Oral Clofarabine in the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 118-118 ◽  
Author(s):  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
Zeev Estrov ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Research Funding ◽  
Optimal Dose ◽  
Oral Formulation ◽  
Median Number ◽  
Infectious Complications ◽  
Molecular Characteristics ◽  
Number Of Cycles ◽  
Almost All

Abstract Abstract 118 Clofarabine (CLO) is a second generation deoxyadenosine nucleoside analog with activity in patients (pts) with acute myeloid leukemia (AML). Early reports also suggestedactivity of iv CLO in myelodysplastic syndrome (MDS), but the role of CLO in MDS therapy remains largely undefined. Due to the molecular characteristics of CLO it can also be administered as an oral formulation with a bioavailability of around 50%. As an oral agent has obvious advantages over parenteral administrations, we designed a phase 2 study to evaluate the activity and safety of oral CLO in patients with MDS. Pts were eligible if they had MDS and ≥ 5% blasts (including RAEB-t by FAB) or IPSS intermediate-2 and high-risk, and CMML. Hematopoietic growth factor support prior to and during the study was permitted. Thirty-two pts (2 RA, 11 RAEB-1, 11 RAEB-2, 2 RAEB-t, 5 CMML-1, 1 CMML-2) were treated. Twenty-two pts (69%) had intermediate-2 or high-risk disease by IPSS. Median age was 70 yrs (range 53–86). Overall, ≥ 27 pts (84%) were older than 60 yrs. Thirteen pts (41%) had a history of a prior malignancy and 20 pts (66%) failed prior hypomethylator therapy (6 pts azacitidine, 12 pts decitabine, 2 pts both). Cytogenetics were intermediate and poor in 9 (28%) and 10 (31%) pts, respectively. The starting dose of CLO was 40 mg/m2 orally daily × 5 days every 4–6 weeks (6 pts), which was decreased due to toxicities to 30 mg/m2 orally daily × 5 days (19 pts), and eventually 20 mg/m2 orally daily × 5 days (7 pts). Twenty-eight pts (88%) received treatment in an outpatient facility and almost all pts (94%) received anti-infectious prophylaxis. Responses of 31 evaluable pts are summarized in the Table: Among 20 pts who failed prior hypomethylator therapy responses were CR in 2 (10%), HI in 2 (10%), and CB in 2 (10%). The median number of cycles to response was 1 (range 1–3). Of 10 pts who received further consolidation cycles, the median number was 1 (range 1–8+). No pts died within 6 wks of induction. Acute renal failure occurred in 4 pts (1 pt 40 mg/m2, 3 pts 30 mg/m2) in the context of myelosuppresssion-associated infectious complications; 4 pts died. Common adverse events were nausea/vomiting, rashes, reversible transaminase elevations and hyperbilirubinemia, and fatigue and were mainly ≤ grade 2. The most frequent ≥ grade 3 toxicity were reversible elevations of transaminases. Myelosuppression was ubiquitous, but prolonged myelosuppression (> 42 days) was rare in responding pts. Infectious episodes occurred in 16 pts and were more frequent in pts receiving CLO at 40 or 30 mg/m2. Oral CLO has an ORR of 46% in pts with higher-risk MDS. Responses are lower in pts failing prior hypomethylator therapy. The optimal dose and schedule to balance activity and toxicity remain to be defined. Disclosures: Faderl: Genzyme: Consultancy, Research Funding. Off Label Use: Clofarabine in MDS. Kantarjian:Genzyme: Consultancy, Research Funding.

scholarly journals Double Immune Checkpoint Inhibitor Blockade with Nivolumab and Ipilimumab with or without Azacitidine in Patients with Myelodysplastic Syndrome (MDS)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1831-1831 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Guillermo Montalban-Bravo ◽  
Koji Sasaki ◽  
Naval G. Daver ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Immune Checkpoint Inhibitor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Checkpoint Inhibitor ◽  
Median Number ◽  
Front Line ◽  
Genetics Research ◽  
Number Of Cycles

