ALBERT

Description: Abstract 324 Introduction and classification: This is the largest adult T-ALL cohort treated according to immunologic subtypes. All patients were immunophenotyped in one central lab (Berlin). T-ALL (cyCD3+, CD7+) were subclassified into early T-ALL (sCD3-, CD1a-), thymic T-ALL (sCD3-/+, CD1a+) and mature T-ALL (sCD3+, CD1a-). T-ALL constitutes in 3 consecutive GMALL-studies 24% of ALL patients. Patients and methods: A total of 744 T-ALL pts (15 to 55 yrs) were accrued in 102 hospitals in the GMALL studies 05/93, 06/99 and 07/2003. In GMALL 05/93 239 adult T-ALL patients, were treated according to a multi-agent chemoprotocol. Stem cell transplantation (SCT) was not recommended in CR1. In GMALL studies 06/99 and 07/03 505 T-ALL pts received intensified chemotherapy; particularly with introduction of PEG-asparaginase in induction as well as HDMTX/PEG-Asp consolidation cycles. Based on study 05/93 results, SCT from sibling (Sib) as well as matched unrelated (MUD) donor in CR1 was recommended for all patients with early T-ALL, mature T-ALL and for high-risk (HR) pts with thymic T-ALL (defined as late CR, complex karyotype or MRD positivity (MRD+)). Results: T-ALL subtype distribution in the total cohort of 744 adult T-ALL was early-T 23% (N=170), thymic-T 56% (N=420), mature-T 21% (N=154), without any differences between the studies. GMALL Study 05/93: The overall CR rate was 86% (early-T 72%, thymic-T 93%, mature-T 84%. The lower CR rate in early T-ALL was mainly due to early death (19%). The overall CCR rate was 47% (early-T 45%, thymic-T 54%, mature-T 30%). The overall survival rate at 10 yrs for all pts was 47% (early-T 47%, thymic-T 55%, mature-T 25%). GMALL Study 06/99 and 07/03: Of the 505 patients, 87% achieved CR (early-T 84%, thymic-T 92%, mature-T 77%). PR/Failure was higher in early-T (13%) and mature-T (17%) compared to thymic-T (5%). Early death was 4% and equally distributed. 267 pts (64%) received chemotherapy only and the majority were 229 pts (86%) with thymic T-ALL, not considered for SCT in CR1. The CCR rate was 61%. The few early (n = 15) and mature (n = 23) T-ALL pts, which could not have a transplant in CR1, are a negative selection (e.g. early relapse, comorbidity, no donor) and their CCR rate was 33% and 22% respectively. This was due to a high relapse rate in early T-ALL (60%) and mature-T (74%) compared to 33% in thymic-T. Overall survival rate at 8 yrs for thymic T-ALL with chemotherapy was 68%, for the 77 adolescent pts (15 to 25 yrs) even 76%. Stem cell transplantation: 153 T-ALL pts in studies 06/99 and 07/03 received a SCT in first remission. SCT realisation rate in early T-ALL was 84%, in mature-T 68%. Overall CCR rate was 58% (early-T 47%, HR thymic-T 79%, mature-T 61%). Relapse rate after SCT was in early-T 33% and in mature-T 22%. The overall TRM rate was 18% despite more than half MUD SCT, without any TRM difference between the immunological subtypes. Overall survival rate after SCT in CR1 at 8 yrs was 53%, early-T 44%, thymic-T 67%, mature-T 59%. SCT modalit: 49% received alloSib, 55% alloMUD and 20% auto-SCT. Overall CCR rate after alloSib for the total cohort was 65% (early-T 60%, thymic-T 73% and mature-T 69%); for alloMUD total 55% (early-T 45%, thymic-T 77%, mature-T 61%) and for the small cohort of 20 pts with auto-SCT CCR was 35%. Conclusion: The strategy in three consecutive GMALL studies to stratify and treat adult T-ALL pts according to the immunologic T-subtypes was successful. Overall survival at 5 yrs could be improved to 56% from 44%. There was a particular improvement for mature T-ALL (49% vs. 30%) and early-T (40% vs. 33%). This was mainly due to a high realisation rate of SCT in early T-ALL and mature T-ALL and the substantial better results of SCT. Results of alloMUD SCT were comparable to alloSib SCT. The small cohort of HR thymic T-ALL pts also had a benefit from SCT. The excellent outcome of SR thymic T-ALL (∼ 50% of all T-ALL) with the OS of 68% and 76% in adolescents due to intensified chemo, partic. PEG-Asp, does not suggest SCT in CR1. Several molecular markers, such as ERG, BAALC, WT1, had in a retrospective analysis some prognostic relevance in this pt cohort. The new GMALL study generation will however focus in thymic T-ALL on early evaluation of MRD to decide for SCT (MRD+) or not (MRD-) whereas early/mature T-ALL remain allocated to high risk groups with SCT in CR1. Supported by Deutsche Krebshilfe 702657Ho2 and BMBF 01GI9971/8 Disclosures: No relevant conflicts of interest to declare.

