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In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 5 ( 2021-05), p. 1291-1300

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-020-01031-1

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2008023-2

In: British Journal of Haematology, Wiley, Vol. 151, No. 4 ( 2010-11), p. 365-375

Type of Medium: Online Resource

ISSN: 0007-1048

URL: Issue

URL: Article

DOI: 10.1111/bjh.2010.151.issue-4

DOI: 10.1111/j.1365-2141.2010.08381.x

Language: English

Publisher: Wiley

Publication Date: 2010

detail.hit.zdb_id: 1475751-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 14 ( 2023-05-10), p. 2607-2616

Abstract: Rituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM. METHODS In this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety. RESULTS Two hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC ( P = .32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P 〈 .01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade ≥ 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC. CONCLUSION This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.22.01805

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2023

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 32 ( 2018-11-10), p. 3203-3210

Abstract: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. Patients and Methods Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC] ). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. Results From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. Conclusion Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2018.78.7366

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2018

detail.hit.zdb_id: 2005181-5

In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 6 ( 2021-06), p. 1597-1609

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-020-01009-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2008023-2

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 25-26

Abstract: Background Ixazomib (IXA) is an orally-administered proteasome inhibitor approved in Europe in November 2016 for relapsed and/or refractory multiple myeloma (RRMM). It became available in France in May 2017 via a compassionate use program (CUP) and from October 2018 via the classical market access (non-CUP). In addition to pivotal clinical trials, real-world evidence (RWE) is required to evaluate effectiveness and safety in clinical routine practices. A non-interventional study, has been conducting in France to evaluate IXA use in combination with lenalidomide and dexamethasone (IRD) in real life. Methods REMIX is a non-interventional, multicentric study to assess IRD effectiveness and safety, conducted in 59 sites (public and private) in patients with RRMM. IRD was initiated in second line or more during the CUP and afterwards. After inclusion, patients were assessed every 3 months (mo) during 24 mo then every 6 mo as per standard practice. This interim analysis assessed IRD effectiveness (median Progression Free Survival (mPFS), 12 and 24-mo overall survival (OS) rates and tolerance in the CUP patients initiating IXA concomitantly to RD (patients who started lenalidomide more than 6 weeks before IXA were excluded). The analysis was conducted globally and per subgroups (age, number of lines of treatment, frailty as defined by Facon T & al.in Leukemia 2020). The CUP-patient median study follow-up was 17.4 mo for this interim analysis. Results The 198 eligible CUP patients were 47% of males, with a median age of 69 years (26% ≥75y). Out of them, 45% were frail and 7% had renal failure (CrCl ≤30 ml/min). Comorbidities were reported in 64% of patients including diabetes (9%), renal disease (10%), solid tumor (9%). At diagnosis, the cytogenetic risk was standard, high or unknown in respectively 46%, 13% and 41% of patients; 11% presented a plasmacytoma. 