Abstract Introduction: Myeloid cells express PD1 and CTLA-4. Expression of these molecules is enhanced by azacitidine (AZA). Treatment of patients (pts) with nivolumab (Nivo) and anti-PD1 antibody or ipilimumab (Ipi) and anti-CTLA-4 antibody results in the upregulation of CTLA-4 in patients treated with Nivo and reversely of PD1 in patients treated with Ipi, potentially as a mechanism of evasion. In view of the activity of Nivo and Ipi in MDS (Garcia-Manero, ASH 2016), we hypothesized that dual combination of Nivo + Ipi with AZA could have significant activity in high risk MDS. Methods: To study this, we designed a basket exploratory phase 2 trial of ICPI in MDS. Patients with MDS age 18 or older with adequate renal and hepatic function without history of autoimmune disorders were eligible. Patients were divided into front-line and HMA-failure cohorts. Front-line patients were treated with AZA 75mg/m2 iv daily days 1-5 of a 28 day cycle with Nivo 3 mg/kg iv on days 6 and 20 + Ipi 3 mg/kg iv on day 6. Patients with HMA failure where treated with Nivo 3 mg/kg iv on days 1 and 15 + Ipi 3 mg/kg iv on day 1 of a 28 day cycle. The study design allowed for AZA add-back after 6 cycles of therapy if there was no response or progression. The maximum size per cohort was 20 pts. The primary endpoint was to determine the safety of Nivo or Ipi as single agents or in combination with AZA. Secondary objectives included overall response rate (ORR) and assessment of biological activity. Responses were evaluated following the revised 2006 IWG criteria. The study included stopping rules for response and toxicity. Results: The median follow up was 4.7 months [range 0-10 months]. From January 2017 to April 2018, 14 patients were treated, 6 pts on front-line cohort and 8 on HMA failure. The median age was 69 years [range 52-80]. A total of 4 (29%) pts had Int-1 risk, 6 (43%) had Int-2 and 4 (29%) had High risk by IPSS. Next generation sequencing on whole bone marrow extracted DNA was performed using a 28 gene panel in 5 pts and an 81-gene panel in 9 pts. Cytogenetic abnormalities and identified mutations are shown in Table 1. Median number of marrow blasts was 10 [range 1-16]. Median Hgb was 9.5g/dL [range 7.3-10.9 g/dL], median WBC was 1.5x109/L [range 0.9-4.7] and platelets was 29x109/L [range 8-117]. A total of 13 pts are evaluable for response at the time of analysis. A total of 3 (38%) pts in the HMA failure cohort received AZA after 6 cycles of therapy. The median number of cycles was 4 [range 1-10] with a median number of cycles to response of 3 [range 1-4]. The overall response rate was 50% (3/6) in the frontline cohort, all of them complete responses, and 29% (2/7) in the HMA failure cohort, including 1 complete response and 1 hematological improvement. Adverse events are shown in Table 2. Treatment with Ipi or NIvo had to be held due to rash in 2 pts, due to elevation of creatinine in 2 pts. Early mortality was observed in 1 patient and this was due to pneumonia complicated with respiratory failure and renal failure. The median overall survival is NR in the frontline cohort and is 8.4 months in the HMA failure cohort (Figure 1). Conclusion: Preliminary results suggest double immune checkpoint inhibitor blockade with Ipi and Nivo in combination with AZA in the frontline setting, or in pts with HMA failure is associated with a tolerable safety profile and clinical activity. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Daver:Incyte: Research Funding; Novartis: Consultancy; Alexion: Consultancy; ARIAD: Research Funding; Daiichi-Sankyo: Research Funding; Otsuka: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; Sunesis: Research Funding; Karyopharm: Consultancy; BMS: Research Funding; Incyte: Consultancy; Pfizer: Consultancy; Sunesis: Consultancy; Karyopharm: Research Funding; Kiromic: Research Funding; ImmunoGen: Consultancy. DiNardo:Abbvie: Honoraria; Celgene: Honoraria; Agios: Consultancy; Karyopharm: Honoraria; Medimmune: Honoraria; Bayer: Honoraria. Ravandi:Xencor: Research Funding; Xencor: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Jazz: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Abbvie: Research Funding; Orsenix: Honoraria; Jazz: Honoraria; Macrogenix: Honoraria, Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Bristol-Myers Squibb: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding. Bose:Incyte Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; CTI BioPharma: Research Funding; Celgene Corporation: Honoraria, Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; Blueprint Medicines Corporation: Research Funding. Pemmaraju:plexxikon: Research Funding; daiichi sankyo: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; cellectis: Research Funding; abbvie: Research Funding; SagerStrong Foundation: Research Funding; Affymetrix: Research Funding. Cortes:novartis: Research Funding. Kadia:Jazz: Consultancy, Research Funding; BMS: Research Funding; Abbvie: Consultancy; Novartis: Consultancy; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; BMS: Research Funding; Celgene: Research Funding; Takeda: Consultancy; Celgene: Research Funding; Takeda: Consultancy; Abbvie: Consultancy; Jazz: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Konopleva:Stemline Therapeutics: Research Funding.

scholarly journals Final Report of a Phase II Study of Guadecitabine (SGI-110) in Patients (pts) with Previously Untreated Myelodysplastic Syndrome (MDS)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 232-232 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Koji Sasaki ◽  
Guillermo Montalban-Bravo ◽  
Kristy R. Bodden ◽  
Prithviraj Bose ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Research Funding ◽  
Median Number ◽  
Response To Therapy ◽  
Stopping Rules ◽  
Final Report ◽  
Genetics Research ◽  
Number Of Cycles