Description: Monitoring of measurable residual disease (MRD) provides prognostic information in patients with Nucleophosmin1 mutated (NPM1mut) acute myeloid leukemia (AML) and represents a powerful tool to evaluate treatment effects within clinical trials. We determined NPM1mut transcript levels (TL) by RQ-PCR and evaluated the prognostic impact of NPM1mut MRD and the effect of gemtuzumab ozogamicin (GO) on NPM1mut TL and the cumulative incidence of relapse (CIR) in patients with NPM1mut AML enrolled in the randomized phase III AMLSG 09-09 trial. 3733 bone marrow (BM) and 3793 peripheral blood (PB) samples from 469 patients were analyzed. NPM1mut TL log10 reduction ≥3 and achievement of MRD negativity in BM and PB were significantly associated with a lower CIR rate, after two treatment cycles and at end of treatment (EOT). In multivariate analyses, MRD positivity consistently revealed as poor prognostic factor in BM and PB. With regard to treatment effect, the median NPM1mut TL were significantly lower in the GO-Arm across all treatment cycles, resulting in a significantly higher proportion of patients achieving MRD negativity at EOT (56% vs 41%; P=.01). The betterreduction of NPM1mut TL after two treatment cycles in MRD-positive patients by the addition of GO led to a significantly lower CIR rate (4-year CIR 29.3% vs 45.7%, P=.009). In conclusion, the addition of GO to intensive chemotherapy in NPM1mut AML resulted in a significantly better reduction of NPM1mut TL across all treatment cycles leading to a significantly lower relapse rate. The AMLSG 09-09 trial was registered at www.clinicaltrials.gov as #NCT00893399.

Description: Background: Patients with primary refractory acute myeloid leukemia (AML) have a dismal outcome. Only allogeneic stem cell transplantion (SCT) currently offers the chance of cure to these patients. In order to improve outcome after allogeneic SCT, one important prerequisite is to increase response rates prior to SCT. Aims: To evaluate the impact of all-trans retinoic acid (ATRA) and gemtuzumab ozogamicin (GO) given as adjunct to high-dose cytarabine-based salvage therapy in younger adult patients with primary refractory AML on achievement of response. Consecutive allogeneic SCT was intended in all patients. Methods: Main inclusion criteria of the AMLSG 05-04 trial (NCT00143975) were refractory AML following one cycle of ICE (idarubicin, cytarabine, etoposide); and age 18 to 60 years. Dose and schedule of the GO-A-HAM regimen were as follows: GO 3mg/m2, day 1; cytarabine 3g/m2 bid., days 1–3; mitoxantrone 12mg/m2, days 2,3; ATRA 45mg/m2, days 3–5, 15mg/m2 days 6–28. Primary endpoint of the study was CR rate. Safety endpoints comprised early / hypoplastic (ED/HD) death rate, liver toxicity CTC grade 3–5, and rate of veno occlusive disease (VOD) after allogeneic SCT. Results: Between September 2004 and June 2007, 94 patients (median age, 48 yrs; range, 22 to 62) were enrolled. Distribution of cytogenetics was as follows: adverse, n=29 [abn(3q), −5/5q-, −7/7q-, abn(12p), abn(17p), complex]; other n=57 [core binding factor (n=3), cytogenetically normal AML (n=37), various aberrations (n=18)]. FLT3-ITD was present in 18 (22%) of 82 analyzed patients. Response to GO-A-HAM was as follows: CR, n=28 (30%); CRi, n=19 (20%); PR, n=11 (12%); refractory disease (RD), n= 34 (36%); and ED/HD, n=2 (2%). In a logistic regression analysis for achievement of CR, the only significant variable was adverse cytogenetics (OR 0.34, p=0.02). The rate of severe liver toxicity was 0%, the incidence of neutropenic fever was 52%, platelet and neutrophil recovery times from start of treatment were 21 and 22 days, respectively. Following GO-A-HAM, allogeneic SCT was actually performed in 60 patients (64%): matched related (n=14) or unrelated donor (n=42); haploidentical related donor, n=4. All SCT were performed within 3 months after GO-A-HAM, intermediate/severe VOD developed in 5 patients after SCT (9%, 95%-confidence