41% had multiple or severe bone lesions and 25% peripheral neuropathy. MM was diagnosed at a median of 4 years before IRD initiation. IXA was initiated after one (L2) / two (L3) / three or more lines of treatment (L4+) in respectively 58%, 18% and 24% of patients. Of them, 38% had received lenalidomide during prior line(s), mainly in patients with L3 and L4+ (78%, 65/84) vs L2 (8%, 9/114). The median washout period between lenalidomide discontinuation and IRD start was 18 mo 95%CI [17.6 - 29.6]. The mPFS was 19.2 mo 95%CI [13.3; 21.9] for the CUP cohort. mPFS was 21.5 mo 95%CI [13.3; 21.9] for L2 (104 patients), 17,8 mo 95%CI [12.2; 26.7] for L3 (29 patients) and 5.6 mo 95%CI [4.1; 8.8] for L4+ (38 patients) (c.f. Figure1). mPFS was similar in & lt;75 YO (19.2, mo 95%CI [12.3; 24.8]) and in ≥75 YO patients (19.2 mo, 95%CI [1.7; 21.5] ). In the subgroup with available frailty score (n= 124), mPFS was 21.5 mo 95%CI [12.5; -] in non-frail and 13.3 mo 95%CI [5.6 ; 19.8] ) in frail patients. 12mo and 24mo-OS rates were 84% 95%CI [78%; 89%] and 73% 95%CI [65%; 80%] for the global group. Among the 166 patients with available response according to investigators, overall response rate (ORR) was 68% (66% in & lt;75 YO and 71% in ≥75 YO patients) and very good partial response (VGPR) 35% (38% in & lt;75 YO and 27% in ≥75 YO patients). The 187 followed-up CUP patients received a median of 14 IRD cycles. IXA discontinuation was reported in 50% of patients (n=92), related to AE in 13% of cases (n= 24). Serious adverse events were reported in 34% (n=69), including 14 (7%) patients with SAE considered related to IXA. Most frequent ( & gt;10%) AE were thrombocytopenia (30%), diarrhoea (28%), asthenia (20%), anaemia (18%), neutropenia (15%), nausea (14%) and peripheral neuropathy (10%). Conclusion Few RWE data have been published for IXA use in Europe. In this first interim analysis, estimated mPFS is consistent with MM1 results or data reported in MM1 study (19,2 mo vs 20.6 mo) even though CUP patients in REMIX were globally elder, frailer and more frequently treated in advanced lines (24% of L4+ in REMIX vs 11% of L4 in MM1). Reported adverse events were in line with known safety IXA profile. Figure 1 Disclosures Laribi: abbvie: Honoraria, Research Funding; amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding. Vincent:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; janssen: Membership on an entity's Board of Directors or advisory committees, Other: Congress support. Hulin:Celgene/Bristol-Myers Squibb, Janssen, GlaxoSmithKline, and Takeda: Honoraria. Macro:sanofi: Honoraria; gsk: Honoraria; janssen: Honoraria, Other: travel accomodation, Research Funding; takeda: Honoraria, Other: travel accomodation, Research Funding. Karlin:Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Personal fees; Sanofi: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees. Texier:Kappa Santé: Other: employee of the CRO in charge of REMIX. Chouaid:pfizer: Honoraria, Research Funding; GSK: Honoraria, Research Funding; novartis: Honoraria, Research Funding; pfizer: Honoraria, Research Funding; takeda: Honoraria, Research Funding; bms: Honoraria, Research Funding; msd: Honoraria, Research Funding; astra zeneca: Consultancy, Honoraria, Research Funding; amgen: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding. Leleu:GSK: Honoraria; Amgen: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Oncopeptide: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; Novartis: Honoraria; AbbVie: Honoraria; Karyopharm: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-133807

