in the IRIS trial. The treatment strategy and response evaluation is based on NCCN or ELN guidelines. Only limited “real life” data of IM impact on pts outcome as well as ELN (European LeukemiaNet) recommendations applicability in daily practice has been published. In the Czech as well as in the Slovak Republic (15 million inhabitants), the treatment of CML patients is centralized in overall 13 centers, capable carrying on both the treatment and laboratory monitoring. There are two CML prospective projects CAMELIA and INFINITY focused on CML pts analysis. Aims. To analyze the treatment response and long-term outcome in consecutive, unselected patients with CP-CML treated with IM and to evaluate the prognostic role of ELN 2006 and 2009 response evaluation. To analyze molecu...
4439 Background: Most results on the treatment of chronic myeloid leukemia (CML) with imatinib we... more 4439 Background: Most results on the treatment of chronic myeloid leukemia (CML) with imatinib were obtained from clinical trials that may differ from the routine practice. We report the results of treatment of consecutive CML patients at ten major centers during 2000–2010. Patients and methods: Data reporting was retrospective in 2000– 2004 and prospective from 2005 on. A total of 295 patients (137 women and 158 men; median age 49 [range, 15–81]) with Ph+ CML were registered. The median follow-up was 45.4 months (0–113,5). Results: Most patients were treated with first- (169; 57.28%) or second-line (84; 28.5%) imatinib, part of patients underwent allogeneic hematopoietic stem cell transplantation (AHSCT) (28; 9,5%), but 4,7 % were treated with other modalities (14 patients; median age 66 [range, 32–83]). The probability of overall survival (OS) according to Kaplan and Meier at five years was 88.9%, 77.5% and 68.7% for chronic phase patients treated with first-, second-line imatinib...
2891 Poster Board II-867 Thalidomide maintenance therapy after completion of induction therapy pl... more 2891 Poster Board II-867 Thalidomide maintenance therapy after completion of induction therapy plus ASCT and also after conventional therapy yielded conflicting results with some trials showing improvement in overall survival and others not. This study evaluates the efficacy of Thalidomide plus Interferon a2b (Thal-IFN) in comparison to interferon a2b (IFN) as maintenance therapy in elderly pts with multiple myeloma. For induction therapy, 289 pts had been randomized to either Thalidomide-Dexamethasone or to Melphalan-Prednisolone; results of this part of the study had been reported previously (BLOOD, 113, 3435-3442, 2009). 137 pts who had completed 9 cycles of induction therapy and had achieved stable disease or better were eligible for maintenance treatment, and 128 (median age 72 years, range 54 - 86 years) had finally been randomized to either Thal (starting dose: 200mg/day) in combination with IFN-a2b (Schering-Plough, 3 Mega U, TIW) or IFN a2b (IFN) at the same dose/schedule o...