interval (CI) 4–19%), mild VOD in 3 patients. Survival analyses revealed that patients with adverse cytogenetics and/or FLT3-ITD (n=45) had a significantly (p=0.001) inferior overall survival after one year of 38% compared to all other patients (n=39) of 81%. The proportions of patients receiving an allogeneic SCT were similar in both groups (68% and 66%, respectively). Conclusions: The GO-A-HAM regimen is feasible and effective as salvage therapy. However, cytogenetics still remains the most significant variable for achievement of response. Allogeneic SCT after GO-A-HAM was not associated with an increased VOD-rate.

Description: Background: Nucleophosmin (NPM1mut) mutations represent one of the most common gene mutations in acute myeloid leukaemia (AML) and can be used for monitoring minimal residual disease (MRD). In a former study, we could define clinical relevant check-points and a cut-off value to identify patients (pts) at high risk of relapse. Aims: To confirm our previous results on the clinical relevance of NPM1mut transcript levels (TL) in an extended cohort of younger AML pts (18 to 60 years) harbouring NPM1mut type A, B, C, D, JT, 4, QM, NM or KM, and to assess the impact of concurrent FLT3 internal tandem duplications (ITD) and DNMT3A (DNMT3Amut) mutations on NPM1mut TL kinetics. Methods: All pts were enrolled in one of four AMLSG [AMLHD98A (n=46; NCT00146120); AMLSG 07-04 (n=199; NCT00151242); AMLSG 09-09 (n=179; NCT00893399); AMLSG 16-10 (n=75; NCT01477606)] treatment trials. Treatment comprised double induction therapy (DI) with ICE (idarubicin, cytarabine, etoposide) with or without ATRA or gemtuzumab ozogamicin, or 1 cycle of daunorubicin and cytarabine followed by 1 to 4 cycles of high-dose cytarabine (n=292), autologous (n=19) or allogeneic stem cell transplantation (n=141). NPM1mut TL (ratio of NPM1mut/ABL1 transcripts x 104) were determined by RQ-PCR using TaqMan technology; the sensitivity of the assays was 10-5 to 10-6. DNMT3A and FLT3 -ITD (FLT3 -ITDmut) mutation status was assessed by standard PCR-based methods. Results: A total of 2835 samples from 499 NPM1mut pts were analysed at diagnosis (n=439), after each treatment cycle (n=1394) and during follow-up (FU) (n=1002). Peripheral blood (PB) samples were only included in the advanced FU period (defined as at least 12 months after completion of therapy). NPM1mut TL at diagnosis varied between 7.03 x103 and 2.38 x 107 (median 5.37 x 105). Pretreatment NPM1mut TL were not associated with clinical characteristics (e.g., age, WBC, BM blasts, FLT3 -ITDmut, DNMT3Amut) with the exception of LDH level (p=0.006) and did not impact event-free survival (EFS), relapse-free (RFS) and overall survival (OS). NPM1mut TL as log 10 transformed continuous variable at different time points during therapy were significantly associated with shorter remission duration (RD) and shorter OS. After DI therapy, the cumulative incidence of relapse (CIR) at 4 years was 10% for RQ-PCR-negative pts (n=41) versus 45% for RQ-PCR-positive pts (n=226) (p

Description: Background: The DNA methyltransferase 3A (DNMT3A) is one of the most frequent mutated genes in AML with a hot spot mutation at codon R882 in 80% of the DNMT3Amut cases. In most of the studies DNMT3Amut predicts for poor overall (OS) and relapse-free survival (RFS). Recently, DNMT3Amut have been associated with age-related clonal hematopoiesis, and they have been identified in early preleukemic stem cells. These findings suggest that DNMT3Amut represents an early event in leukemogenesis and may be part of the leukemia founder clone in most AMLs harboring a DNMT3Amut. We thought to address the question whether MRD monitoring in DNMT3Amut patients (pts) can be used for prognostic classification and risk stratification in these pts. Aims: We monitored MRD for the most common DNMT3Amut (DNMT3Amut -R882H, n=126 and -R882C, n=55) in a large cohort of adult AML pts entered on three AMLSG treatment trials [AML HD98A (n=14; NCT00146120), AMLSG 07-04 (n=86; NCT00151242), AMLSG 09-09 (n=81; NCT00893399)]. Methods: DNMT3Amut MRD monitoring was performed using a cDNA-based RQ-PCR-assay by TaqMan technology with a sensitivity between 10-3 and 10-4. MRD levels are reported as normalized values of DNMT3Amut transcripts per 104ABL1 transcripts (DNMT3Amut/104ABL1). Results: In total, 1,494 samples [bone marrow (BM), n=798; peripheral blood (PB), n=696] from 181 DNMT3Amut pts were analysed [diagnosis, n=287; during therapy, n=840; follow-up, n=367]. Median age of the patients was 50 years (range, 22 to 78); median BM DNMT3Amut transcript level (TL) at the time of diagnosis was 12690 (range, 1396-54280). There was no significant association of TL with presenting clinical characteristics, such as age, white blood cell count, platelet count, BM and PB blasts, lactate dehydrogenase, or with mutations in NPM1, FLT3 [ITD and TKD], CEBPA and cytogenetics. DNMT3Amut TL as log 10 transformed continuous variable and stratified by study did not impact OS (p=0.29), RFS (p=0.17) and EFS (p=0.28). Comparing TL after double induction (DI) did not show a significant difference between 13 patients without complete remission (CR) and 117 in CR (12983 and 12595, respectively; p=0.52). In Cox regression analyses, BM DNMT3Amut TL as log 10 transformed continuous variable during therapy did not impact the clinical endpoints death and relapse. In general, DNMT3Amut TL during therapy (after induction I, induction II, consolidation I and II) were significantly higher in BM than in PB (p=0.01; p=0.05; p=0.004; p=0.008, respectively). We observed the greatest TL reduction (one log) after induction I, whereas subsequent cycles of therapy did not significantly influence TL. To evaluate the impact of DNMT3Amut MRD monitoring with regard to the clinical endpoints OS, cumulative incidence of relapse (CIR) and remission duration (RD) after DI and after end of therapy (ET) we used different statistical approaches; all survival analyses were stratified by study. After DI and ET, only 8/90 and 4/88 BM samples became MRD negative. At these two time-points MRD positivity did not significantly impact OS (p=0.99; p=0.74), CIR (p=0.73; p=0.15) and RD (p=0.83; p=0.16). Next, we investigated the MRD DNMT3Amut log10-reduction (compared to levels at diagnosis) after DI and ET using the median as a cut-off. Again, we could not detect a significant correlation for pts with a higher TL reduction compared with pts with a lower TL reduction for OS and RD after DI and ET (p=0.83; p=0.30; p=0.04; p=0.21, respectively). Lastly, we evaluated the BM DNMT3Amut TL as 4 increasing equally sized intervals according to the quartiles of the distribution. There was no prognostic impact after DI on OS and RD (p=0.53; p=0.89) and ET (p=0.76; p=0.53). When combining PB and BM samples for the analyses we could not find significant changes in the results. Conclusion: In our study most pts had persistent DNMT3Amut TL with only a minority achieving MRD negativity, a finding that supports the presence of persistent clonal hematopoiesis in hematologic remission. Using different explorative approaches, DNMT3Amut TL did not impact clinical outcome neither during therapy nor during follow-up. Disclosures Horst: Gilead: Honoraria, Research Funding; Pfizer: Research Funding; MSD: Research Funding; Boehringer Ingleheim: Research Funding; Amgen: Honoraria, Research Funding. Schlenk:Arog: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Teva: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 2724 Background: The NHL 1 study, a prospective, multicenter, randomized, phase 3 study which compared B-R and CHOP-R as first-line treatment in indolent lymphomas and mantle cell lymphoma (MCL), demonstrated a significant benefit in progression-free survival (PFS) as well as improved tolerability for B-R compared with CHOP-R. Here we present an analysis of the impact of response quality on outcome. Methods: 514 patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. Results: The overall response rate in the 514 pts (261 B-R; 253 CHOP-R) was 92.7% and 91.3% in the B-R and CHOP-R arms, respectively (as presented at the last ASCO meeting, J Clin Oncol 30, 2012 (suppl; abstr 3). A complete response (CR) was observed in 39.8% in the B-R arm and in 30% in the CHOP-R arm (p=0.021). The achievement of CR was associated with a significantly prolonged PFS and overall survival (OS) (Table 1). Analysis by treatment arm revealed a trend for superior PFS and a significantly improved OS for patients achieving CR following treatment with B-R. In the CHOP-R arm, patients in CR had a significantly superior PFS compared to those in PR with a trend to superior OS. Regardless of the quality of response, PFS was superior with B-R versus CHOP-R: For patients in CR, the median PFS was not reached with B-R, whereas for CHOP-R it was 53.7 months (p=0.0204). In patients achieving PR, treatment with B-R resulted in a median PFS of 57.2 months, and this was 30.9 months with CHOP-R (p=0.0002). We noted a statistically significant difference in CR rates between male (n=272, median age 63 years) and female (n=242, median age 64 years) patients. The CR rate was 28.6% in male patients and 42.1% in female patients (p=0.0016). Female patients had a longer median PFS (51.4 months) compared to male patients (38.6 months), however, this difference was not statistically significant (p=0.0866). Conclusions: Patients in CR following first-line treatment in our study had a significantly longer PFS and OS compared to those achieving a PR. Therefore, our results strongly suggest an association between quality of response and outcome. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Relapsed/refractory (r/r) B-precursor ALL in adults has an unfavorable prognosis with a median overall survival of 4–8 months and a 5-year survival of

Description: Background: Measurable residual disease (MRD), as determined by quantitation of Nucleophosmin 1-mutated (NPM1mut) transcript levels (TL), provides significant prognostic information independent of other risk factors in patients (pts) with acute myeloid leukemia (AML). This is also addressed by the 2017 European LeukemiaNet (ELN) risk stratification system, which recommends taking into account results from MRD monitoring when selecting the appropriate post-remission therapy. Furthermore, MRD monitoring provides a powerful tool to evaluate treatment effects within clinical trials investigating novel therapies. Aims: To determine the impact of the anti-CD33 immunotoxin Gemtuzumab-Ozogamicin (GO) on kinetics of NPM1mut TL in pts with newly diagnosed NPM1mut AML [18 to 82 years (yrs), median age 58 yrs] enrolled in our randomized Phase III AMLSG 09-09 study (NCT00893399). In this study GO was randomized (1:1) to standard chemotherapy plus ATRA. Patients and Methods: In total, 588 evaluable pts were enrolled in the clinical AMLSG 09-09 study. Standard treatment comprised two cycles of induction therapy with A-ICE (ATRA, idarubicin, cytarabine, etoposide; arm A) followed by three consolidation cycles of high-dose cytarabine (n=371, 63%) or allogeneic hematopoietic cell transplantation (n=42, 8%). In the investigational arm (arm B), GO (3 mg/m²) was given at d1 of each induction and in the first consolidation cycle. 296 pts were randomized to arm A and 292 pts to arm B. For this correlative study, outcome analysis was restricted to the clinical endpoint cumulative incidence of relapse (CIR) due to study protocol requirements allowing overall survival analysis to be performed only two years after the last pt had been enrolled. MRD monitoring was performed in a total 503 pts for whom at least one bone marrow (BM) sample was available using RQ-PCR technique; the median follow-up (FU) of the 503 pts was 2.8 yrs. NPM1mut TL (ratio of NPM1mut/ABL1 transcripts x 104) were determined by RQ-PCR (sensitivity 10-5 to 10-6). Results: In total, 3711 BM samples were analyzed (at diagnosis, n=415; during treatment, n=1765; during FU, n=1531). Both study arms were well balanced with regard to pts characteristics and pretreatment NPM1mut TL. First, we evaluated the impact of GO on kinetics of NPM1mut TL during treatment. After the first induction cycle, median NPM1mut TL were significantly lower in the investigational arm (p=.001) and this was true for all subsequent treatment cycles [after induction II (p=.008), consolidation I (p