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 26-26

Abstract: Background: Rituximab/chemotherapy is still one of the cornerstones of treatment for patients with Waldenström's macroglobulinemia (WM) despite the emergence of BTK inhibitors. Beside Rituximab-Bendamustine the combination Dexamethasone, Rituximab and Cyclophospamide (DRC) is the most widely recommended immunochemotherapy in national and international guidelines based on its low myelotoxicity and anti-lymphoma activity in WM. In addition, the proteasome inhibitor Bortezomib (B) has shown significant activity in WM as single agent or combined with Rituximab and/or Dexamethasone. This study aimed at evaluating the efficacy and toxicity of Bortezomib-DRC (B-DRC) as first line treatment in WM. Methods: In this prospective randomized multicenter European phase II study, patients with the diagnosis of WM confirmed by reference pathology and in need of treatment were randomized 1:1 to DRC (Dexamethasone 20 mg orally d1, Rituximab 375 mg/m2 IV d1 cycle 1 and 1400 mg SC d1 cycle 2-6, Cyclophosphamide 100 mg/m2 x 2 orally d1-5) or to B-DRC (DRC plus Bortezomib SC 1,6mg/m2 day 1, 8, 15) for 6 cycles (28d interval). Primary endpoint was progression free survival (PFS). Secondary endpoints included response rates, overall survival (OS), and toxicity. Results: Of 204 registered patients, 2 patients were excluded due to incorrect randomization. Median follow-up was 27.5 months at the time of the data cut. Median age was 68 years (range 34-89) in both arms. According to the ISSWM prognostic score 14 % of patients were at low, 73 % at intermediate and 13 % at high risk in both treatment arms. Median baseline hemoglobin for B-DRC and DRC was 10.0 and 9.8 g/dl and median baseline IgM 31.7 and 31.9 g/dl, respectively. Mutational status was available for 72 patients: in the B-DCR vs DRC treatment arm 26 and 16 patients were MYD88 mutated (MYD88MT) and CXCR4 wildtype (CXCR4WT), 8 and 12 patients were MYD88MT/CXCR4MT and 5 and 5 patients MYD88WT/CXCR4WT, respectively. Median PFS has not been reached in the B-DRC arm (95% CI: 33.5; --) compared to 50.1 months in the DRC arm (95% CI: 31.1; --) with an estimated PFS at 24 months of 80.6 % (95% CI: 69.5; 88.0) and 72.8 % (95% CI: 61.3; 81.3), respectively (p=0.32). Median OS has not been reached in either treatment arm with 5 deaths and 6 deaths in the B-DRC and DRC arm, respectively. At the end of treatment B-DRC induced major responses (at least PR) in 79.1 % of patients (vs 68.9% for DRC) and a CR/VGPR in 18.7 % of patients (vs 11.1 % for DRC) with an overall response of 91.2 compared to 86.7 % for DRC. Compared to baseline IgM decreased by 79 % and 73 % and Hb increased by 28 % and 32 % in the B-DRC and DRC arm, respectively. Responses and PFS were independent of the mutational status in both treatment arms. B-DRC and DRC were well tolerated: grade ≥3 AEs occurred in 48% of all patients (B-DRC 48%, DRC 47%). Most common grade ≥3 AEs included neutropenia (25%), anemia (6%), and thrombocytopenia (5%). Overall, 16 pts (8%) developed infections (1% grade ≥3). Serious AEs occurred in 40 pts (20%) (DRC: 26 (26%), B-DRC: 14 (14%)). Peripheral sensory neuropathy occurred in 18 patients treated with B-DRC (2 patients with grade 3, 16 patients grade 1-2) and in 3 patients treated with DRC (all grade 1 and 2). Conclusions: This is the first and largest prospective randomized trial to evaluate bortezomib in combination with standard immunochemotherapy, demonstrating that B-DRC is a well-tolerated regimen which induces a high rate of major responses including deep remissions after 6 months of treatment with a 2-year PFS of 81%, independently of the mutational status of MYD88 and CXCR4. At this time point of analysis, adding Bortezomib to DRC did not induce significant differences in PFS compared to DRC alone. Future trials will have to compare chemotherapy-free approaches such as continuous treatment with BTK inhibitors with fixed duration treatments exemplified by B-DRC to understand which of the two treatment approaches offers the highest long - term sustained clinical benefit to WM patients. Disclosures Buske: Roche, Janssen, Bayer, MSD: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, AbbVie, Pfizer, Celltrion: Honoraria, Speakers Bureau. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau. Kastritis:Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Tomowiak:Roche: Research Funding; Gilead: Research Funding; Janssen: Honoraria; AbbVie: Honoraria; Beigene: Honoraria; Takeda: Honoraria. Hajek:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; PharmaMar: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Oncopeptides: Consultancy. Viardot:Roche: Honoraria, Other: advisory board; Kite/Gilead: Honoraria, Other: advisory board; Novartis: Honoraria, Other: advisory board; Amgen: Honoraria, Other: advisory board. Aurran:Janssen: Honoraria. Lepretre:Gilead: Honoraria; Astra Zeneca: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Leblond:AbbVie: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria; Janssen: Honoraria; Roche: Honoraria; Astra Zeneca: Honoraria; Amgen: Honoraria; Gilead: Honoraria; Beigene: Honoraria; Beigene: Membership on an entity's Board of Directors or advisory committees. de Guibert:Gilead Sciences: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Garcia-Sanz:Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Gilead: Honoraria, Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Pharmacyclics: Honoraria; Takeda: Consultancy, Research Funding. Gomes da Silva:roche: Consultancy; abbvie: Consultancy; BMS: Consultancy; MSD: Consultancy; Janssen: Consultancy; Gilead: Consultancy. Morel:Janssen: Honoraria. OffLabel Disclosure: Bortezomib in combination with DRC in Waldenström's Macroglobulinemia