Introduction Perifosine (PERI) is an oral, synthetic alkylphospholipid that inhibits or modifies ... more Introduction Perifosine (PERI) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK, with potent anti-myeloma activity pre-clinically. In a phase I/II study, an overall response rate (ORR; defined as PR or better) of 41% was demonstrated with PERI in combination with bortezomib (BTZ) ± dexamethasone (DEX) in 73 evaluable multiple myeloma (MM) patients (pts) with relapsed and refractory disease, including an ORR of 65% in BTZ-relapsed pts and 32% in BTZ-refractory pts. Based on these results, a placebo-controlled Phase III study evaluated the benefit of adding PERI at 50 mg daily to BTZ+DEX in MM pts who had previously relapsed after a BTZ-based regimen and received between 1 and 4 prior lines of therapy. Methods This was a double-blind, placebo-controlled randomized study. Eligible pts had measurable disease (baseline serum M-protein > 0.5 g/dL and/or > 200 mg/24-hr urinary M-protein excretion), had relapsed more than 60 days after BTZ-based therapies received as either single agent (at least two 21-day cycles) or in combination with other agents. Pts were randomized 1:1 to PERI (50 mg PO QD) + BTZ (1.3 mg/m2on Day 1, 4, 8, 11) + DEX (20 mg on Day 1, 2, 4, 5, 8, 9, 11, 12) or placebo + BTZ + DEX. Randomization was stratified according to prior lines of therapy (1 vs. > 1) and disease status after last therapy (refractory or relapsed with treatment-free interval < vs. > 6 months). Serum/urine protein electrophoresis (SPEP/UPEP) were performed by a central laboratory at the start of each 21-day treatment cycle to assess disease status until confirmed disease progression. Response or progression by non-SPEP/UPEP or by local laboratory SPEP/UPEP were adjudicated by an independent reviewer blinded to treatment arms and all responses were assessed using modified EBMT and Uniform Criteria. Survival status was assessed every 3 months. Progression-free survival (PFS) after randomization was the primary endpoint. Overall survival (OS) and response rate were secondary endpoints. Toxicity was assessed using version CTCAE 3.0 across both arms and for all grades of adverse events encountered, with attribution assessed locally and centrally as part of standard monitoring practice for safety. Results Between March 2010 and March 2013 (3 years), 135 pts were randomized (PERI=69, placebo=66) at 48 study sites. At that point, 80 events (progression or death) had been observed and the first planned interim analysis was performed by an independent data safety and monitoring committee. Baseline demographics were reasonably balanced between groups: age < 65 years (PERI=61%, placebo=42%), male (PERI=60%, placebo= 56%), ECOG PS 0 (PERI=57%, placebo=54%), and pts with > 1 line of prior therapy, relapse and treatment-free ≥ 6 months (PERI=39%, placebo=38%). PFS was PERI=22.7 weeks, placebo=39 weeks (HR 1.269 [0.817, 1.969], p=0.287). In contrast, median OS was PERI=141.9 weeks, placebo=83.3 weeks which was actuarially in favor of PERI but did not achieve significance (HR 0.734 [0.380, 1.419], p=0.356). Similarly, clinical benefit rate (CBR=SD or >) was as follows: PERI=46.4%, placebo=43.9%, with best ORR (CR+PR) PERI=20.3%, placebo=27.3%, which was historically low for both arms in this setting, and suggests relatively resistant disease in the pts selected and available for analysis. Encouragingly, no safety concerns were observed between PERI and placebo. Limited study logistics and enrollment challenges resulted in very slow accrual, in particular early on in the conduct of the trial, and as a result substantially constrained the sample size. The study was subsequently discontinued following the recommendation of the monitoring committee. Conclusion Although OS was greater by first interim analysis, this Phase III study showed no benefit in PFS or ORR when adding PERI to BTZ and DEX in pts with highly resistant, relapsed and refractory MM previously treated with BTZ at the time of this pre-planned early evaluation of outcome. Tolerability appeared favorable at the dose of PERI selected. Slow accrual and small sample size restrict the ability to definitively interpret these results further. However, other signal tranduction pathway inhibitors of Akt and NFkB continue in development for pts with advanced MM, and are demonstrating promising early results, thus supporting additional study for this potentially important class of anti-MM agents. Disclosures: Richardson: Aeterna Zentaris: Advisory Committee Other; Celgene: Advisory Committee, Advisory Committee Other; Millennium: Advisory Committee, Advisory Committee Other; J & J: Advisory Committee, Advisory Committee Other. Hari:Celgene: Consultancy; Onyx: Consultancy. Martinez-Lopez:Celgene: Honoraria, Research Funding. Ghobrial:Onyx: Advisoryboard Other; BMS: Advisory board, Advisory board Other, Research Funding; Noxxon: Research Funding; Sanofi: Research Funding. Sportelli:Keryx…
INDRÁK, Karel - DOUBEK, Michael - VOGLOVÁ, Jaroslava - KOZA, Vladimír - KOZÁK, Tomá - MAALOUFOVÁ... more INDRÁK, Karel - DOUBEK, Michael - VOGLOVÁ, Jaroslava - KOZA, Vladimír - KOZÁK, Tomá - MAALOUFOVÁ, Jacqueline - KOTOUČEK, Pavol - DEMITROVIČOVÁ, Ludmila - TÓTHOVÁ, Elena - CHUDEJ, Juraj - SZOTKOWSKI, Tomá - MAYER, Jiří - ÁK, Pavel - ...