Abstract Introduction: The hypomethylating agents (HMA) are the standard of care for a majority of patients with higher-risk MDS. SGI-110 is a second generation HMA that molecularly is a dinucleotide derivative of decitabine and therefore a more potent inhibitor of DNA methyltransferase activity. SGI-110 is currently being studied in front-line AML and second-line MDS multicenter studies. Here we present results of a single arm phase II trial of SGI-110 for patients with previously untreated MDS. Methods: Patients, age 18 or older, with adequate renal and hepatic functions, with int-2 or high risk MDS by IPSS or more than 10% blasts in bone marrow were eligible. One prior cycle of azacitidine or decitabine was allowed. No prior other therapies were allowed. SGI-110 was administered at a dose of 60 mg/m2 SC daily x 5 days every 4 weeks. The study was designed with stopping rules for response, toxicity, and mortality (first 3 months). A maximum of 100 patients could be treated. Results: From 11/14/2014 to 7/31/2018, 94 patients have been treated. Median age was 69 years (22.7-91.9), 72 patients (77%) had INT-2, 13 patients (14%) high risk. Median % of marrow blasts was 10 (range, 0-20). Median white blood cell count and platelet count were 2.5 (×106/L), and 52 (×106/L) respectively. Twenty two patients (23%) were diploid, 36 (38%) complex, and 33 (35%) others. Mutation distribution was as follows: TP53, 29 (31%); ASXL1, 26 (28%); TET2, 20 (21%); RUNX1, 19 (20%); RAS, 12 (13%); DNMT3A, 10 (11%); EZH2, 9 (10%); SRSF2, 6 (7%); PHF6, 4 (4%); BCOR, 3 (3%); CEBPA, 3 (3%); SF3B1, 3 (3%); IDH2, 3 (3%); BRAF, 2 (2%); CBL 2 (2%); MPL, 2 (2%); NPM1, 2 (2%); U2AF1, 2 (2%); WT1, 2 (2%); CREBBP, 1 (1%); ETV6, 1 (1%); FLT3-ITD, 1 (1%); GATA2, 1 (1%); IDH1, 1 (1%); SETBP1, 1 (1%); ZRSR2, 1 (1%). The median number of cycles received was 5 (range 1 - 32). Ninety four (100 %) patients are evaluable for toxicity. Early mortality was 0%. Common toxicities were fatigue (61%), infection (46%), nausea (27%), pain (19%), and constipation (16%), mucositis (16%), dyspnea (15%), local injection toxicity (15%), and diarrhea (12%). Eighty seven (93%) patients were evaluable for response. The median number of cycles to response was 3 (range 1 - 11). Overall response rate was 53 (61%); CR 19 (22%), CRp 3 (3%), HI 31 (36%), SD 5 (6%), NR 27 (31%), and died 2 (2%). With a median follow-up of 15 months, the median OS was 15 months and the median EFS was 14 months (Figure 1). By UVA, higher ACE-27 score showed tendency of lower rates of response (p=0.063; hazard ratio [HR], 1.383; 95% confidence interval [CI], 0.982-1946). However, MVA did not show any prognostic factors for response. By MVA characteristics associated with survival were: complex karyotype (p=0.036; HR, 2.345; 95% CI, 1.055-5.210), and response to therapy (p=0.003; HR, 0.272; 95% CI, 0.114-0.648). In conclusion: SGI-110 is well tolerated in previously untreated MDS. ORR appears to be better than expected compared to azacitidine or decitabine. Longer follow-up and randomized trials will be needed to understand effect on survival. Figure. Figure. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Bose:Incyte Corporation: Honoraria, Research Funding; CTI BioPharma: Research Funding; Celgene Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Blueprint Medicines Corporation: Research Funding; Pfizer, Inc.: Research Funding. Daver:Pfizer: Consultancy; Karyopharm: Research Funding; Novartis: Consultancy; Daiichi-Sankyo: Research Funding; Karyopharm: Consultancy; ARIAD: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Incyte: Consultancy; BMS: Research Funding; Otsuka: Consultancy; Alexion: Consultancy; Sunesis: Consultancy; Pfizer: Research Funding; Sunesis: Research Funding; ImmunoGen: Consultancy; Kiromic: Research Funding. Ravandi:Bristol-Myers Squibb: Research Funding; Sunesis: Honoraria; Orsenix: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria; Xencor: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Orsenix: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Jazz: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. DiNardo:Celgene: Honoraria; Agios: Consultancy; Karyopharm: Honoraria; Abbvie: Honoraria; Bayer: Honoraria; Medimmune: Honoraria. Pemmaraju:SagerStrong Foundation: Research Funding; Affymetrix: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; abbvie: Research Funding; cellectis: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding. Kadia:Novartis: Consultancy; Amgen: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Celgene: Research Funding; BMS: Research Funding; Celgene: Research Funding; Novartis: Consultancy; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Takeda: Consultancy.

Bortezomib + Low Dose Cytarabine in Int-2 and High Risk MDS. Interim Results of a Phase I/II Trial by the GFM.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1453-1453 ◽  
Author(s):  
Shanti Natarajan ◽  
Pierre Fenaux ◽  
Norbert Vey ◽  
A. Guerci ◽  
I. Coulibaly ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Low Dose ◽  
Specific Inhibitor ◽  
Median Number ◽  
Infectious Complications ◽  
High Risk Population ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background: We (Blood.2006;107:1156) and others showed that marrow cells from high-risk MDS patients exhibit constitutive NF-kB activation. Bortezomib (BOR) is a specific inhibitor of NF-kB with limited efficacy when used alone in AML but which is potentiated by its association with chemotherapy especially Cytarabine (AraC) (Cancer Chem Pharm.2006;58:13). Methods: The GFM performed a phase I–II study of BOR in association with low dose AraC (LDAraC) in MDS patients (pts) with intermediate-2 or high IPSS (including RAEB-T). Pts received BOR 1.5 mg/m2 on d 1,4,8,11 and AraC 10mg/m2 d1-14, q 28 days for 4 cycles. In the absence of DLT AraC was increased to 20mg/m2 after cycle 1. Dose reductions were made to BOR (1.3 and 1.0 mg/m2) for NCI-CTCAE >Grade 2 non and >Grade 3 hematologic toxicity. Response was evaluated after 2 and 4 cycles (IWG 2006 criteria). Responding pts could receive up to 4 additional cycles. Results: 44 pts were included between June 2006 and July 2007 (total 49 planned). 37 pts included >8 weeks before date of first interim analysis (1 Jul 2007), were evaluable. Median age 72 yrs (range 54–88) and M:F ratio 25:12. Diagnosis: 2 RA, 3 RAEB-1, 23 RAEB-2, 7 RAEB-T and 2 MDS with myelofibrosis. Prior treatment: 4 LDAraC, 2 intensive chemotherapy, 3 Azacytidine. IPSS: 18 int-2; 19 high. Karyotype was good, intermediate, poor and not done in 14, 4, 18 and 1 pt, respectively (resp). 25 pts had either poor karyotype or were pretreated. Plts were <100 G/L in 30 pts and ANC <1.5 G/L in 30 pts. Median number of cycles received 2.4 (range 1–8). Five responding pts received 2–4 additional cycles. There were 9 AraC dose escalations and 22 BOR reductions. Death with no evidence of progression (< 8 weeks) occurred in 2 pts (sepsis). Nine of the 37 pts (24%), had responses including 3 CR, 2 PR, 1 marrow CR (mCR) with HI and 3 HI. Of the remaining 26 pts 3 were stable after 4 cycles and 23 had progressed. Responses were seen after 3 or more cycles in 8 pts. 3 of 18 pts (17%) with poor karyotype achieved responses (1CR, 1mCR and 1HI) vs 2 of 4 pts with intermediate karyotype (2CR) and 4 of 14 pts (29%) with favourable karyotype (2PR and 2HI). All 9 responses were seen in the 28 previously untreated pts (32%) vs no responses in the 9 pretreated pts. Duration of CR was 9+, 8+ and 8+ mos, PR was 9+ and 6+ mos, mCR was 5+ mos, and HI was 10+,11+ and 12+ mos resp. 27 patients were alive. The 10 deaths were due to 8 progressions and 2 infectious complications. Hospitalization was required in 22 pts during treatment. Non fatal SAEs were mainly due to infections (14), bleeding (7) and skin eruptions (2). Neurotoxicity was seen in 4 pts (1 Gr 3 and 3 Gr 2). Conclusion: In this high risk population BOR + LDAraC gave a 24% response rate (32% in previously untreated pts). Responses were seen including in pts with unfavourable karyotype who generally fail LDAraC alone. Neurotoxicity was only seen in 4 patients. However, there was significantly more myelosupression than with LDAraC alone. An update will be given.