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-140933

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 467-467

Abstract: Background :AZA improves overall survival (OS) in higher risk MDS, but only 50-60% of the patients respond, and median OS with AZA is only 20-24 months. As OS improvement is obtained at modest response rates, OS rather than response should probably remain the primary endpoint for all combinations with AZA, requiring large phase III trials with significant follow up. On the other hand, combinations that do not increase response will likely not improve OS. We therefore tested, based on a "pick the winner" approach, AZA combinations with the HDAC inhibitor VPA, LEN or IDA to identify, based on response, the most promising combination with AZA in higher risk MDS, that could be subsequently compared with AZA alone in a larger phase III study. Methods : AZA-PLUS (#NCT01342692)was an adaptive two-stage phase II trial based on Jung design (Stat Med.2008;27:568) that randomly assigned higher-risk MDS, low blast count AML (20-30%) and CMML to: AZA (75 mg/m2/d d1-7 of 28-day cycles); AZA plus LEN (10 mg/d on d1-14); AZA plus VPA( 50 mg/kg/d on d1-7; 35 mg/kg/d in patients 〉 60y) or AZA plus IDA (10 mg/m2on d1 for the first 9 cycles). The primary end point was response rate (RR, including CR, PR, marrow CR, based on IWG 2006) of the combination arms vs AZA alone. Given a 30% RR with AZA alone, we considered that a ≥45% RR would make combination(s) promising. Controlling for type I and type II errors at 0.15 and 0.20, 40 patients per arm were to be enrolled at each stage. Any experimental arms with RR lower than those observed in the AZA arm at the first stage should be stopped. At the second stage, any arm with 〉 6 more responses than AZA alone should be selected for further testing. Secondary endpoint were ORR (RR+ stable disease with HI (HI) and OS. Results : After inclusion of 40 pts/arm (first stage) all experimental arms had at least the same number of responses as the control arm and were continued in second stage. Overall, 322 pts were enrolled from 06/2011 to 07/2017: 81, 80, 80, 81 in the AZA, AZA+VPA, AZA+LEN and AZA+IDA arms, respectively. Baseline characteristics were well-balanced across arms. Median age was 74.6 y, 213 pts were male, IPSS was INT-2 in 54% and High in 46%. IPSS Karyotype was fav, int and poor in 40%, 26% and 34%, respectively. Pts received a median of 7 cycles and median follow-up was 15.1 months. Prevalence of trial discontinuation due to adverse events was 32%, 29%, 28% and 31% in the AZA , AZA+VPA , AZA+LEN and AZA+IDA arms, respectively (p=0.95). Rates of hospitalization during the first 6 cycles were 38%, 44.7% , 55.1%, 59.7% in the AZA, AZA +VPA, AZA+LEN and AZA+IDA arms, respectively (p=0.028), suggesting increased myelosuppression in the experimental arms, especially in the LEN and IDA arm. In the control arm, 29 responses (CR+PR+mCR) after 6 cycles were observed, with 29, 25 and 29 responses observed in AZA+VPA , AZA+LEN and AZA+IDA arms, respectively. Thus, no combination demonstrated benefit over AZA. The RR was estimated at 34.8% (18.6% CR, 3.1% PR, and 13.0% mCR) and the ORR after 6 cycles was 40.4%. The RR after 6 cycles (35.8% for AZA, 36.2% for AZA+VPA, 31.2% for AZA+LEN, and 35.8% for AZA+IDA) and the ORR after 6 cycles (41.9% for AZA; 41.2% for AZA+VPA, 40.0% for AZA+LEN and 38.3% for AZA+IDA) were close across study arms. By multivariate analysis, factors associated with better ORR were higher Hb level (p=0.05), low fibrinogen (p=0.008) and low LDH (p=0.01). 17 (5%) pts were bridged to allogeneic SCT: 6 on AZA, 5 on AZA+VPA, none in the AZA+LEN arm and 6 on AZA+IDA arm (p=0.03). At the reference date of July 2018, median EFS was 16.6 months for in AZA, 14.5 months for in AZA+VPA, 15.1 months for in AZA+LEN and 13.2 months for in AZA+IDA (p=0.74) (Fig A). Multivariable Cox model selected Hb level (p=0.02), presence of circulating blasts (p 〈 0.0001), LDH (p=0.006) and high IPSS (p 〈 0.0001) as prognostic.Median OS was 24.5 months for AZA, 18.9 months for AZA+VPA, 17.5 months for AZA+LEN and 20.1 months for AZA+IDA (p=0.50) (Fig B). Factors associated with OS were circulating blasts (p=0.003) and high IPSS (p 〈 0.0001). Conclusion : Although OS differences may occur with longer follow up, the combination of VPA, LEN or IDA to AZA did not improve response or OS over AZA alone and worsened myelosuppression. With newer, potentially more potent drugs that can be combined with AZA, the "pick the winner " approach may still be useful to select promising combinations based on response in phase II trials. Molecular data of the pt cohort will be presented at the meeting. Figure. Figure. Disclosures Ades: silent pharma: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; JAZZ: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Laribi:Novartis: Other: Grant and personal fees; Sandoz: Other: Grant; Teva: Other: Grant; Hospira: Other: Grant; Takeda: Other: Grant and personal fees; Roche: Other: Grant; Amgen: Other: Personal fees; Gilead: Other: Personal fees. Stamatoullas:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Consultancy. Beyne-Rauzy:Novartis: Research Funding. Cluzeau:MENARINI: Consultancy; CELGENE: Consultancy; JAZZ PHARMA: Consultancy. Quesnel:Sunesis: Honoraria; Astellas: Honoraria; Novartis: Honoraria; Celyad: Honoraria. Fenaux:Jazz: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-111756

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 4312-4314

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-157942

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 2302-2305

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-165217

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7