3862 Poster Board III-798 Acute light chain (LC) induced renal failure (ARF) is a severe complica... more 3862 Poster Board III-798 Acute light chain (LC) induced renal failure (ARF) is a severe complication of progressive MM. Reversal of ARF can only be achieved by fast, substantial and continuous suppression of production of pathogenic LCs. Bortezomib is highly effective and well tolerated in myeloma patients (pts) with renal impairment, because its metabolism is independent of renal function. In this study we evaluated the efficacy of Bortezomib in combination with doxorubicin and dexamethasone (BDD) in restoring renal function and in achieving tumor control in pts with LC-induced renal failure. In total, 72 pts have been enrolled; 2 pts did not fulfil inclusion criteria, 2 pts had been excluded because kidney biopsy revealed renal amyloidosis as main cause of renal failure. Hence, 68 pts constituted the intent to treat population and 58 pts were evaluable per protocol (≥2 cycles of therapy). Age: median 65.8; range 41-79 years. Forty-six (79%) pts presented with de novo MM, and 12 (...
6537 Background: Thalidomide-Dexamethasone (TD) has shown activity in pts with relapsing or refra... more 6537 Background: Thalidomide-Dexamethasone (TD) has shown activity in pts with relapsing or refractory multiple myeloma (MM). In the present trial we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly pts with MM. Methods: 137 of 350 pts planned have been enrolled (median age: 72 yrs, stage I: 6 (4%), stage II: 52 (38%), stage III: 79 (58%). Pts are randomised to either T 200mg/d and D 40mg, d1–4 and 15–18 on odd cycles and d1–4 on even cycles or M 2.5mg/kg d1–4 and P 2mg/kg d1–4, q 4–6 weeks. The dose of T is increased to 400mg/d if feasible. Pts achieving response or stabilisation are randomised to maintenance treatment either with T (maximal dose 200mg/d)-Interferon alpha-2b (3Mega U, TIW) or Interferon alpha-2b (3Mega U/TIW). All pts are scheduled for monthly zolendronate (4mg). Results: 93 pts are evaluable for response. Best response to TD was: CR 6 (13%), NCR 4 (8%), VGPR 5 (10%) PR 8 (17%), MR 7 (15%) yielding an ORR of 63%. 3 pts had SD (6%) and 15 PD or failure (3...
doi:10.1182/blood-2009-01-198093Prepublished online May 21, 2009;2009 114: 1166-1173€€€€Annick Be... more doi:10.1182/blood-2009-01-198093Prepublished online May 21, 2009;2009 114: 1166-1173€€€€Annick Bessems, Peter De Porre, Angela J. Howes and for the FIGHT-AML-301 InvestigatorsRobak, Nuriet K. Khuageva, Anatoly K. Golenkov, Elena Tothova, Lars Mollgard, Youn C. Park, Johan Maertens, Maria-Belen Vidriales, Herve Dombret, Xavier Thomas, Alan K. Burnett, TadeuszDominique Bordessoule, Tamas Masszi, Gert J. Ossenkoppele, Julia A. Alexeeva, Gernot Beutel, Jean-Luc Harousseau, Giovanni Martinelli, Wieslaw W. Jedrzejczak, Joseph M. Brandwein,€
New international staging system applied in 588 patients: Experience of the Czech myeloma group b... more New international staging system applied in 588 patients: Experience of the Czech myeloma group based on analysis of the one multicenter trial (4W) and two single center experiences
Project ALERT (Acute LEukemia clinical RegisTry) was initiated 11 years ago. The database is repr... more Project ALERT (Acute LEukemia clinical RegisTry) was initiated 11 years ago. The database is representative for the Czech population, at least in the category of curatively treated AML patients. Presented cohort consists of 1890 AML patients registered from January 1996 to February 2007.
Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment ... more Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment of multiple myeloma (MM) patients (pts). In this report, we describe the longterm outcome of cohort of 185 pts with newly diagnosed symptomatic MM treated with ASCT. Median follow-up from the start of therapy was 102.8 months (range 67.2–150.4). We have specifically analyzed benefit from the newer drugs used in the relapsed setting. Methods: A total of 185 MM pts underwent ASCT in the clinical trial 4W of Czech Myeloma Group in 18 centres in Czech Republic and Slovak Republic between 1996 and 2001. The conditioning regimen was high dose melphalan (200mg/m2) in all pts. At diagnosis of MM 72.4% (134/185) of pts had stage III according to Durie- Salmon, 18.4% (34/185) stage II and 9.2% (17/185) stage I. Clinical stages according to ISS were the following: stage 1 in 42.5% (74/174) of pts, stage 2 in 36.8% (64/174) and stage 3 in 20.7% (36/174) pts. Types of monoclonal immunoglobulin were a...
5051 While clinical studies and guidelines provide important data regarding the safety and effica... more 5051 While clinical studies and guidelines provide important data regarding the safety and efficacy of new drugs, their application to daily practice can be limited by the inclusion of selected patient populations. Population-based studies can provide additional insight into the complex process of implementing treatment guidelines in daily practice. The objective of the MyDyS registry was to collect and analyze data regarding the diagnosis and management of patients with myelodysplastic syndrome (MDS) in Slovakia. Material and methods: five clinical centers collected data regarding demographics, staging, history and cytopathology from newly diagnosed patients (pts) with MDS from 2009 to 2011. Patients were classified according to the French American British (FAB) and World Health Organization (WHO) systems and the International Prognostic Scoring System (IPSS). The database allowed online pts registration. Results: one hundred thirty pts were registered to MyDyS in the yrs 2009–2011...
Thalidomide-Dexamethasone (TD) is an active regimen both in patients (pts) with relapsing/refract... more Thalidomide-Dexamethasone (TD) is an active regimen both in patients (pts) with relapsing/refractory and in untreated pts with multiple myeloma (MM). Here we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly pts with MM. 274 pts have been enrolled (median age: 72 yrs, stage I: 9 (3%), stage II: 84 (31%), stage III: 179 (65%). Pts were randomized to T 200mg/day and D 40mg, days 1–4 and 15–18 (on odd cycles) and days 1–4 (on even cycles) or M 0.25mg/kg days 1–4 and P2mg/kg days 1–4, q 4–6 weeks. T should be dosed up to 400mg/day, if feasible. Pts achieving response or SD were randomized to maintenance therapy either with T (≤200mg/day)-Interferon-a2b (IFN, 3Mega U, TIW) or IFN (3Mega U/TIW). Zoledronic acid (4mg) was administered monthly to all pts during the entire treatment period. Response is defined according Blade’s criteria, plus nCR defined as IF positive or >90%↓ in PP and VGPR defined as >75% ↓reduction in PP. 231 pts are evaluable per p...