scholarly journals Impact of Induction Treatment on Stem Cell Collection: A COVID Related Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4848-4848
Author(s):  
Brad Rybinski ◽  
Ashraf Z. Badros ◽  
Aaron P. Rapoport ◽  
Mehmet Hakan Kocoglu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Number Of Cycles ◽  
Time Required ◽  
Stem Cell Collection

Abstract Introduction: Standard induction therapy for multiple myeloma consists of 3-6 cycles of bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide and dexamethasone (KRd). Receiving greater than 6 cycles of a lenalidomide containing regimen is thought to negatively impact the ability to collect sufficient CD34+ stem cells for autologous stem cell transplant (Kumar, Dispenzieri et al. 2007, Bhutani, Zonder et al. 2013). Due to the COVID-19 pandemic, at least 20 patients at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) had transplant postponed, potentially resulting in prolonged exposure to lenalidomide containing induction regimens. Here, in the context of modern stem cell mobilization methods, we describe a retrospective study that suggests prolonged induction does not inhibit adequate stem cell collection for transplant. Methods: By chart review, we identified 56 patients with multiple myeloma who received induction with VRd or KRd and underwent apheresis or stem cell transplant at UMGCC between 10/1/19 and 10/1/20. Patients were excluded if they received more than 2 cycles of a different induction regimen, had a past medical history of an inborn hematological disorder, or participated in a clinical trial of novel stem cell mobilization therapy. We defined 1 cycle of VRd or KRd as 1 cycle of "lenalidomide containing regimen". In accordance with routine clinical practice, we defined standard induction as having received 3-6 cycles of lenalidomide containing regimen and prolonged induction as having received 7 or more cycles. Results: 29 patients received standard induction (Standard induction cohort) and 27 received prolonged induction (Prolonged induction cohort) with lenalidomide containing regimens. The median number of cycles received by the Standard cohort was 6 (range 4-6), and the median number of cycles received by the Prolonged cohort was 8 (range 7-13). The frequency of KRd use was similar between patients who received standard induction and prolonged induction (27.58% vs. 25.93%, respectively). Standard induction and Prolonged induction cohorts were similar with respect to clinical characteristics (Fig 1), as well as the mobilization regimen used for stem cell collection (p = 0.6829). 55/56 patients collected sufficient stem cells for 1 transplant (≥ 4 x 10 6 CD34 cells/kg), and 40/56 patients collected sufficient cells for 2 transplants (≥ 8 x 10 6 CD34 cells/kg). There was no significant difference in the total CD34+ stem cells collected at completion of apheresis between standard and prolonged induction (10.41 and 10.45 x 10 6 CD34 cells/kg, respectively, p = 0.968, Fig 2). Furthermore, there was no significant correlation between the number of cycles of lenalidomide containing regimen a patient received and total CD34+ cells collected (R 2 = 0.0073, p = 0.5324). Although prolonged induction did not affect final stem yield, prolonged induction could increase the apheresis time required for adequate collection or result in more frequent need for plerixafor rescue. There was no significant difference in the total number of stem cells collected after day 1 of apheresis between patients who received standard or prolonged induction (8.72 vs. 7.96 x 10 6 cells/kg, respectively, p = 0.557). However, patients who received prolonged induction were more likely to require 2 days of apheresis (44% vs. 25%, p = 0.1625) and there was a trend toward significance in which patients who received prolonged induction underwent apheresis longer than patients who received standard induction (468 vs 382 minutes, respectively, p = 0.0928, Fig 3). In addition, longer apheresis time was associated with more cycles of lenalidomide containing regimen, which neared statistical significance (R 2 = 0.0624, p = 0.0658, Fig 4). There was no significant difference between standard and prolonged induction with respect to the frequency of plerixafor rescue. Conclusions: Prolonged induction with lenalidomide containing regimens does not impair adequate stem cell collection for autologous transplant. Prolonged induction may increase the apheresis time required to collect sufficient stem cells for transplant, but ultimately clinicians should be re-assured that extending induction when necessary is not likely to increase the risk of collection failure. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

