ALBERT

Description: Abstract 3996 Background: AZA significantly improves OS in higher-risk MDS (including RAEB-t/AML) compared to conventional treatments (AZA 001 trial, Lancet Onc, 2009), but prognostic factors of response and OS to AZA remain largely unknown. We designed a prognostic score for OS in a cohort of AZA treated higher-risk MDS in a patient-named compassionate program (French ATU), and validated it in patients from the AZA 001 trial. Methods: Between Sept 2004 and Jan 2009, prior to AZA approval in Europe, IPSS int-2/high risk MDS (including RAEB-t) not previously treated with intensive chemotherapy (IC), allo SCT, or a hypomethylating agent were included in a compassionate program (ATU), and received AZA (planned schedule 75 mg/m2/d ×7 d every 28 d for ≥4 cycles). Independent prognostic factors of OS were individualized in a Cox model. A prognostic score was then developed based on those factors. After validation of the score as a continuous variable, pts were grouped in three distinct risk categories. We subsequently tried to validate this score in the 175 higher risk MDS pts treated with AZA at the same schedule in AZA 001 trial (4 of the 179 pts randomized to AZA in that trial did not start AZA). Results: The ATU cohort included 282 pts with de novo (74%) or therapy related (t) (26%) higher-risk MDS (IPSS int-2 in 54% high in 43%, at least int-2 in 2%). ECOG PS ≥2, RBC transfusion dependence ≥4 units/8 weeks and circulating blasts were present in 21%, 46% and 46% of pts respectively (resp). Cytogenetic risk was good, int, and poor in 31%, 17% and 47% (unknown in 5%). 10% pts had previously been treated with LD araC for their MDS. Multivariate analysis of survival retained PS ≥2 (HR= 2.0 [95% CI: 1.4–2.9]), RBC transfusion dependence ≥4 units/8 weeks (HR=1.9 [1.4-2.6]), presence of circulating blasts (HR=2.0 [1.5-2.7]), and IPSS cytogenetic risk (intermediate: HR=1.4 [0.8-2.3], poor: HR=3.0 [2.0-4.3]) as independent prognostic factors (all p

Description: Abstract 843 Background: AZA prolongs survival in higher-risk MDS including patients (pts) with 20-29 % marrow blasts, now considered WHO-AML ( Lancet Onc, 2009). However, no large AML cohorts (especially with '30% marrow blasts) treated upfront with AZA have been reported. Methods: An AZA compassionate program (ATU) was initiated in France in Dec 2004 for higher risk MDS, and AML considered not candidates or refractory to intensive chemotherapy (IC). We retrospectively analyzed WHO AML pts having received at least 1 cycle of AZA in the 42 centers with complete pt reporting, excluding those previously treated by IC, allo SCT, low dose AraC or a hypomethylating agent. Results: 138 pts were included between Dec 2004 and Dec 2008; M/F: 86/52; median age 73 years (y) (range 31-87), 117 pts (85%) were 〉 65 y and 54 (40%) 〉75y. 65 pts (47%) had prior WHO MDS and 30 pts (22%) therapy related (tAML). 44 pts (32%) had 20-29% marrow blasts. Median WBC was 3.0 G/L [0.8-111.5]. Karyotype (MRC classification), was intermediate (int) in 60 pts,( including 38 normal (NK), and 7 isolated +8 ) adverse in 67 pts (including 42 -7/ del7q, 41 del5q/-5, 45 complex karyotype, two 3q26) and failed in 11 pts. With a median follow-up of 11.3 months, pts received a median of 4.5 AZA cycles (range 1-26). Treatment was according to FDA-EMEA approved schedule for MDS in 95 pts (69%) and a less intensive schedule (5d/4w, or 10 G/L (32 pts in our cohort) carried poorer prognosis ( 1 y OS of 27% vs 44% ,p=0.01); NK had better OS (1-y OS: 66%) than adverse cytogenetics (1-y OS: 30%, p=0.01) but also other “intermediate-risk” abnormalities (1-y OS: 30%, p=0.03). Marrow blast % did not influence OS and survival, whatever the cut off chosen. In particular, pts with 20-29 % marrow blasts had 22% AML response and 1 y OS of 50%, compared to 21% and 1 y OS of 35%, respectively, in pts with 〉30% marrow blasts (p=NS and NS, respectively). Prior MDS also had no influence on survival. Overall, 33 pts required hospitalization during treatment, mainly for neutropenic fever. A landmark analysis at the time of evaluation showed that achievement of CR, CRi or PR was associated with improved OS (1y-OS 55% vs 31%,p=0.007). In pts with no AML-IWG response, however, achievement of HI also predicted better survival: 1 y-OS 55% vs 19 %, p=0.02. In the 54 pts older than 75 y (ie pts generally considered unfit for IC), 12 (22%) had AML response including CR in 9 (17%) and 3 PR (5%). 1y-OS was 41 % vs 38% for younger pts (p=NS). Hospitalisation was needed in 31% of them vs 32% in younger pts (p=NS). Conclusion: In this untreated cohort of generally older AML pts considered non candidates for intensive chemotherapy, response rate was 21% and 1 y OS 40%. Higher WBC counts and adverse karyotype were associated with poorer OS, but marrow blast %, whatever the threshold chosen, had no influence on outcome. Age above 75 y was associated with similar response and 1y OS. Finally, pts without AML IWG responses but with improved cytopenias also appeared to have improved survival. Disclosures: Off Label Use: Azacytidine is approved by FDA and EMEA in the treatment of high risk MDS and AML up to 30% of bone marrow blast.. Fenaux:CELGENE: Research Funding; AMGEN: Research Funding.