Introduction: With the onset of tyrosine kinase inhibitors (TKI) to treat patients with CML, the ... more Introduction: With the onset of tyrosine kinase inhibitors (TKI) to treat patients with CML, the number of patients and overall survival increased and quality of life significantly improved. The basic principle of therapy was also changed, according to the clinical practice now it is aimed at early induction of deep molecular response. Objective: To characterize the CML patient population and TKI treatment results in clinical practice in CML patients in Slovak republic (SR). Methods: The observational study…
1239 Background. Imatinib (IM), a selective BCR-ABL tyrosine kinase inhibitor (TKI), is a treatme... more 1239 Background. Imatinib (IM), a selective BCR-ABL tyrosine kinase inhibitor (TKI), is a treatment of choice for newly diagnosed chronic myeloid leukemia (CML) patients (pts) in chronic phase (CP) as it was shown in the IRIS trial. The treatment strategy and response evaluation is based on NCCN or ELN guidelines. Only limited “real life” data of IM impact on pts outcome as well as ELN (European LeukemiaNet) recommendations applicability in daily practice has been published. In the Czech as well as in the Slovak Republic (15 million inhabitants), the treatment of CML patients is centralized in overall 13 centers, capable carrying on both the treatment and laboratory monitoring. There are two CML prospective projects CAMELIA and INFINITY focused on CML pts analysis. Aims. To analyze the treatment response and long-term outcome in consecutive, unselected patients with CP-CML treated with IM and to evaluate the prognostic role of ELN 2006 and 2009 response evaluation. To analyze molecu...
4439 Background: Most results on the treatment of chronic myeloid leukemia (CML) with imatinib we... more 4439 Background: Most results on the treatment of chronic myeloid leukemia (CML) with imatinib were obtained from clinical trials that may differ from the routine practice. We report the results of treatment of consecutive CML patients at ten major centers during 2000–2010. Patients and methods: Data reporting was retrospective in 2000– 2004 and prospective from 2005 on. A total of 295 patients (137 women and 158 men; median age 49 [range, 15–81]) with Ph+ CML were registered. The median follow-up was 45.4 months (0–113,5). Results: Most patients were treated with first- (169; 57.28%) or second-line (84; 28.5%) imatinib, part of patients underwent allogeneic hematopoietic stem cell transplantation (AHSCT) (28; 9,5%), but 4,7 % were treated with other modalities (14 patients; median age 66 [range, 32–83]). The probability of overall survival (OS) according to Kaplan and Meier at five years was 88.9%, 77.5% and 68.7% for chronic phase patients treated with first-, second-line imatinib...
2891 Poster Board II-867 Thalidomide maintenance therapy after completion of induction therapy pl... more 2891 Poster Board II-867 Thalidomide maintenance therapy after completion of induction therapy plus ASCT and also after conventional therapy yielded conflicting results with some trials showing improvement in overall survival and others not. This study evaluates the efficacy of Thalidomide plus Interferon a2b (Thal-IFN) in comparison to interferon a2b (IFN) as maintenance therapy in elderly pts with multiple myeloma. For induction therapy, 289 pts had been randomized to either Thalidomide-Dexamethasone or to Melphalan-Prednisolone; results of this part of the study had been reported previously (BLOOD, 113, 3435-3442, 2009). 137 pts who had completed 9 cycles of induction therapy and had achieved stable disease or better were eligible for maintenance treatment, and 128 (median age 72 years, range 54 - 86 years) had finally been randomized to either Thal (starting dose: 200mg/day) in combination with IFN-a2b (Schering-Plough, 3 Mega U, TIW) or IFN a2b (IFN) at the same dose/schedule o...