Results of an Exploratory Study of Oral (po) and Intravenous (iv) Clofarabine in Patients with Myelodysplastic Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1455-1455 ◽  
Author(s):  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
Varsha Gandhi ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
High Risk ◽  
Optimal Dose ◽  
Risk Groups ◽  
Median Number ◽  
High Dose ◽  
Two Phase ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
Febrile Episodes ◽  
Elevated Transaminases

Abstract Clofarabine (CLO) is an adenosine nucleoside analog with activity in adult acute myeloid leukemia (AML). Its activity in MDS is less well defined. To evaluate the activity and safety of CLO in MDS we designed two phase II studies with iv CLO and po CLO, respectively. Pts were eligible if they had MDS with ≥ 5% blasts, fell into IPSS intermediate-2 and high-risk groups, or had CMML. No prior intensive chemotherapy or high-dose cytarabine was allowed. Hematopoietic growth factor support was permitted. In the iv study pts were adaptively randomized to receive CLO 15 or 30 mg/m2 iv daily x 5 every 4–6 weeks. The second study used a starting dose of CLO 40 mg/m2 orally daily x 5 every 4–6 weeks (assuming oral bioavailability about 50%), which was then decreased to 30 mg/m2 orally daily x 5. Thirty pts (18 RAEB, 6 RAEB-T, 6 CMML) have been treated. Assignment by IPSS for RAEB and RAEB-T pts: 10 high-risk, 10 intermediate-2, and 4 intermediate-1. Fifteen pts received iv CLO and 15 po CLO. Median age was 68 yrs (range 57–86). Median number of prior therapies was 1 (0–4). Twenty (67%) pts received prior decitabine or azacitidine. Karyotype was abnormal in 24 (80%) pts, including 10 pts with −5/−7 abnormalities. Responses were determined according to International Working Group criteria (IWG). Twenty-seven pts were evaluable for response (2 pts too early, one refused further treatment on day 4 of first course). Eleven (41%) pts responded [7 (26%) CR, 2 (7%) HI, 2 (7%) clinical benefit (CB)] (see table). Response (%) Route Dose (mg/m2) N CR HI CB po 40 6 - - 1 (17) 30 6 1(17) 2 (33) 1 (17) iv 30 6 2 (33) - - 15 9 4 (44) - - Response by IPSS: 67% intermediate-1, 44% intermediate-2, 40% high. Twenty-seven pts are evaluable for toxicities. Grade ≥ 3 toxicities occurred in 8 of 13 pts on iv CLO (rash, hyperbilirubinemia, elevated transaminases, elevations of creatinine, acute renal failure) and 4 of 14 pts with po CLO (rash, hyperbilirubinemia, elevated transaminases). Myelosuppression resulting in febrile episodes and hospitalizations with both iv and po CLO was ubiquitous, but prolonged myelosuppression (> 42 days) was rare. In summary, CLO has activity in pts with higher-risk MDS. The optimal dose and schedule for po and iv CLO have not been defined yet. Lower doses of CLO are associated with responses. Correlative PK studies may help to provide further support for optimal dose and route of administration of CLO in pts with MDS.

A Randomized Study of Low Dose Oral Clofarabine 10 Mg Versus 20 Mg (flat dose) Daily × 5 for Patients with Higher-Risk Myelodysplastic Syndrome (MDS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3851-3851
Author(s):  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
Farhad Ravandi ◽  
Jorge E. Cortes ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Randomized Study ◽  
Patient Characteristics ◽  
Median Number ◽  
Infectious Complications ◽  
Advisory Committees ◽  
Platelet Recovery ◽  
Flat Dose ◽  
Secondary Mds

Abstract Abstract 3851 Clofarabine (CLO) is a nucleoside analog with activity in myeloid malignancies. We have previously reported an overall response rate (ORR) of 43% (CR rate 25%) in patients (pts) with higher-risk MDS treated with oral CLO at doses between 20 mg/m2 and 40 mg/m2 daily × 5 (S Faderl et al. J Clin Oncol 2010, 28: 2755). However, myelosuppression and infectious complications were frequent. We therefore developed a trial based on a Bayesian randomization design of CLO 10 mg vs 20 mg (flat dose) orally daily × 5 days with the objective to maintain reasonable efficacy and minimize toxicities. Cycles were repeated every 4 to 8 weeks for up to a total of 12. Pts were eligible if they had MDS with ≥ 5% blasts (including RAEB-t by FAB) or IPSS intermediate-2 and high-risk, and CMML. Hematopoietic growth factor support prior to and during the study was permitted. Thirty-two pts (19 RAEB [59%], 7 RAEB-t [22%], 2 MDS/MPN [6%], 4 CMML [13%]) were randomized. Patient characteristics were similar between the groups and are summarized in Table 1. Table 1: Patient Characteristics Characteristic 10 mg 20 mg N 16 16 Median age, yrs (range) 67.5 (43–87) 72.5 (54–84) Median WBC, ×109/L (range) 4 (1.2–121.3) 4.8 (0.4–47) Median blood blasts, % (range) 0.5 (0–25) 3.5 (0–32) Median marrow blasts, % (range) 12 (4–28) 12 (2–24) Secondary MDS, N (%) 9 (56) 4 (25) Median N prior therapies (range) 1 (0–3) 1 (0–4) Prior hypomethylator therapy, N 14 (88%) 13 (81%) Cytogenetics 5 (31) 6 (38) Diploid, N (%) 4 (25) 4 (25) -5/5q- and/or -7/7q- 4 (25) 2 (13) IM/not done Seven pts (22%) responded: 3 CR and 4 CR without platelet recovery (CRp). Four pts (25%) in the 10 mg group and 3 pts (19%) in the 20 mg group responded (differences not significant). Median remission duration was 6.5 months for all pts (6.5 months [10 mg]; 4.4 months [20 mg], p=.942). The median number of cycles was 2 in each treatment group with a range of 1–4 (10 mg) and 1–12 treatment cycles (20 mg), respectively. One pt in each group died. Median survival for the whole group was 8.5 months (8.2 months [10 mg]; 8.5 months [20 mg], p=.9). Clofarabine at both 10 mg and 20 mg orally daily × 5 has a comparable CR/CRp rate as do higher doses. Myelosuppression does still occur but prolonged myelosuppression has been rare. Even lower doses including at different schedules may still warrant further study. Disclosures: Faderl: Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Clofarabine in MDS. O'Brien:Avila: Research Funding; Bayer: Consultancy; Bristol-Myers Squibb: Research Funding; Gilead Sciences: Consultancy, Research Funding; Celgene: Consultancy; Cephalon: Consultancy; CII Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Genentech BioOncology: Research Funding; Genzyme: Consultancy; GlaxoSmithKline: Consultancy; MorphoSys: Consultancy; Novartis: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Seattle Genetics, Inc.: Consultancy; Sigma Tau Pharmaceuticals: Consultancy; Talon: Research Funding; The Medal Group: Speakers Bureau. Kantarjian:Genzyme: Research Funding.

