Hematologic Response To Oral Azacitidine (CC-486) In Subjects With WHO-Defined RAEB-1 Or RAEB-2 Myelodysplastic Syndromes (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1554-1554 ◽  
Author(s):  
Guillermo Garcia -Manero ◽  
Michael Savona ◽  
Steven D. Gore ◽  
Christopher R. Cogle ◽  
Paul Conkling ◽  
...  
Keyword(s):  
Phase I ◽  
Lower Risk ◽  
Research Funding ◽  
Performance Status ◽  
Phase Iii ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Overall Response ◽  
Hematologic Response ◽  
Oncology Research

Abstract Background Subcutaneous (SC) azacitidine prolongs overall survival in subjects with higher-risk MDS (Fenaux, JCO, 2009). Previous Phase I and II studies have shown extended oral azacitidine dosing schedules to be safe and effective in subjects with IPSS-defined lower-risk MDS (Garcia-Manero et al, ASH 2010 and ASH 2012). Objective To assess the efficacy and safety of extended oral azacitidine dosing schedules in subjects with WHO-defined RAEB-1 or RAEB-2 MDS. Methods The subset of subjects with WHO-defined RAEB-1 or RAEB-2 MDS from two ongoing Phase I/II studies was included in this ad hoc analysis. Subjects received oral azacitidine 300mg QD or 200mg BID for 14 or 21 days of repeated 28-day cycles. For purposes of this analysis, subject data were analyzed collectively. Hematologic responses were defined by International Working Group (IWG) 2006 criteria. Overall Response was calculated as any response of complete or partial remission (CR or PR), RBC or platelet transfusion independence (TI), and/or any hematologic improvement (HI). Marrow complete remission (mCR) was not included in Overall Response. Serious treatment-emergent adverse events (STEAEs) that occurred in 2 or more subjects are reported. Results Of 23 subjects in all, 20 received 300mg QD oral azacitidine x 14 or 21 days/28-day cycle and 3 received oral azacitidine 200mg BID x 14 days/28-day cycle. Subjects had median age of 71 (range: 36 - 90) years and were predominantly male (61%). Fourteen subjects (61%) had a diagnosis of RAEB-1 and 9 (39%) had RAEB-2, median time from diagnosis was 2.1 (0.1 - 33.2) months, and ECOG performance status scores were 0 (n=4, 17%), 1 (n=15, 65%), or 2 (n=4, 17%). Five subjects had received prior MDS treatments (azacitidine injection; erythropoiesis stimulating agent [ESA]; thalidomide; azacitidine injection and decitabine; G-CSF, anti-thymocyte globulin, methylprednisolone, cyclosporine, and ESA). Median number of oral azacitidine treatment cycles was 3 (1 - 29). Overall Response was achieved by 11/22 subjects (50%) (Table). Four subjects achieved mCR only and are not included in the Overall Response category. RBC TI was achieved by 5/12 subjects (42%) and platelet TI was achieved by 2/5 subjects (40%). Two subjects were able to consolidate remission and proceed to allogeneic stem cell transplant and 1 subject progressed to AML on-study. Oral azacitidine was generally well tolerated. Three subjects discontinued treatment due to an AE. STEAEs were consistent with the known safety profile of SC azacitidine. Of 8 subjects who had an STEAE of febrile neutropenia, pneumonia, and/or septic shock, 3 were severely neutropenic (ANC <0.5 x 109/L) at baseline. Other STEAEs were diarrhea, nausea, and vomiting (n=2 subjects each). Conclusions This analysis in subjects with RAEB-1 and RAEB-2 is the first to assess extended oral azacitidine dosing schedules in higher-risk MDS. One-half of treated subjects achieved a hematologic response to oral azacitidine, which is easy to administer and was generally well-tolerated. Two Phase III studies of extended oral azacitidine dosing (in lower-risk MDS and as maintenance therapy in older patients with AML) are ongoing. Results of these large studies will better elucidate the use of extended oral azacitidine dosing schedules in treating hematologic malignancies. Disclosures: Gore: Celgene Corporation: Consultancy. Cogle:Celgene Corporation: Honoraria, Research Funding. Conkling:US Oncology: Research Funding. Beach:Celgene Corporation: Employment. Hetzer:Celgene Corporation: Employment. Dong:Celgene Corporation: Employment. Skikne:Celgene Corporation: Employment.

AOP2014, a Novel Peg-Proline-Interferon Alpha-2b with Improved Pharmacokinetic Properties, Is Safe and Well Tolerated and Shows Promising Efficacy in Patients with Polycythemia Vera (PV)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 175-175 ◽  
Author(s):  
Heinz Gisslinger ◽  
Robert Kralovics ◽  
Bettina Gisslinger ◽  
Daniel Lechner ◽  
Veronika Buxhofer-Ausch ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Iii ◽  
Molecular Response ◽  
Overall Response ◽  
Long Term Treatment