Description: PNH is a rare acquired disorder. We aimed to analyze a large cohort of patients on the long term to better determine prognostic factors. We already reported the analysis on 220 patients in 1996 (Socié et al, Lancet). Data were updated and we collected additional data on 247 patients (total of 467 patients, 252 female), diagnosed from 1950 to 2005 from 58 centers. The date of diagnosis was based on flow cytometry analysis if there was no prior positive Ham’s test. The age at diagnosis was 34 years (±17.3). The median follow-up time was 6.8 years (±0.5). Kaplan-Meier 10-year survival estimate was 76.3% (± 2.6). Sixty seven (14.6%) patients developed pancytopenia during follow-up [10-year cumulative incidence (CIn) rate of 18.3% (14% – 22%)]. Deep-vein thrombosis occurred in 108 patients (23.5%) [10-year CIn 28% (23% – 33.1%)]. Nineteen patients developed myelodysplastic syndrome (MDS) [10-year CIn 4.6% (2.4% to 6.8%)]. Eight patients developed acute leukemia [10-year CIn 2.3% (0.4% to 3.9%)]. The following factors were related to poor survival: Older age at diagnosis; age between 40 and 55 years [relative risk RR=2.4 (95% CI 1.4–4.1); p value

Description: Abstract 1713 Abstract Title: Is azacitidine (AZA) really effective in higher risk MDS patients with chromosome 7 abnormalities (Abn 7)? Results of a retrospective study from the GFM and GESMD registries. Background: Cytogenetic alterations are the most discriminative prognostic variables in MDS, complex karyotype and abnormalities of chromosome 7 (Abn 7) having the poorest outcome. However, prognosis of isolated 7q- and to a lesser extent isolated −7 appears to be less severe than that of complex karyotypes at least in patients not receiving drugs with a potential effect on survival (Schanz et al, JCO, 2012, Cordoba et al, Cancer, 2012). It has been suggested in relatively small patients series that Abn 7 may be associated with relatively favorable response to AZA in MDS. We analyzed the outcome of a large series of higher risk MDS with Abn 7 treated with AZA. Methods: Between 2005 and 2011, higher risk MDS pts were treated with AZA (75 mg/m2/d during 7 or less often 5 days / 4 weeks, scheduled for at least 6 cycles), in compassionate programs (prior to AZA approval by EU) or within AZA label (since 2008) and included in the French and Spanish MDS registries. We retrospectively analyzed, in those series, the outcome of pts with Abn 7. Results: 123 pts with Abn 7 having received at least one cycle of AZA, including 82 (66%) de novo MDS and 69 males (55%), with a median age of 70y (range 33–89) were analyzed. At diagnosis, according to WHO 2008, 52% pts (n=65) had RAEB2, 16% (n=20) had RAEB1 and 10% (n=13) had AML with 20–30% marrow blasts (RAEB-T according to FAB). IPSS was high in 51% (n=64), int-2 in 43% (n=55), and not available (but at least int-2) in the remaining 25 pts. Karyotype distribution was: monosomy 7 (−7) (isolated or with 1 other abnormality, non complex −7) in 33 patients (27%), 7q- (isolated or with 1 other abnormality, non complex 7q-) in 19 patients (16%), del(7p) (isolated or with 1 other abn) in 1 patient (1%), and 69 patients (56%) had complex karyotype (〉= 3 abn) with −7 or 7q-. Among 106 patients with this information available, 74% (n=78) were RBC and/or PLT transfusion dependent (TD). 86% (n=108) of the patients received the conventional 7 day schedule of AZA, the remaining 14% receiving reduced daily dosing or 5 day cycles. The median number of cycles administered was 5 (1–32). Among 110 patients with available information the overall response rate (IWG 2006 criteria) was 32% (35/110), including 12% CR and 20% SD with HI. Among non responders, 12% died prior to evaluation, 33% were in SD and 23% progressed. Among transfusion dependent patients, 16% became RBC transfusion independent (12 of 73 TD patients with available information). The overall response rate was 30% in pts with complex karyotype with −7 or 7q-, 33% in pts with non complex −7 and 31% in pts with non complex 7q- (p=0.1 for complex vs non complex Abn 7). At the time of last follow up, 66 patients (53%) had relapsed or progressed and 102 (83%) had died. Median event free survival(considering death, relapse or progression as events ) at 1 and 2 years was 32 and 8%, respectively. Median OS at 1 and 2 years was 40%, and 18%, respectively. OS was better for patients with response after 4–6 cycles (OS at 1 year 64%) when compared with SD (1y OS 47%) or progression (1y OS 12%), p