5-Azacitidine Therapy in Patients with Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia: a Single Institution Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4963-4963
Author(s):  
Alessandra Freyrie ◽  
Gianluigi Reda ◽  
Daniele Vincenti ◽  
Mariarita Sciumé ◽  
Francesca Binda ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Median Number ◽  
Observation Time ◽  
Chronic Myelomonocytic Leukemia ◽  
Female Ratio ◽  
Number Of Cycles ◽  
Male To Female ◽  
Myelomonocytic Leukemia

Abstract Abstract 4963 Overall survival (OS) is significantly improved by 5-azacitidine in intermediate-2 (int-2) and high risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) with 10–29% marrow blasts, and acute myeloid leukemia (AML) with 20–30% marrow blasts, compared with conventional treatments, and currently appears as the standard of care, at least in patients who are not candidates to allogeneic stem cell transplantation (alloSCT). We retrospectively evaluated the efficacy and tolerability of 5-azacitidine in 25 patients treated at our institution from 2009 to 2012, outside of clinical trial. Our series was composed by 17 cases of MDS with IPSS risk int-2 or high, 6 AML with marrow blasts between 20% and 30% and 2 CMML. Patients were treated with 5-azacitidine at a dosage of 75 mg/m2/d subcutaneously for 7 days every 28 days (schedule 5 day on, 2 day off and 2 day on). Median age of our cohort was 72 years (range 37–81 y), male to female ratio was 0. 6 and the median number of cycles received was 7 (range 1–26). According to the MDS-specific comorbidity index 9 pts (53%) were classified as low-risk, 7 pts (41%) as intermediate risk and 1 pt (6%) as high risk. Seventeen (68%) patients (13 MDS, 3 AML, 1 CMML) who had received at least 4 cycles of therapy were evaluable. Median age of these 17 patients was 71 years (range 37–81 y), male to female ratio was 0. 8 and median number of cycles administered was 8 (range 4–26). The overall response rate (ORR) was 59% (10/17 patients). According to International Working Group (IWG) 2006 criteria, five patients (29%) reached complete remission (CR) after a median of 5 cycles of therapy (range 4–6), two patients (12%) obtained hematologic improvement with bone marrow complete remission (marrow CR) after 6 and 11 cycles of therapy respectively, three patients (18%) showed hematologic improvement (HI) after 5 cycles (range 4–6), while stable disease (SD) and progressive disease (PD) were observed in 4 (23%) and in 3 patients (18%) respectively after 5 cycles (range 4–7). Median duration of response was 12 months (range 6–26 mo); median overall survival from the beginning of 5-azacitidine, for all patients treated, was 14. 4 months (range 7–33 mo). We did not observe any differences in response rate according to age, bone marrow fibrosis, cytogenetics and transfusion requirements. In the responder group (10 patients) we did not observe grade 3 or 4 non-hematologic toxicity after a median observation time of 10 months (range 5–33 mo). Among non-responding patients, four (57%) recurred to hospitalization due to infectious or hemorrhagic complications (median observation time 15 months, range 7–33). 5-azacitidine confirmed to be an active therapy for patients with int-2 and high risk MDS and AML with low marrow blast counts not candidate to high intensity treatment for age and or comorbidities, showing high response rate and good tolerability. The low rate of serious adverse events and need of hospitalization improved patient's quality of life and reduced the utilization of medical resources. Disclosures: No relevant conflicts of interest to declare.