Abstract Abstract 175 AOP2014 is a next generation long-acting pegylated IFNa-2b, consisting predominantly of only one isoform, as opposed to other commercially available pegylated interferons. AOP2014 has a distinct pharmacokinetic and pharmacodynamic profile which may potentially allow reduced dosing frequencies compared to other pegylated IFNs. This is being expected to result in improved tolerability, better compliance, and, finally, favorable long-term treatment outcomes. AOP2014 is a designated Orphan Drug in EU for treatment of patients with PV. The maximum tolerated dose (MTD), long term safety and efficacy of AOP2014, administered subcutaneously every 14 days, are the main objectives of the study. Patients with confirmed PV diagnosis, age equal or older 18 years, both naïve and cytoreduction pre-treated are eligible. After establishing the MTD, an extended cohort of 25 additional patients was planned to be recruited. European LeukemiaNet criteria were used for response assessment. 34 patients, treated by March 31, 2012 were included into this analysis: 25 in Phase I (dose-finding) and 9 in the Phase II (cohort extension). Median time from diagnosis was 24 months (range 0–180). 12 patients (35%) were HU pre-treated (mean past duration of HU pre-treatment 39 months, mean daily HU dose 950 mg). Median number of phlebotomies in the past 3 months prior to inclusion was 1 (range 0–8), a total of 21 patients (62%) were regularly phlebotomized at least once in three months prior to study entry. 11 patients (32%) had a history of thrombotic complications. Median Hct at baseline was 42% (range 36–51). Median WBC and platelet counts were 10.6*109/l (range 3.9–20.4) and 452*109/l (range 141–1019), respectively. 17 patients (50%) had splenomegaly at baseline. The median reported treatment duration was 41 weeks (range: 1 day – 80 weeks), 11 patients completed 1 year on treatment. Doses from 50 to 540 ug every two weeks were tested, 540 ug has been concluded as MTD as the highest tested dose, since no DLTs occurred in the study. The mean administered dose (both Phase I and II patients) was 287 ug. After 28 weeks of treatment (21 evaluable patients), 71% of patients had hematological response (7 CR, 33%; 8 PR, 38%), at week 36 (19 evaluable patients) 8 patients (42%) achieved a CR and 8 patients (42%) a PR, overall response rate (ORR, CR+PR) was 84%. At week 52 (1 year; 11 evaluable patients), 5 patients (46%) had CR and 5 (46%) PR, ORR was 91%; 8 (73%) patients presented with completely normalized blood values, all evaluable patients were phlebotomy free at this timepoint. 4 patients (of 12 evaluable for this measurement, 33%) had still enlarged spleen at week 52. At week 76, 2 evaluable patients were complete responders. At week 52, 1 patient (of 9 evaluable, 11%) developed partial molecular response, at week 68 3 patients (of 7 evaluable, 43%) had partial molecular response. One patient with allelic burden of 22% at baseline developed complete molecular response at week 36 (still ongoing). Mainly grade 1 and 2 adverse events were reported. A total of 358 adverse events occurred. 27 patients (79%) suffered from drug-related adverse events. 9 patients (26%) developed serious adverse events; 4 SAEs were considered to be treatment related. 5 patients (15%) discontinued their study participation prematurely, 3 of them due to adverse events (deterioration of underlying disease and two cases of depression). Acceptable tolerability and durable clinical benefits have been demonstrated in PV patients measured as overall response rate of above 90% with CRs of 46% at one year after treatment start. Phlebotomy independence and normalization of hematological parameters could be seen in most of the patients. The study continues to recruit and collect long term follow up information. Presented data support further development of AOP2014 in PV, a Phase III study is planned to start early 2013. Disclosures: Gisslinger: AOP Orphan Pharmaceuticals AG: Research Funding; Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Lechner:AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Tarmann:AOP Orphan Pharmaceuticals AG: Employment. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Zahriychuk:AOP Orphan Pharmaceuticals AG: Employment. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding.

Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 629-629 ◽  
Author(s):  
Nancy L. Bartlett ◽  
Mitchell R. Smith ◽  
Ranjana Advani ◽  
Tatyana Feldman ◽  
Kerry J. Savage ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Research Funding ◽  
Performance Status ◽  
Objective Response ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Frontline Treatment ◽  
Grade 3