Description: Introduction: The autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells demonstrated significant clinical benefits and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with an ORR of 52-83% and CR of 40-58% in the 3 pivotal clinical trials (ZUMA-1, TRANSCEND-NHL-001, JULIET), leading to a rapid approval in third line R/R DLBCL in Europe and in USA. The CD19 CAR T-cells Axicabtagene and Tisagenlecleucel have been approved in France since June 2018 for patients with DLBCL, primary mediastinal B-cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after 〉 2 systemic therapy lines. However, all patients are not deemed eligible for such therapy. Here we describe the characteristics of the non-eligible patients and the causes of non-eligibility for CD19 CAR T-cells at our center. Methods: We performed a retrospective analysis of all patients for whom our center was contacted for potential eligibility to CD19 CAR T-cells. Upon each request, a screening form was completed by the referring hospital to validate the indication (DLBCL, PMBL or tFL; recurrent or refractory to 〉 2 systemic therapy lines) and the absence of contra-indications (CNS involvement (MRI mandatory), active infection). The patient was then evaluated in our hospital to check the predetermined eligibility criteria: age, comorbidities, LVEF 〉 45%, no pericarditis or cardiogram abnormality, creatinine clearance 〉 60 mL/min, ALT/AST 〈 2.5 N, total bilirubin 〈 1.5 mg/dL, no pleural effusion, SpO2 〉 92% without oxygen, lymphocytes 〉 100/µL, no rapid progressive disease (compressive mass, PS 〉 2 or rapid increase of LDH), or no active neurological/auto-immune disease. In case of severe comorbidities or age〉 70, patient's frailty index was assessed by an ICU physician. Eligibility was then finally validated by our local board through a careful case-by-case analysis. Results: Between June 2018 and July 31, 2019, 221 requests were analyzed. Evaluation is still ongoing for 6 patients (3%). 80/215 patients (37%) were deemed eligible for CAR T-cells, 58 patients (27%) were excluded before any visit at the expert hospital because of histology other than DLBCL, PMBL and tFL (n=30: non-transformed FL 9, transformed SLL/CLL 7, transformed Waldenström 3, transformed MZL 3, MZL 2, primary CNS lymphoma 2, SLL/CLL 1, HL 1, lymphoblastic lymphoma 1, CD19- 1), 〈 2 previous lines (n=7), CNS involvement (n=7), administrative reason (n=14). The remaining 77 patients (36%) were deemed non-eligible for CAR T-cells after the first visit. Median age was 59 years (range 18-86, 41% ≥ 65 years), 68% were male. There were 62, 4 and 2 patients with DLBCL, PMBL and tFL, respectively. Median number of prior lines was 3 (range 2-11, 43% 〉 3 lines), 86% of patients presented with a primary refractory disease. Nine patients were with a refractory disease despite stem cell transplantation (SCT, 5 autologous, 3 allogeneic and 1 both). Considering these 77 patients, 12 (16%) had 2 concomitant causes of non-eligibility. Overall, the two main causes of non-eligibility were rapid disease progression (n=49) and major frailty (n=23), including 10 patients with 11 severe organ dysfunctions [5 cardiac, 3 kidney, 1 liver, 1 respiratory and 1 heavy engine handicap]. Replicative viral infections (n=4) constituted also an important cause of frailty: HIV (1), HBV (2), HBV + HCV (1). Two patients had a solid organ transplantation requiring immunosuppressive drugs. Advanced neurological diseases (n=4) included: extrapyramidal syndrome (3), advanced multiple sclerosis (1). Active autoimmune diseases were a cause of frailty for 2 patients: thyroiditis (1), periodic fever (1). In one patient, the screening evaluation showed a concomitant malignancy. Other causes of non-eligibility were found in 17 patients: complete remission after the salvage therapy (n=7), age 〉 80 (n=4), severe thrombocytopenia 〈 20 G/L (n=2), no slot available (n=1), patient refusal (n=3). Outcomes of the non-eligible patients (alternative treatments, survival) will be presented at the meeting. Conclusion: In this pioneering experience, 37% of patients in whom a CAR T-cell request is made are ultimately deemed eligible for the therapy. Other patients are either rapidly excluded based on lack of CAR T-cells indications (27%), or deemed non-eligible because of failure to control the disease / major frailty (36%). Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: 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. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Gyan:Pfizer: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Novartis: Honoraria.

Description: Transformation of Philadelphia (Ph)–negative myeloproliferative neoplasms (MPNs) to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is associated with poor response to chemotherapy and short survival. Fifty-four patients with Ph-negative MPN (including 21 essential thrombocythemia [ET], 21 polycythemia vera [PV], 7 primary myelofibrosis, and 5 unclassified MPN) who had progressed to AML (n = 26) or MDS (n = 28) were treated with azacitidine in a patient-named program. Overall response rate was 52% (24% complete response [CR], 11% partial response [PR], 8% marrow CR or CR with incomplete recovery of cytopenias, 9% hematologic improvement) and median response duration was 9 months. Prognostic factors were for overall response the underlying MPN (71% vs 33% responses in ET and PV, respectively; P = .016); prognostic factors for CR achievement were the underlying MPN (14% CR for PV vs 43% for ET; P = .040) and World Health Organization classification at transformation (36% vs 12% CR in MDS and AML, respectively, P = .038). Recurrence of chronic phase features of the initial MPN was observed in 39% of the responders. Median overall survival was 11 months. Azacitidine gives encouraging results in Ph-negative MPN having progressed to AML or MDS, but response duration is short, and consolidation treatments have to be evaluated.

Description: Dasatinib (Sprycel®, Bristol-Myers Squibb) is a potent multi-targeted kinase inhibitor (TKI) of BCR-ABL and SRC family kinases. Despite a 33% complete hematological response (CHR) rate in a Phase 2 study in patients with Philadelphia positive (Ph+) acute lymphoblastic leukaemia (ALL) intolerant or resistant to imatinib, the median duration of progression-free survival (PFS) was 3.3 months (Ottmann et al. Blood. 2007;110:2309-2315). Second-generation TKI may thus have a place in the management of these patients. As a European consensus has been reached by the EWALL to adopt a common first-line chemotherapeutic schedule for elderly patients (aged 55 years or more) with Ph-positive ALL, this schedule was used here to test the addition of dasatinib. After a prephase with dexamethasone 10 mg/m2 d-7 to d-3, the induction phase consisted in IV injections of vincristine 1 mg combined with 2 days of dexamethasone 40 mg PO repeated weekly for 4 weeks followed by consolidation cycles including methotrexate 1000 mg/m2 IV d1 (500 mg/m2 over 70y) and asparaginase 10,000 UI/m2 IM d2 (5,000 UI/m2 over 70y) for cycles 1, 3 and 5 alternating with cytarabine 1,000 mg/m2/12h IV d1, d3, d5 (500 mg/m2 over 70y) for cycles 2, 4 and 6. Maintenance phase consisted in 6-MP 60 mg/m2/d and methotrexate 25 mg/m2/week orally 1 month every other month and dexamethasone/vincristine in 2 months intervals during the first year and in 3 months intervals during the second year. Dasatinib (provided by Bristol-Myers Squibb) was administered at 140 mg per day (QD) during the induction period in combination with chemotherapy and at 100 mg/d sequentially with the chemotherapy courses during consolidation and maintenance. BCRABL analysis was performed according to the European Leukemia Net recommendations in two centralized laboratories. A total of 22 patients were included from August 2007 to June 2008. Median age was 71 years (range, 61 to 83), sex ratio (M/F) was 0,46, and median follow-up was 5.8 months. The Ph+ chromosome was associated with complex abnormalities in 58% of