Patterns of Infection in Patients with Myeloid Malignancies Receiving 5-Azacytidine: identification of Candidates for Antifungal Prophylaxis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4955-4955
Author(s):  
Cristina Calderón ◽  
Jose F Falantes ◽  
Francisco Márquez-Malaver ◽  
Jose González ◽  
Maria Luz Martino ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Fungal Infection ◽  
Myeloid Leukemia ◽  
Hospital Admissions ◽  
Conflicts Of Interest ◽  
Infectious Complications ◽  
Febrile Episodes ◽  
Acute Myeloid

Abstract Abstract 4955 Introduction Infectious complications are among the most recurrent causes of mortality in patients (pts) with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) undergoing intensive chemotherapy (IC). These pts routinely receive anti-infective prophylaxis (AIP) with flourquinolones and antifungals. 5-azacytidine has recently been incorporated to treatment options for AML and MDS. However, the evidence of the effectiveness of AIP in patients treated with 5 azacytidine (AZA) is limited [1–3]. Objectives To analyze the incidence of episodes of infectious fever (IF), type of microbiological isolation and clinical relevance of infectious complications in AML and MDS pts treated with AZA who did not received prophylaxis. Identification a subgroup of pts who may benefit from AIP in this setting. Material/methods We retrospectively analyzed 48 pts with AML and MDS who received AZA from 2008, with a total of 365 cycles administered. Median age was 68 years (29–83y). Distribution: LMA (n=17) and MDS (n=31). One third of these pts had an absolute neutrophil count (ANC)<0. 5×10e9/L at time of starting AZA. Another 33% of pts had received prior IC, being all refractory to previous treatment. Baseline characteristics in table 1. Results Forty-eight febrile episodes were recorded (13% of IF/cycles of AZA). There was no difference in IF in pts with ANC<0. 5×109/L vs ANC>0. 5×10e9/L (p=0. 53). A total of 17 pts suffered at least one episode of IF (35% of the pts). Hospital admission was required in 14 of these 17 pts with a median time of hospitalization of 14 days (4–80). Mortality attributed to infectious complications ocurred only in 3/48 pts (6%). Twelve microbiological isolations were documented, the most common being: Gram negative bacilli (E Coli=4) and aspergillus reported as probable (n=4) and shown in table 1. Upon comparing pts who received prior IC (n=16; 33%) vs AZA as first line treatment, a higher risk for IF per cycle was observed in first group (18% vs 11. 5%; p=0. 06). Double of these pts developed fever (56% vs 25%; p=0. 03), required more hospital admissions (44% vs 22%; p=0. 21) and had longer duration of hospital stay (22 vs 14 days; p=0. 71). Finally, the group of patients that underwent previous IC, had higher rate of fungal infection by aspergillus and candida (5/9 isolations; 55% vs 0/5; 0%. P <0. 001), although no difference was observed in terms of mortality attributed to infection (6% each group) because of the reduced number of pts who died of this complication overall (3/48). Conclusions To our knowledge, this is the first study to evaluate the frequency and impact of IF in pts treated with AZA not receiving routinely AIP. Overall, the incidence of IF is lower than the reported in similar series. These results allow to identify pts that previously were treated with IC as those at highest risk of fungal infection. Thus, prophylaxis should be considered in this group. Prospective studies are needed to assess the requierement of prophylaxis during treatment with 5 azacytidine. Jain N et al. Benefit of Anti-infectious Prophylaxis in Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome receiving Frontline “Targeted Therapy”. Blood (ASH) 2007, 110:Abstract 2858 Je-Hwan Lee et al. Decreased incidence of febrile episodes with antibiotic prophylaxis in the treatment of decitabine for myelodysplastic syndrome. Leuk Res 35 (2011):499–503 Merkel D et al. Predictive Parameters for Infections During Azacitidine Therapy in High Risk MDS Patients. Blood (ASH) 2011, 118:Abstract 3811 Disclosures: No relevant conflicts of interest to declare.

Ibrutinib In Combination With Rituximab (iR) Is Well Tolerated and Induces a High Rate Of Durable Remissions In Patients With High-Risk Chronic Lymphocytic Leukemia (CLL): New, Updated Results Of a Phase II Trial In 40 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 675-675 ◽  
Author(s):  
Jan A. Burger ◽  
Michael J. Keating ◽  
William G. Wierda ◽  
Julia Hoellenriegel ◽  
Ghayathri Jeyakumar ◽  
...  
Keyword(s):  
High Risk ◽  
Subdural Hematoma ◽  
Research Funding ◽  
Tp53 Mutation ◽  
Single Agent ◽  
Infectious Complications ◽  
Lymphocytic Leukemia ◽  
High Rate ◽  
Grade 3