Abstract Background Patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor outcome. In pts who progress <1 year after frontline treatment with rituximab-containing combination chemotherapy, response rates to salvage therapy and autologous stem cell transplant (SCT) are 46–51% with a 3-year event-free survival of ~20% (Gisselbrecht 2010). For pts ineligible for transplant, no standard of care exists and median overall survival for pts not responding to second-line therapy is only 4 months (Elstrom 2010). Novel therapeutic options are needed for these pts. A phase 2, open-label study was initiated to assess antitumor activity of brentuximab vedotin (ADCETRIS®), an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30+ non-Hodgkin lymphoma, including DLBCL. Significant antitumor activity was observed in DLBCL over a wide range of CD30 expression, including very low levels (<1–10%) as assessed by pathology at participating sites. As previously reported, 41% of DLBCL pts achieved an objective response (16% CR), regardless of CD30 expression (Bartlett, ASH 2013, Abstract 848). Subsequently, the trial was amended to investigate the antitumor activity of brentuximab vedotin in ~50 DLBCL pts with undetectable CD30 expression using standard immunohistochemistry (IHC) (NCT01421667). Preliminary results for this planned subset analysis of those pts are now available. Methods Eligible pts must have DLBCL with undetectable CD30 expression on tumor cells by visual assessment using routine IHC (anti-CD30 BerH2 antibody) per local lab. Pts must also have had 1–3 prior therapies and an ECOG performance status ≤2. Brentuximab vedotin 1.8 mg/kg is administered every 3 weeks until disease progression or unacceptable toxicity for pts who achieve stable disease or better. The primary endpoint is objective response rate per Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Key secondary endpoints include safety and duration of response. Results Thus far, 27 DLBCL pts with undetectable CD30 expression per local lab have been enrolled and treated. All patients had elevated soluble CD30 at baseline with a median of 166 ng/mL and range of 55–1,696 ng/mL (normal, ≤29 ng/mL). Most pts had advanced stage disease at baseline (78%); median age was 65 years (range, 42–91); and 81% had an ECOG performance status of 1–2. The median number of prior therapies was 2, and 8 pts had 3 prior therapies. Six (22%) pts had received prior autologous SCT. Of 14 pts (52%) with refractory disease at study entry, 11 were also refractory to their frontline treatment. To date, pts have received a median of 2 cycles of brentuximab vedotin (range, 1–10), and 12 (44%) pts remain on treatment. Thirteen pts discontinued treatment due to progressive disease, 1 withdrew consent, and 1 pt died due to an unrelated serious adverse event (SAE) of cardiac arrest. At the time of this analysis, 6 (27%) of 22 pts who have had restaging assessments achieved an objective response, including 1 CR and 5 PRs. The CR began at Cycle 6 and is ongoing after 9 weeks. It is too early to assess median response duration. For the 6 pts who achieved an objective response, undetectable CD30 was confirmed by central review. Peripheral sensory neuropathy and nausea were the most frequently occurring adverse events (AEs; 22% each). AEs ≥ Grade 3 occurring in more than 1 pt included hypokalemia, neutropenia (11% each), dehydration, diarrhea, nausea, and vomiting (7% each). All were Grade 3 in severity with the exception of 1 Grade 4 neutropenia. Four deaths occurred within 30 days of last dose; all were disease related except one due to cardiac arrest unrelated to study drug in a pt with prior cardiovascular disease and co-existing risk factors. Conclusions In this interim analysis of DLBCL pts with undetectable CD30, objective responses have been observed in 6 of 22 pts (27%) who have undergone restaging assessments. Safety data are consistent with historic results and pts continue to enroll on study. Activity of brentuximab vedotin in pts with undetectable CD30 by IHC may be explained wholly or in part by one of several factors, including tumor heterogeneity, levels of CD30 on tumor below the level of IHC sensitivity, uptake by cells in the tumor microenvironment that can release the cytotoxic payload, or deletion of repressive cells within the tumor microenvironment. Correlative work to better understand this activity is ongoing. Disclosures Bartlett: ImaginAb: Research Funding; Celgene: Research Funding; MedImmune: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Pfizer: Research Funding; Takeda Pharmaceuticals International Co.: Research Funding; Seattle Genetics, Inc.: Research Funding, Travel expenses Other; Janssen: Research Funding; Genentech: Research Funding; AstraZeneca: Research Funding. Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. Smith:Seattle Genetics, Inc.: Research Funding, Speakers Bureau. Advani:Janssen Pharmaceuticals: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Takeda International Pharmaceuticals Co.: Research Funding; Seattle Genetics, Inc.: Research Funding, Travel expenses Other. Feldman:Seattle Genetics, Inc.: Research Funding, Speakers Bureau. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Palanca-Wessels:Seattle Genetics, Inc.: Employment, Equity Ownership. Siddiqi:Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau.

scholarly journals SYK Inhibitor Entospletinib in Combination with Obinutuzumab Demonstrates Efficacy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4295-4295 ◽  
Author(s):  
Adam S. Kittai ◽  
Scott R Best ◽  
Bria Thurlow ◽  
Basak Gokcora ◽  
Andrzej Stadnik ◽  
...  
Keyword(s):  
T Cells ◽  
Phase I ◽  
Research Funding ◽  
Performance Status ◽  
Data Monitoring Committee ◽  
Ecog Performance Status ◽  
Bcr Signaling ◽  
Syk Inhibitor ◽  
Grade 3