cases and 84% of the patients were m-BCR. The CHR rate was 95.2% (20 out of 21 evaluable patients). The only case of induction failure was due to death. The rate of complete molecular remission (CMR) after induction was 33% in blood and 28% in bone marrow and MRD level continued to decrease with time. Only one relapse was observed before the consolidation phase. No other relapse occurred for the 13 patients in CHR still in study after a median follow-up of 3.6 months. One patient died during induction from invasive aspergillosis, 3 deaths occurred in CR, 2 before consolidation due to pulmonary embolism and physical deterioration, and one during maintenance from pneumonia. Serious adverse events (SAEs) were reported in 7 out of 22 patients during induction (31.8%) and in 2 out of 13 patients during maintenance and consolidation (15.3%). SAEs consisted in renal failure (n=3, 2 from acute lysis syndrome and 1 tubular necrosis), invasive aspergillosis (n=1), pulmonary embolism (n=2), pneumonia (n=1), atrial arythmia (n=2), pleural effusion (n=1), microangiopathy (n=1), cytolytic hepatitis (n=1) and physical deterioration (n=1). Eight patients discontinued the study after induction (35%). Primary reasons for discontinuation were SAEs (n=4), death (n=3) and relapse (n=1). The EWALL-PH-01 protocol is highly effective with a 95.2% RCH rate in elderly patients with Ph-positive ALL. Of importance, responses appeared to be durable and MRD level was decreasing over time. An expected 40% rate of SAEs was observed in this elderly population. Reduced doses of therapy are now applied for patients over 70y (20 mg for dexamethasone, 100 mg/d for dasatinib).

Description: Abstract 4003 Introduction: Azacytidine (AZA) has significantly improved the management and survival of patients (pts) treated for high risk myelodysplastic syndrome (MDS). However, 40 to 50% of patients will not achieve any kind of response and most responders relapse within 2 years (Fenaux Lancet Oncology 2009). Aternative strategies are so required for this population with primary or secondary failure of AZA. Vorinostat is a second generation histone deacetylase inhibitor with significant clinical activity in MDS and leukemia, although the response rate remains low (Garcia-Manero Blood 2008). Synergy of vorinostat with both conventional cytotoxic agents and targeted therapy has been demonstrated in vitro and in vivo (Esteller NEJM 2008). Methods: In this still ongoing study (clinicaltrials.gov NCT00776503), we combined low-dose cytarabine (10-20 mg/m2/day for 14 days sub-cutaneously) and escalating total doses of vorinostat. Two schedules of vorinostat, (400mg/day orally) beginning on day 1 (arm A) or on day 14 (arm B), were tested in 3 groups receiving escalating treatment duration (7days, 10 days and 14 days) following a classical 3+3 phase I schedule. 10 additional pts will be included at the recommended dose level of each cohort (arm A and B). Inclusion criteria were age 〉18, MDS or AML

Description: Abstract 172 Background. Dasatinib (Sprycel®) is a potent inhibitor of BCR-ABL and SRC family kinases. Based on the rapid and clinically meaningful activity observed when dasatinib was used as a single agent a consensus has been reached by the EWALL (European Working Group for Adult ALL) to conduct an international study evaluating the combination of dasatinib and low-intensity chemotherapy in patients with Ph+ ALL aged 55 years or more. Patients and Methods. After a prephase with dexamethasone 10 mg/m2 d-7 to d-3, dasatinib was administered at 140 mg QD (100 mg in patients over 70y) during the induction period in combination with IV injections of vincristine 1 mg and dexamethasone 40 mg 2 days (20 mg over 70y) repeated weekly for 4 weeks. Consolidation cycles consisted of dasatinib 100 mg/d administered sequentially with methotrexate 1000 mg/m2 IV d1 (500 mg/m2 over 70y) and L-asparaginase 10,000 UI/m2 IM d2 (5,000 UI/m2 over 70y) for cycles 1, 3 and 5 and cytarabine 1,000 mg/m2/12h IV d1, d3, d5 (500 mg/m2 over 70y) for cycles 2, 4 and 6. Maintenance phase consisted of dasatinib alternating with 6-MP and methotrexate orally every other month and dexamethasone/vincristine