Abstract The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is a promising new targeted therapy for patients with mature B cell malignancies, especially CLL and mantle cell lymphoma (MCL). Single agent ibrutinib induces an overall response rate (ORR) of 71% in relapsed CLL, based on the Phase 1/2 experience. To accelerate and improve responses to ibrutinib in high-risk CLL, ibrutinib was combined with rituximab; we update this Phase 2 single-center clinical trial with a median follow-up of 14 months. Methods Patients were treated with ibrutinib 420 mg PO daily continuously throughout the study Rituximab (375 mg/m2) was administered weekly for the first four weeks (cycle 1), then monthly until cycle 6.at which point patients continued on ibrutinib monotherapy. Study inclusion required high-risk disease (del17p or TP53 mutation [treated or untreated]), PFS < 36 months after frontline chemo-immunotherapy, or relapsed CLL with del11q. Results Characteristics of the 40 patients enrolled included median age of 65 (range 35–82) with a median of 2 prior therapies. There were14 female and 26 male patients. 20 patients had del17p or TP53 mutation (4 without prior therapy), and 13 patients had del11q. 32 patients had unmutated IGHV, only one patient mutated IGHV, the remaining patients had inconclusive IGHV results. The median β2 microglobulin was 4.2 mg/L (2.2 – 12.3), At a median follow up of 14 months, 32 of 40 patients continue on therapy (16 out of 20 with del17p or TP53 mutation) without disease progression. 39 patients were evaluable for response assessment per 2008 IWCLL guidelines; 34 (87%) achieved partial remission (PR), and three (8%) complete remission (CR), accounting for an ORR of 95%. One CR was negative for MRD by flow cytometry, The ORR in the 20 patients with del17p or TP53 mutation was 90% (16 PR, 2 CR). Among the 8 patients that came off study, 3 patient died from unrelated infectious complications (2 cases of sepsis, 1 case of pneumonia), and 1 died from unrelated respiratory and cardiovascular failure. Two patients came off study because of possibly ibrutinib-related toxicity (one subdural hematoma, one grade 3 mucositis), one patient had progressive disease, and one proceeded to stem cell transplantation. Treatment generally was well tolerated, with infectious complications (6 cases of pneumonia and 3 cases of upper respiratory infections) being the most common complication. There were two Grade 3, possibly related AEs: mucositis (n=1), and peripheral neuropathy (n=1). Milder toxicities included Grade 1-2 bruising (n=7), Grade 1 subdural hematoma (n=1), fatigue (n=2), bone pain, myalgias, and arthralgia (n=5), or diarrhea (n=1). Questionnaires revealed significantly improved overall health and quality of life (QOL) after 6 months, based on the EORTC-QOL-v.3 questionnaire, which coincided with a significant weight gain at 3 and 6 months. Conclusion Ibrutinib in combination with rituximab is a safe, well tolerated regimen for high-risk CLL patients, which induces high rates of durable responses. Responses were associated with significant improvements in QOL. Compared to ibrutinib monotherapy, the redistribution lymphocytosis resolves more rapidly and completely (see Figure), and consequently the ORR is higher. Whether the addition of rituximab to ibrutinib therapy translates into longer progression-free and overall survival will be addressed in an upcoming larger, randomized trial of ibrutinib versus iR in relapsed/refractory CLL. Disclosures: Burger: Pharmacyclics: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Off Label Use: Ibrutinib (PCI-32765) for treatment of high-risk CLL patients. O'Brien:Pharmacyclics: Research Funding.

A Phase II Add-on Study of Vorinostat (VOR) in Higher Risk Myelodysplastic Syndrome with Failure of Hypomethylating Agents (HMA): The GFM Azavor Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2900-2900
Author(s):  
Thomas Prebet ◽  
Jacques Delaunay ◽  
Eric Wattel ◽  
Thorsten Braun ◽  
Pascale Cony-Makhoul ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Response Rate ◽  
Standard Of Care ◽  
Median Number ◽  
Current Standard ◽  
Stage Design ◽  
Early Evaluation ◽  
Positive Results

Abstract Background: Azacitidine (AZA) is the current standard of care for patients treated for higher risk MDS, but 40-50% patients do not respond and most responders eventually relapse. Median survival after AZA failure is only 5 months and no standard of care is defined for this population. Preclinical studies and positive results of phase I-II trials support a synergistic effect of the histone deacetylase (HDAC) vorinostat (VOR) and AZA in terms of response, although no survival advantage of the combination has as yet been demonstrated. We hypothesized that adding VOR to AZA in patients with primary or secondary AZA resistance could rescue response and prolong survival. Methods: inclusion criteria inGFM AZAVOR study (NCT 01748240) were: 1/IPSS int 2 or high risk MDS at the time of initiation of AZA 2/treatment with at least 6 cycles of AZA and either failure to achieve any response or loss of response (per IWG2006 criteria) 3/a maximum of 3 months between AZA failure and inclusion with no other treatment in between. Patients received VOR 300mg bid from day 3 to day 9 of each cycle. AZA was given at standard 75mg/m2/d day 1 to 7 or at the maximum previously tolerated dose in case of dose reduction. Patients were evaluated after 6 cycles and responding patients treated until progression. The trial used a two-stage design, and accrual was to be stopped if less than 3 responses were seen in the first 14 evaluable patients. Results 21 patients were included between march 2013 and September 2014. Nineteen patients were treated (1 patient died and 1 progressed before treatment). Median age was 72 years. All pts had higher risk MDS and had received a median of 6 cycles of AZA before entering the trial. The median number of AZA+ VOR cycles administered was 3 (range: 1-12). No unexpected SAEs were seen, and the most common AEs were infection, thrombocytopenia, GI toxicities, and fatigue. After 6 cycles of treatment, only 2 patients (11%) achieved response (1 erythroid hematological improvement, 1 partial remission), , which, per protocol, triggered the stop of accrual. At last follow-up, 18 patients were off study and one patient was still on treatment. Nine patients stopped treatment because of progression (42%), 4 stopped treatment for lack of response (21%), 2 stopped treatment because of intolerance (11%), 1 patient stopped at his request (5%), and 1 patient died of complications of cytopenias while on treatment (5%). Median overall survival was 13 months. Conclusion This is the first report of an add-on study in high risk MDS, a strategy that may be useful for the early evaluation of drugs for which synergy with AZA is expected. Our results show that the proposed regimen of AZA +VOR can be used safely. However, the observed response rate was not above the "background" response rate expected from AZA alone continuation in a comparable patient population, indicating that the addition of VOR cannot reverse resistance to AZA. Disclosures Prebet: CELGENE: Research Funding. Off Label Use: lenalidomide. Wattel:Janssen: Consultancy, Honoraria, Research Funding; PIERRE FABRE MEDICAMENTS: Research Funding; CELGENE: Research Funding, Speakers Bureau; NOVARTIS: Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding. Cony-Makhoul:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Fenaux:Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding. Vey:Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria.

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