B-cell receptor (BCR) signaling kinases are important targets in therapy of CLL. Resistance of lymphoid niche-resident CLL cells to BCR-signaling inhibition is fostered by the tumor microenvironment. We found that stromal B-cell activation factor (BAFF)-mediated activation of spleen tyrosine kinase (SYK) triggered BCR signaling, thereby contributing to apoptosis resistance in CLL cells (Paiva et al, 2017). The SYK inhibitor entospletinib (ENTO) abrogated BAFF-mediated BCR signaling accompanied by a decrease in pSTAT3 and MCL1 in vitro. We designed a Phase I/II investigator-sponsored trial of ENTO in combination with Obinutuzumab (Obin) in patients (pts) with relapsed/refractory CLL and non-Hodgkin lymphoma (NHL). Eligible pts were aged ≥18 years, had CLL/NHL (Phase I) or CLL (Phase II), relapsed and/or refractory to ≥1 prior therapies (no prior SYK inhibitor), ECOG performance status ≤2 and preserved organ function. The Phase I part of the study followed a standard 3+3 design with two dose levels (DL1: ENTO 200 mg PO BID; DL2 - ENTO 400 mg PO BID). ENTO was given for 7 days (run-in). Subsequently, Obin was given IV concurrently with ENTO on days 1, 2, 8, 15 of Cycle 1 and Day 1 of Cycles 2-6 in standard doses. ENTO was given until disease progression. Primary study objectives were toxicity (Phase I) and efficacy (objective response rate (ORR); Phase II). Correlative analysis of samples was performed at baseline, after run-in phase (7 days of entospletinib single agent) and after 6 cycles of combination therapy. Reverse protein phase array was performed at the RPPA core facility at MD Anderson Cancer Center. T cell populations and cytokine production were analyzed by flow cytometry. At DL1 of Phase I, six pts were enrolled (4 - CLL; 2 - follicular lymphoma). One pt experienced a dose-limiting toxicity (DLT: grade 3 asymptomatic LFT abnormalities which failed to resolve within 72 hours) attributed to ENTO. Other grade 3-4 toxicities included 2 grade 3 infusion reactions and one transient grade 4 neutropenia (attributed to Obin). Two pts remain on therapy after a median follow-up of 15 months. Three pts were enrolled at DL2 without DLTs. In Phase 2, 18 pts with CLL received ENTO 400 mg PO BID (in combination with Obin). One pt was deemed ineligible due to Richter's transformation at study entry. Of the 17 evaluable pts, 71% were men. Median age was 66 years (range 47-76), and 76% were aged >65 years. 94% had ECOG performance status ≤1. Six pts (35%) had a complex karyotype, 6 (35%) had a TP53 aberration, 2 - NOTCH1 and 3 - SF3B1 mutation. Median number of prior therapies was 2 (range, 1-6): 47% had received prior fludarabine, 53% - bendamustine, 35% - ibrutinib (5 pts with intolerance, 1 with progression). As of July 1, 2019, with median follow-up of 9.5 months (range, 3-17 months), 71% of pts remain on treatment. Median relative dose intensity of ENTO (ratio of actual to planned cumulative dose during drug exposure period) was 97%. ORR was 82%, 11 (65%) pts with partial response, three (17%) pts had CR (two MRD-negative in the bone marrow). All patients had a reduction in lymphadenopathy. Median duration of response and median progression-free survival (PFS) were not reached. All pts are alive. Five (29%) pts discontinued treatment (1 withdrawal of consent; 1 with recurrent LFT abnormalities; 1 for concomitant comorbidity and 2 with progression of disease). The most frequently occurring adverse events of all grades were infusion-related reactions, neutropenia and fatigue (Table). There were no Grade 5 events. Treatment with ENTO for 7 days during run-in phase led to downmodulation of pSTAT3 and MCL1 in CLL cells (RPPA assay), consistent with our pre-clinical observations. MCL1 has been previously implicated in survival of T cells at multiple stages of development. At the end of cycle 6, we observed a decrease in CD19+ and concomitant increase in CD3+ cells compared with baseline. There was no change in naïve, T-effector memory and T central memory cells within the CD4+ or CD8+ populations. Treatment with ENTO led to decreased PD-1 expression in CD4+ (22.6±3.8 vs. 31.5±5.4%, p=0.02) and CD8+ cells (p=0.05; Figure). Meanwhile, CTLA-4 expression was unchanged. PMA/ionomycin-stimulated CD4+ T cells demonstrated a decrease in IFNγ and IL-4. In summary, a combination of ENTO and Obin was effective and well tolerated in patients with R/R CLL, and was accompanied by downmodulation of MCL1 in CLL cells and PD-1 in T cells. Disclosures Persky: Debiopharm: Other: Member, Independent Data Monitoring Committee; Bayer: Consultancy; Sandoz: Consultancy; Morphosys: Other: Member, Independent Data Monitoring Committee. Spurgeon:Janssen: Research Funding; Astra Zeneca: Research Funding; Bayer: Other: drug support only, Research Funding; Ariad: Other: drug support only, Research Funding; KITE: Other: drug support only, Research Funding; Acerta: Research Funding; Bristol Myers Squibb: Research Funding; Genentech: Honoraria, Research Funding; Novartis: Other: drug support only, Research Funding. Danilov:Gilead Sciences: Consultancy, Research Funding; Abbvie: Consultancy; Takeda Oncology: Research Funding; Bristol-Meyers Squibb: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Aptose Biosciences: Research Funding; AstraZeneca: Consultancy, Research Funding; MEI: Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy. OffLabel Disclosure: Entospletinib in CLL

scholarly journals Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing after, or Are Refractory to, Hypomethylating Agent (HMA) Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3166-3166 ◽  
Author(s):  
Elias J. Jabbour ◽  
Hagop M. Kantarjian ◽  
Koji Sasaki ◽  
Tapan M. Kadia ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Research Funding ◽  
Low Dose ◽  
Group Performance ◽  
Performance Status ◽  
Advisory Board ◽  
Cell Transplant ◽  
Complex Karyotype ◽  
Overall Response ◽  
Low Dose Cytarabine