Introduction Perifosine (PERI) is an oral, synthetic alkylphospholipid that inhibits or modifies ... more Introduction Perifosine (PERI) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK, with potent anti-myeloma activity pre-clinically. In a phase I/II study, an overall response rate (ORR; defined as PR or better) of 41% was demonstrated with PERI in combination with bortezomib (BTZ) ± dexamethasone (DEX) in 73 evaluable multiple myeloma (MM) patients (pts) with relapsed and refractory disease, including an ORR of 65% in BTZ-relapsed pts and 32% in BTZ-refractory pts. Based on these results, a placebo-controlled Phase III study evaluated the benefit of adding PERI at 50 mg daily to BTZ+DEX in MM pts who had previously relapsed after a BTZ-based regimen and received between 1 and 4 prior lines of therapy. Methods This was a double-blind, placebo-controlled randomized study. Eligible pts had measurable disease (baseline serum M-protein > 0.5 g/dL and/or > 200 mg/24-hr urinary M-protein excretion), had relapsed more than 60 days after BTZ-based therapies received as either single agent (at least two 21-day cycles) or in combination with other agents. Pts were randomized 1:1 to PERI (50 mg PO QD) + BTZ (1.3 mg/m2on Day 1, 4, 8, 11) + DEX (20 mg on Day 1, 2, 4, 5, 8, 9, 11, 12) or placebo + BTZ + DEX. Randomization was stratified according to prior lines of therapy (1 vs. > 1) and disease status after last therapy (refractory or relapsed with treatment-free interval < vs. > 6 months). Serum/urine protein electrophoresis (SPEP/UPEP) were performed by a central laboratory at the start of each 21-day treatment cycle to assess disease status until confirmed disease progression. Response or progression by non-SPEP/UPEP or by local laboratory SPEP/UPEP were adjudicated by an independent reviewer blinded to treatment arms and all responses were assessed using modified EBMT and Uniform Criteria. Survival status was assessed every 3 months. Progression-free survival (PFS) after randomization was the primary endpoint. Overall survival (OS) and response rate were secondary endpoints. Toxicity was assessed using version CTCAE 3.0 across both arms and for all grades of adverse events encountered, with attribution assessed locally and centrally as part of standard monitoring practice for safety. Results Between March 2010 and March 2013 (3 years), 135 pts were randomized (PERI=69, placebo=66) at 48 study sites. At that point, 80 events (progression or death) had been observed and the first planned interim analysis was performed by an independent data safety and monitoring committee. Baseline demographics were reasonably balanced between groups: age < 65 years (PERI=61%, placebo=42%), male (PERI=60%, placebo= 56%), ECOG PS 0 (PERI=57%, placebo=54%), and pts with > 1 line of prior therapy, relapse and treatment-free ≥ 6 months (PERI=39%, placebo=38%). PFS was PERI=22.7 weeks, placebo=39 weeks (HR 1.269 [0.817, 1.969], p=0.287). In contrast, median OS was PERI=141.9 weeks, placebo=83.3 weeks which was actuarially in favor of PERI but did not achieve significance (HR 0.734 [0.380, 1.419], p=0.356). Similarly, clinical benefit rate (CBR=SD or >) was as follows: PERI=46.4%, placebo=43.9%, with best ORR (CR+PR) PERI=20.3%, placebo=27.3%, which was historically low for both arms in this setting, and suggests relatively resistant disease in the pts selected and available for analysis. Encouragingly, no safety concerns were observed between PERI and placebo. Limited study logistics and enrollment challenges resulted in very slow accrual, in particular early on in the conduct of the trial, and as a result substantially constrained the sample size. The study was subsequently discontinued following the recommendation of the monitoring committee. Conclusion Although OS was greater by first interim analysis, this Phase III study showed no benefit in PFS or ORR when adding PERI to BTZ and DEX in pts with highly resistant, relapsed and refractory MM previously treated with BTZ at the time of this pre-planned early evaluation of outcome. Tolerability appeared favorable at the dose of PERI selected. Slow accrual and small sample size restrict the ability to definitively interpret these results further. However, other signal tranduction pathway inhibitors of Akt and NFkB continue in development for pts with advanced MM, and are demonstrating promising early results, thus supporting additional study for this potentially important class of anti-MM agents. Disclosures: Richardson: Aeterna Zentaris: Advisory Committee Other; Celgene: Advisory Committee, Advisory Committee Other; Millennium: Advisory Committee, Advisory Committee Other; J & J: Advisory Committee, Advisory Committee Other. Hari:Celgene: Consultancy; Onyx: Consultancy. Martinez-Lopez:Celgene: Honoraria, Research Funding. Ghobrial:Onyx: Advisoryboard Other; BMS: Advisory board, Advisory board Other, Research Funding; Noxxon: Research Funding; Sanofi: Research Funding. Sportelli:Keryx…
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Papers by Elena Tothova