Description: Background: Mutations of the NPM1 gene are one of the most frequent genetic aberrations in adult AML. AML with mutated NPM1 is categorized as a disease entity according the WHO-2016 classification and clinically associated with female sex, high white blood cells at diagnosis, normal karyotype and high CD33 antigen expression. We recently showed that patients with NPM1-mutated AML benefit from all-trans retinoic acid (ATRA) as adjunct to intensive induction therapy (Ann Hematol. 2016; 95:1931-1942; Haematologica. 2009;94:54-60). Based on the regular high CD33 expression in AML with mutated NPM1 we hypothesized that gemtuzumab ozogamicin (GO) added to intensive therapy with ATRA may further improve clinical outcome in AML with mutated NPM1. Aim: To evaluate GO in combination with intensive induction and consolidation therapy and ATRA in NPM1 mutated AML within the randomized AMLSG 09-09 trial (NCT00893399) Methods: Between May 2010 and September 2017, patients ≥18 years of age and considered eligible for intensive therapy were randomized up-front for open-label treatment with GO. Induction therapy consisted of two cycles of A-ICE (idarubicin 12mg/m² iv, day 1,3,5 [in induction II and for patients 〉60 years reduced to d 1, 3]; cytarabine 100mg/m² continuous iv, day 1 to 7; etoposide 100mg/m² iv, day 1-3 [in induction II and for patients 〉60 years reduced to d 1, 3]; ATRA 45 mg/m²/day po on days 6-8 and 15mg/m² days 9-21, +/- GO 3mg/m² iv day 1). Consolidation therapy consisted of 3 cycles of high-dose cytarabine (HiDAC; 3g/m² [reduced to 1g/m² in patients 〉60 years] bid, days 1-3; Pegfilgrastim 6mg sc, day 10; ATRA 15 mg/m²/day po, days 4-21; +/- GO 3mg/m² on day 1 [first consolidation only]). The primary endpoints of the study were event-free survival (EFS) as early endpoint tested 6 months and overall survival (OS) tested 4 years after study completion with sequential testing according the fallback procedure described by Wiens (Statistics 2003;2:211-215). This report focusses on the early EFS endpoint. Further secondary endpoints were response to induction therapy, cumulative incidence of relapse (CIR) and cumulative incidence of death (CID). Results: In total 588 patients were evaluable for analysis (n=296, standard-arm; n=292 GO-arm). Median age was 58.7 years (range, 18.4-82.3 years), ECOG performance status was 0 in 34.1% and 1 in 55.1%, and FLT3-ITD was present in 16.8% of the patients, with baseline characteristics well balanced between the two arms. After first induction therapy death rates were significantly higher in the GO-arm (7.5%) (p=0.02) compared to the standard-arm (3.4%); in both study-arms causes of death were mainly infections. Following induction therapy complete remission (CR) and CR with incomplete count recovery (CRi) were 88.5% and 85.3% (p=0.28), refractory disease (RD) 6.1% and 5.1% (p=0.72), death 5.4% and 9.6% (p=0.06) in the standard- and GO-arm, respectively. Due to prolonged thrombocytopenia after second induction therapy in the GO-arm, the protocol was amended in that GO was omitted in second induction and first consolidation cycles, if prolonged cytopenias were observed during first induction therapy. The study treatment was completed in 197 and 171 patients (p=0.11), allogeneic hematopoietic cell transplantation in first CR was performed in 18 and 21 patients (p=0.51) in the standard- and GO-arm, respectively. Median follow-up was 2.6 years (95%-CI, 2.4-3.1 years). Two- and 4-year EFS were 