Abstract Background: HMA therapy is standard of care for patients with MDS. Outcome post HMA failure is poor with a median survival of 4-6 months. Clofarabine is a second generation nucleoside analog with single agent activity in MDS. The objective of this phase II trial is to evaluate the safety and activity of the combination of clofarabine and low dose cytarabine in the treatment of patients with high risk MDS who failed prior HMA therapy. Methods: Eligible patients were adults older than 18 years with MDS intermediate-1 and higher by the IPSS, who have had no response, progressed, or relapsed following at least 4 cycles of therapy with either azacitidine and/or decitabine. Patients were required to have an Eastern Cooperative Oncology Group performance status of </=2 at the time of study entry. Responses were defined according to International Working Group 2006 criteria. Induction therapy consisted of clofarabine 10-15 mg/m2 IV daily X 5 days (days 1-5) and cytarabine 20 mg SC twice daily X 7 days (days 1-7). Patients could receive up to 3 induction cycles as long as they tolerated the therapy and had stable disease. Responding patients proceeded with consolidation therapy with clofarabine 10-15 mg/m2IV daily X 3 days (days 1-3) and cytarabine 20 mg SC twice daily X 5 days (days 1-5) for a maximum of 12 cycles. Cycles were repeated every 4 to 8 weeks depending on hematopoietic recovery and resolution of toxicities. Results: From January 2012 to August 2015, 80 eligible patients were enrolled in this prospective study (NCT01444742) and received a median of 2 cycles (range, 1-12) (Table 1). The overall response rate (ORR) was 46% (16 [20%] achieved complete remission (CR), 17 [21%] marrow CR, 1 [1%] partial response (PR), 3 [4%] hematological improvement (HI)) with a median response duration of 7 months. The median time to response was 42 days (range, 9-191). By multivariate analysis, complex karyotype was the only independent factor predicting for response (hazard ratio [HR] 0.13; 95% confidence interval [CI]: 0.03- 0.62; p=0.01). Of the 37 patients with diploid karyotype, the overall response was 68% (7 [19%] achieved CR, 15 [41%] marrow CR, 1 [3%] PR, 3 [4%] HI). Nine of the responding patients received subsequent allogeneic stem cell transplant (ASCT). With a median follow-up of 24 months (range: 1-51 months), the median event-free survival (EFS) and overall survival (OS) times were 5 months (95% CI: 2.7-6.3) and 11 months (95% CI: 6.5-14.9), respectively (Figure 1). The median OS for responding and non-responding patients was 24 months (95% CI: 11.7-35.6) and 5 months (95% CI: 2.8-6.2), respectively (p<0.001). There was no difference in OS whether patients were censored or not at the time of ASCT (p=0.463). At last follow-up, 22 patients (28%) remained alive: 1 is receiving low-dose clofarabine and cytarabine, 5 are alive in response after ASCT, 9 are receiving salvage therapy, 1 went to hospice, and 6 were lost to follow-up. By multivariate analyses, complex karyotype, platelet count less than 30 x 109/L, and poor performance status were independently associated with poor survival. In addition, the response to the combination of low-dose clofarabine and cytarabine was independently associated with better OS (HR 0.17; 95% CI 0.09-0.36; p<0.001). Grade ≥ 3 therapy-related toxicity included infections (34%), increased liver functional tests (8%), acute renal failure (3%), skin rash (3%), syncope (1%), and rectal bleeding (1%). Twenty-two (28%) patients had clofarabine dose reduction after a median of 2 courses. After 47 patients were enrolled and several patients experienced infections during induction, the protocol was amended to reduce the dose of clofarabine to 10 mg/m2 per day for 5 and 3 days during the induction and consolidation phases, respectively. There was no difference in responses before and after the modification to the protocol's dosing schedule (p=0.314). Conclusion: The combination of low-dose clofarabine and cytarabine in patients with higher-risk MDS after HMA failure resulted in an ORR of 46% and median OS of 11 months and may be particularly effective in patients with diploid karyotype. Our results also indicate that the combination of low-dose clofarabine and cytarabine may be useful as a bridge to ASCT in eligible patients. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Jain:Abbvie: Research Funding; Infinity: Research Funding; Servier: Consultancy, Honoraria; Incyte: Research Funding; Genentech: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Novimmune: Consultancy, Honoraria; BMS: Research Funding. DiNardo:Agios: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Konopleva:Cellectis: Research Funding; Calithera: Research Funding.

Phase I/II study of GM-CSF gene-transduced allogeneic prostate cancer cellular immunotherapy (GVAX IT) in advanced prostate cancer patients made lymphopenic by chemotherapy and infused with autologous peripheral blood mononuclear cells (MC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14635-14635 ◽  
Author(s):  
B. D. Curti ◽  
I. Assman ◽  
T. Moudgil ◽  
T. Ratzow ◽  
D. Haley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Mononuclear Cells ◽  
Performance Status ◽  
Study Groups ◽  
Phase Iii ◽  
Cellular Immunotherapy ◽  
Ecog Performance Status ◽  
Peripheral Blood Mononuclear ◽  
Pre Treatment

14635 Background: GVAX IT has been tested in phase I/ II and is currently being tested in phase III clinical trials of patients (pts) with androgen-independent prostate carcinoma (AIPC). Immunological and PSA responses have been described in men receiving GVAX IT. Preclinical studies have shown that antitumor immune responses induced by GVAX IT could be augmented further by making animals lymphopenic and reconstituting with lymphocytes prior to vaccination. A clinical trial was designed to study the effects of lymphopenic reconstitution in pts with AIPC. Methods: All pts had MC collection by leukapheresis pre-treatment. Study groups were as follows: Arm A - GVAX IT given every two weeks for 6 months; Arm B - Cyclophosphamide (350 mg/m2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months; Arm C - Cyclophosphamide (350 mg/m2 IV on days 1–3) and fludarabine (20 mg/m2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months. Results: Seven pts have been treated thus far and completed at least 2 GVAX IT treatments. Pts had ECOG performance status ≤ 1, castrate testosterone levels, ≤ 1 prior chemotherapy regimen and measurable or evaluable metastatic AIPC. Lymphopenia was induced in all pts enrolled in Arms B and C, with recovery of total granulocytes and lymphocytes within 4 weeks following treatment. Monitoring of humoral and cellular immunological responses is underway and shall be presented. Conclusions: GVAX IT and lymphopenic reconstitution is feasible in men with AIPC. Analysis of clinical and immune response is ongoing. Supported by DAMD grant PC020094 and generous support of Mr. Tom Denhart, the Chiles Foundation and the Murdock Trust. [Table: see text]

Phase I/II study of percutaneous vertebroplasty (PVP) for painful malignant vertebral compression fracture(PMVCF): JIVROSG- 0202

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9118-9118
Author(s):  
Y. Arai ◽  
K. Kobayashi ◽  
Y. Takeuchi ◽  
Y. Nakajima ◽  
Y. Shioyama ◽  
...  
Keyword(s):  
Phase I ◽  
Treatment Modality ◽  
Response Rate ◽  
Bone Biopsy ◽  
Performance Status ◽  
Compression Fracture ◽  
Phase Iii ◽  
Increase Response Rate ◽  
Ecog Performance Status ◽  
Safety And Efficacy

9118 Backgrounds: This multi-center prospective study was conducted to evaluate the safety and efficacy of PVP, a new treatment modality for PMVCF, using techniques of interventional radiology. Methods: Enrolled patients (pts) had PMVCF by primary or metastatic tumor; restricted activities by PMVCF; tumor not exposed into spinal canal; adequate hematologic, hepatic, renal and cardiac functions; 0–3 ECOG performance status (PS); estimated prognosis over 4 weeks; and written consent. In phase I, 9 pts were enrolled; in phase II, 24 pts. Safety and efficacy were evaluated by NCI-CTC Ver. 2 and Visual Analogue Scale (VAS) at week 1 after PVP, respectively. By VAS score decreases, efficacy was classified into significantly effective (SE: =5 or reached 0–2), moderately effective (ME: 2–4), or not effective (NE: <2 or increase). Response rate was the ratio of pts with SE or ME in total pts. PVP was performed by insertion of 14–16 G bone biopsy needle into fractured vertebral body (FVB) using fluoroscopy or CT guidance, injection of bone cement (BC) under real time imaging observation, and discontinuation of BC injection at its distribution to adequate area of FVB or into extra bone space. Results: Procedures were completed in all 33 patients with 42 PMVCF. PS of pts was 0 in 1, 1 in 7, 2 in 12 and 3 in 13. In 30 days after PVP, 2 patients died of primary disease progression, but no major adverse reaction (>Grade 2) was observed. Response rate was 73% (56–85% in 95% CI) (61% (n=20) with SE; 12% (n=4) with ME; 27% (n=9) with NE), and increased to 83% at week 4. Median to PVP effect was 1 day (mean: 2.4). Median pain controlled survival was 73 days. Conclusion: For PMVCF, PVP is a safe and effective treatment modality with immediate responses. A phase III trial comparing PVP and standard radiation therapy is planned to evaluate PVP as the front line treatment. No significant financial relationships to disclose.

Clofarabine, Idarubicin, and Cytarabine (CIA) As Frontline Therapy for Patients <= 60 Years with Newly Diagnosed Acute Myeloid Leukemia (AML)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 43-43
Author(s):  
Aziz Nazha ◽  
Farhad Ravandi ◽  
Hagop M. Kantarjian ◽  
Xuelin Huang ◽  
Sangbum Choi ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Hepatic Function ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Overall Response

Abstract Abstract 43 Background Clofarabine is a second generation nucleoside analogue with activity in adults with AML. A recent randomized phase III study in relapsed AML showed higher response rates and better event-free survival (EFS) with the combination of clofarabine and cytarabine (CA) compared to cytarabine alone. A phase I/II trial of CIA in patients with relapsed/refractory AML had shown an overall response rate (ORR) of 38% (21% CR; 11% CRp). To explore this combination further, we conducted a phase II study of CIA in patients </= 60 years with previously untreated AML. Patients and Methods Eligible were patients >18–60 years with newly diagnosed AML and adequate renal and hepatic function. Patients were excluded for ECOG PS > 2, cardiac ejection fraction < 45%, or active and uncontrolled infection. For the first 30 patients, induction therapy consisted of Clofarabine (C) 22.5 mg/m2 iv daily (days 1–5), Idarubicin (I) 6 mg/m2 daily (days 1–3), and Cytarabine (A) 0.75 g/m2 daily (days 1–5). From patients 31 onward, induction doses were amended to C 20 mg/m2 × 5, I 10 mg/m2 × 3, and A 1 g/m2 × 5. Patients who did not achieve CR following induction could receive one re-induction course. Patients in CR/CRp/CRi continued with up to 6 consolidation cycles (C 22.5 mg/m2 × 3, I 6 mg/m2 × 2, and A 0.75 g/m2 × 3, subsequently amended to C 15 mg/m2 × 3, I 8 mg/m2 × 2, and A 0.75 g/m2 × 3). Results From April 2010 until February 2012, 59 patients were enrolled (Table 1). Fifty-seven patients were evaluable. Forty-two patients (74%) achieved CR and 3 (5%) CRp for an overall response rate of 79%. Ten patients required a re-induction {4/10 (40%) patients achieved CR, 2/10 (20%) achieved CRp). All patients received a median of 2 cycles (1–8 cycles), 24 (42 %) patients proceeded with an allogeneic stem cell transplant in first remission. With a median follow up of 10.9 months (1.6 - 23.1), the median OS was not reached, the median EFS was 13.5 months, and the median relapse free survival was not reached. Most toxicities were < grade 2. Toxicities > grade 2 included nausea (47%), rash (39 %), diarrhea (25%), elevated transaminases (23%), and elevated bilirubin (12%). Myelosuppression was ubiquitous but prolonged myelosuppression > 42 days was infrequent. Four week mortality was 2%. The response rate and toxicity were similar in both dose schedules. In subgroup analysis, patients < 40 years had better OS (HR 0.12, 95%CI, 0.02–0.90, P = 0.04) and EFS (HR 0.12, 95%CI, 0.02–0.93, P = 0.04) compared to patients > 40 years old. Compared to a historical group of patients who were treated with IA combination (I 12 mg/m2 IV daily × 3 plus A 1.5 g/m2 IV daily × 4) and after controlling for age, cytogenetics and other important clinical factors, the OS and EFS were significantly higher (P = 0.005, 0.0001, respectively) for CIA treated patients. Furthermore, in multivariate analysis, CIA retained its superior impact on OS (HR 0.53, 95% CI, 0.29 to 0.97, P =0.03) and EFS (HR 0.40, 95% CI, 0.22 to 0.73, P =0.003) compared to IA. Conclusion CIA is an active combination for patients </= 60 years with newly diagnosed AML. Patients < 40 years had significantly better OS and EFS. Compared to IA alone, CIA achieved significantly longer OS and EFS. A randomized comparison with standard induction therapy will be needed to further assess the role of CIA in frontline AML therapy of younger patients. Disclosures: Off Label Use: Clofarabine in AML. Ravandi:Genzyme: Research Funding. Kantarjian:Genzyme: Research Funding. Faderl:Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Phase I/II Trial of Bendamustine, Ixazomib and Dexamethasone (BID) in Patients (pts.) with Relapsed/Refractory Multiple Myeloma (RRMM)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1998-1998
Author(s):  
Binod Dhakal ◽  
Anita D'Souza ◽  
Mehdi Hamadani ◽  
Carlos E. Arce-Lara ◽  
Katrina Schroeder ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Phase Ii ◽  
Research Funding ◽  
Response Rates ◽  
Primary Objective ◽  
Cell Transplant ◽  
Open Label ◽  
Overall Response ◽  
Equity Ownership