53% (95%-CI, 48-60%) and 58% (95%-CI, 52%-64%), and 44% (95%-CI, 38-52%) and 52% (95%-CI, 46%-59%) in the standard- and GO-arm, respectively. According to the pre-specified significance level of 0.025, EFS in the GO-arm was not different to that in the standard-arm (p=0.21). In patients achieving CR/CRi after induction therapy, CIR was significantly reduced in the GO-arm compared to the standard-arm (p=0.018), whereas no difference in CID was noted between both arms (p=0.89). Conclusion: The addition of GO to intensive induction therapy with ICE plus ATRA was associated with a higher death rate. In patients achieving a CR/CRi after induction therapy significantly less relapses occurred in the GO- compared to the standard-arm. Disclosures Schlenk: Pfizer: Research Funding, Speakers Bureau. Paschka:Astex: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees, Travel support; Otsuka: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Other: Travel support, Speakers Bureau; Jazz: Speakers Bureau; Amgen: Other: Travel support; Janssen: Other: Travel support; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Travel support. Fiedler:Amgen: Other: support for meetíng attendance; Gilead: Other: support for meeting attendance; Pfizer: Research Funding; Amgen: Research Funding; Amgen: Patents & Royalties; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; ARIAD/Incyte: Membership on an entity's Board of Directors or advisory committees, support for meeting attendance; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSO: Other: support for meeting attendance; Teva: Other: support for meeting attendance; JAZZ Pharmaceuticals: Other: support for meeting attendance; Daiichi Sankyo: Other: support for meeting attendance. Lübbert:Cheplapharm: Other: Study drug; Celgene: Other: Travel Support; Janssen: Honoraria, Research Funding; TEVA: Other: Study drug. Götze:Novartis: Honoraria; Takeda: Honoraria, Other: Travel aid ASH 2017; JAZZ Pharmaceuticals: Honoraria; Celgene: Honoraria, Research Funding. Schleicher:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Investigator; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Ipsen: Membership on an entity's Board of Directors or advisory committees; Eissai: Other: Investigator; Astra Zeneca: Other: Investigator; Pfizer: Speakers Bureau; Janssen: Speakers Bureau; Celgene: Speakers Bureau. Greil:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Honoraria, Research Funding; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sandoz: Honoraria, Research Funding; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Heuser:Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; BergenBio: Research Funding; Karyopharm: Research Funding; Daiichi Sankyo: Research Funding; Sunesis: Research Funding; Tetralogic: Research Funding; Bayer Pharma AG: Consultancy, Research Funding; StemLine Therapeutics: Consultancy; Janssen: Consultancy. Ganser:Novartis: Membership on an entity's Board of Directors or advisory committees. Döhner:Agios: Consultancy, Honoraria; Pfizer: Research Funding; Sunesis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Astex Pharmaceuticals: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; AROG Pharmaceuticals: Research Funding; Agios: Consultancy, Honoraria; Bristol Myers Squibb: Research Funding; Celator: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Astex Pharmaceuticals: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AROG Pharmaceuticals: Research Funding; Jazz: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Sunesis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Celator: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding.

Description: Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell–engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome–negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The original study and this follow-up study are registered at www.clinicaltrials.gov as NCT00198991 and NCT00198978, respectively.