Abstract Background: Bendamustine, a bifunctional alkylator with antimetabolite activity, is an attractive combination partner for both proteasome inhibitors (PI) and immunomodulators (ImiDs) in pts. with MM. This phase I/II trial assessed the safety and efficacy of the combination of BID in pts. with RRMM exposed to bortezomib and lenalidomide and refractory to at least one of the agents. Methods: This open label phase I/II study assessed the safety, tolerability and efficacy of BID regimen delivered in a 28-day cycle in RRMM. The primary objective of the phase I portion was to determine the recommended phase II dose (RP2D) of BID, and primary objective of the phase II portion was to estimate the overall response rates (ORR) of the combination. A 3+3 dose escalation based on dose limiting toxicities (DLTs) was employed in phase I; bendamustine was given at escalated doses of 70, 80 and 90 mg/m2 on days 1,2 of each cycle with ixazomib (4mg) and dexamethasone (40 mg) on days 1,8, 15 in a 28-day cycle for 4 cycles (up to 8 in responders). In phase II, an expansion cohort was enrolled at the RP2D using Simon 2-stage design. Results: A total of 28 pts. were enrolled between October 2015 January 2018. Median age of the pts. was 67 yrs. (range, 42-72), and 43% were females (Table 1). Patients received a median of 4 (range, 4-9) prior lines of therapy, of which 46% and 25% were double and quadruple refractory patients respectively and 89% had prior autologous stem cell transplant. Fifteen pts. were enrolled in phase I, and no DLTs were observed at dose level (DL) 1 and 2; while 2 /6 patients developed DLTs (neutropenia and thrombocytopenia) at DL3 establishing RP2D as bendamustine 80 mg/m2, ixazomib 4 mg and dexamethasone 40 mg. Additional 13 pts. were enrolled in phase II, and total of 19 pts. were available for phase II evaluation including pts. treated at maximal tolerated dose (MTD) in phase I (N= 6). Of 19, 18 pts. were evaluable for response per study definition, out of which 7 completed total of 8 cycles. The median number of cycles completed was 4 (1-8). The overall response rates (ORR) was 61% with very good partial response (VGPR) 2 (11%), partial response (PR) 9(50%) and stable disease (SD) 8 (44%) and progressive disease (PD) 2 (11%). One patient completed less than 1 cycle and not evaluable for response (Table 2). For responders, the median duration of response was 5.5 months (2-13). At a median follow up of 10 months, median progression free (PFS) and overall (OS) survival were 4 months (range, 1- 13) and 9 months (range, 1-15) respectively with no treatment related morality (Table 2). The most frequent adverse events were anemia, thrombocytopenia, leukopenia, nausea, diarrhea and infections. Treatment emergent ≥ grade 3 peripheral neuropathy was not seen. Conclusions: BID is a well-tolerated and effective combination therapy for pts. with heavily treated RRMM. Planned maintenance therapy was not used in this study and might be effective for prolonging responses. Disclosures Dhakal: Celgene: Consultancy, Honoraria; Takeda: Honoraria, Research Funding; Amgen: Honoraria. D'Souza:Celgene: Research Funding; Merck: Research Funding; Prothena: Consultancy, Research Funding; Takeda: Research Funding; Amgen: Research Funding. Hamadani:Merck: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; ADC Therapeutics: Research Funding; MedImmune: Consultancy, Research Funding; Ostuka: Research Funding; Celgene Corporation: Consultancy; Cellerant: Consultancy; Takeda: Research Funding; Janssen: Consultancy. Shah:Miltenyi: Other: Travel funding, Research Funding; Geron: Equity Ownership; Exelexis: Equity Ownership; Juno Pharmaceuticals: Honoraria; Oncosec: Equity Ownership; Lentigen Technology: Research Funding. Hari:Celgene: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Spectrum: Consultancy, Research Funding; Kite Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Honoraria; Sanofi: Honoraria, Research Funding.

A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies

2020 ◽  
Vol 7 (2) ◽  
pp. 125-132
Author(s):  
Karen A. Gelmon ◽  
Christian Kollmannsberger ◽  
Stephen Chia ◽  
Anna V. Tinker ◽  
Teresa Mitchell ◽  
...  
Keyword(s):  
Phase I ◽  
Salvia Miltiorrhiza ◽  
Performance Status ◽  
Parent Drug ◽  
Maximum Tolerated Dose ◽  
Ecog Performance Status ◽  
Advanced Malignancies ◽  
Gi Toxicity ◽  
Adequate Organ Function ◽  
Recommended Phase Ii Dose

Background/Objective: With the increasing interest in natural products, a phase I openlabel study of OMN54 (Aneustat™) in patients with advanced malignancies was initiated to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent, combining three Chinese botanicals; Ganoderma lucidium, Salvia miltiorrhiza and Scutellaria barbata. Methods: Eligible patients (pts) were >18 years of age with advanced solid tumors, able to swallow oral capsules, ECOG performance status < 2, measurable disease as defined by RECIST 1.1 and adequate organ function. Results: Twenty-two patients were enrolled in 6 dose levels, 2 with daily dosing and 4 with twicedaily dosing ranging from 1 to 5 grams daily. All were evaluated for toxicity and 20 for response. No treatment-related dose-limiting toxicities (DLTs) were reported and the recommended phase II dose (RP2D) was determined to be 2.5 g twice daily. Seven adverse events in 5 patients were reported as possibly drug-related; 6 were GI toxicity and 1 was a skin disorder. All were grade 1 except one grade 2 vomiting. No RECIST responses were seen. Six pts were treated with > 2 cycles; one for 8 cycles. Four patients had reductions in TGF –β and EGF, exploratory biomarkers possibly suggestive of a drug effect. Plasma half-lives of 1 -2 hours were noted for all parent drug chemical markers with no accumulation over time. Conclusion: OMN54 was well tolerated, with no DLTs observed. Further studies at the RP2D will assess the biological activity.

scholarly journals Long Term Outcome of Lenalidomide-Dexamethasone (Rd) Vs Melphalan-Lenalidomide-Prednisone (MPR) Vs Cyclophosphamide-Prednisone-Lenalidomide (CPR) As Induction Followed By Lenalidomide-Prednisone (RP) Vs Lenalidomide (R) As Maintenance in a Community-Based Newly Diagnosed Myeloma Population: Updated Analysis of EMN01 Phase III Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 901-901
Author(s):  
Sara Bringhen ◽  
Massimo Offidani ◽  
Pellegrino Musto ◽  
Anna Marina Liberati ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Community Based ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Grade 3 ◽  
To Receive

Abstract Introduction : Rd and MPR showed to be effective combinations in elderly newly diagnosed multiple myeloma (NDMM) patients (pts). Cyclophosphamide is a less toxic alkylating alternative agent. EMN01 is the first trial to formally compare these three different Lenalidomide-based combinations. Maintenance with Lenalidomide has been recently approved in patients eligible for autologous stem cell transplant (ASCT). Few data are available about the best combination as maintenance in patients not eligible for ASCT. Methods : 662 pts with NDMM were randomized to receive 9 28-day cycles of Rd (lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15 and 22 in pts 65-75 years old and 20 mg in those &gt;75 years), MPR (lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in pts 65-75 years old and 0.13 mg/Kg in &gt;75 years pts; prednisone 1.5 mg/Kg for 4 days) or CPR (lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in pts 65-75 years old and 50 mg every other day in &gt;75 years pts; prednisone 25 mg every other day). After induction, pts were randomized to receive maintenance with lenalidomide alone (R; 10 mg/day for 21 days) or with prednisone (RP; R, 10 mg/day for 21 days and P, 25 mg every other day), until disease progression. Results : Pts characteristics were well balanced in all groups; 217 pts in Rd, 217 in MPR and 220 in CPR arms could be evaluated. After a median follow-up of 63.7 months, median PFS was 23.2 months in MPR, 18.9 months in CPR and 18.6 months in Rd (MPR vs CPR p=0.02; MPR vs Rd p=0.08). Median overall survival (OS) was 79.9 months in MPR, 69.4 months in CPR and 68.1 months in Rd (MPR vs CPR p=0.98; MPR vs Rd p=0.64). The most common grade ≥3 adverse event (AEs) was neutropenia: 64% in MPR, 29% in CPR and 25% in Rd pts (p&lt;0.0001). Grade ≥3 non hematologic AEs were similar among arms. At the end of induction, 402 pts were eligible for maintenance, 198 in the RP and 204 in the R groups. PFS from start of maintenance was 22.2 months in the RP group and 17.6 in the R group, with 20% reduced the risk of death/progression for pts receiving RP maintenance (HR 0.81, p=0.07; Figure 1). A subgroup analysis was performed to determine the consistency of RP vs R treatment effect in different subgroups using interaction terms between treatment and cytogenetic abnormalities, ISS, age, sex, induction treatment and response before maintenance (Figure 1). No difference in OS was observed (HR 1.02, p=0.93) but the OS analysis was limited by the low number of events. Median duration of maintenance was 23.0 months in RP pts and 20.5 months in R pts, 14% and 13% of pts discontinued due to AEs, in RP and R groups, respectively. Conclusion : This phase III trial compared 2 different Lenalidomide-containing induction regimens and 2 different Lenalidomide-containing maintenance regimens in an elderly community-based NDMM population. MPR prolonged PFS by approximately 5 months, yet the higher incidence of hematologic toxicity should be carefully considered. The addition of low-dose prednisone to standard lenalidomide maintenance reduced the risk of death/progression by 20%, with a good safety profile. Updated results will be presented at the meeting. Disclosures Bringhen: Mundipharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Karyipharm: Membership on an entity's Board of Directors or advisory committees. Offidani: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto: Celgene: Honoraria; Janssen: Honoraria. Gaidano: Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. De Sabbata: Celgene: Membership on an entity's Board of Directors or advisory committees. Palumbo: Sanofi: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Binding Site: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Genmab A/S: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Employment, Equity Ownership, Honoraria, Research Funding. Hájek: Amgen, Takeda, BMS, Celgene, Novartis, Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Pharma MAR: Consultancy, Honoraria. Boccadoro: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

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