once every 2 months for up to 24 months. Patients were molecularly monitored by a central laboratory for BCR-ABL RTQ-PCR and T315I resistance mutation ASO RTQ-PCR. Results. Seventy one patients were included from August 2007 to study termination in May 2010. Median age was 69.1 years (range: 58–83). Median follow-up was 16.3 months. At diagnosis, the Ph chromosome was associated with other abnormalities (complex, -7, Ph duplication or others) in 64.5% of cases. The CR rate after induction was 90% and 55.7% of the patients achieved a BCR-ABL/ABL ratio ≤0.1% at the time of CR. Failure to achieve CR was mainly related to death (n=5.7%). Serious adverse events (SAEs) during induction were infections (11%), elevated transaminases (7%), hemorrhage (5.6%), renal failure due to tumor lysis syndrome (4.2%) and cardiovascular events (5.6%). Only 2 pleural effusions were observed. During consolidation and maintenance, most frequent SAEs were infections (33.3%). One pleural effusion was observed. Nineteen patients relapsed after a median response duration of 19.2 weeks and 12 of them died. Thirteen patients presented mutations in the BCR-ABL TK domain at relapse (12 T315I, 1 F317L), no mutation was detected in 3 patients and results are pending in 3 patients. T315I ASO RTQ-PCR analysis during follow-up was predictive for relapse. The rise of the T315I signal over 0.1% was always associated with relapse and occurred 1 to 3 months before relapse in 6 of the 12 T315I cases and concomitantly in the 6 remaining patients. Four patients received RIC allogenic stem cell transplantation and were censored at the time of SCT. Median RFS and OS were 22.1 and 27.1 months, respectively. Cytogenetics findings at diagnosis were good predictors for RFS: the median RFS for patients with isolated Ph was not reached while it was 19.2 months in patients with additional cytogenetic abnormalities (p=0.03)). Molecular BCR-ABL transcript level after induction had no effect on RFS. However, a BCR-ABL ratio ≤0.1% after induction and then confirmed during consolidation was significantly associated with a better RFS (5.1 months versus not reached, p=0.006). Conclusions. Dasatinib combined with low-intensity chemotherapy is highly effective in elderly patients with Ph-positive ALL with a 90% CR rate and a 22.1 months RFS. Cytogenetics at diagnosis is a strong predictive factor for RFS. Most relapses were associated with the T315I mutation. Serial monitoring for T315I allowed us to predict for hematological relapse and may offer an opportunity to adapt therapy before relapse. Disclosures: Rousselot: Bristol Myers Squibb: Research Funding. Off Label Use: Dasatinib as first line therapy in Ph ALL.

Description: Bortezomib has a well known efficacy in multiple myeloma, but effects on AML cells is only observed in vitro and remain to be clinically proved. In a 78 year-old patient, we diagnosed two concomitant aggressive hematological malignancies: IgA Kappa multiple myeloma and de novo FAB-M5 AML. The patient was consulting for bone pain and progressive bicytopenia. The bone marrow was infiltrated with 30% dystrophic plasmocytes and 35% myeloïd monoblastes with CD13+, CD33+ phenotype. A serum M component of 5 g/dl IgA kappa was present at diagnosis with mild acute renal failure, elevated beta2microglobulinemia and IPSS score of 2. The cytogenetic study revealed poor prognosis factors for both malignancies with a complex caryotype including chromosome 13 abnormalities and MLL rearrangement. Standard treatments to cure both diseases one after the other could not be a good option, due to the presence of these poor prognosis factors. Thus, we decided to treat the patient with Bortezomib, a proteasome inhibitor known to induce clinical response in multiple myeloma and apoptosis of leukemia cell lines in vitro. After two cycles of Bortezomib (1.3 mg/m2 day 1,4,8,11) combined with steroids (dexamethasone, 40 mg day 1–4), the patient obtained a near complete myeloma remission with normal electrophoresis, but also disappearance of circulating AML blast and a 70% reduction of medullary AML blasts. Low-dose cytarabine (15 mg twice the day for 10 days) was introduced after the fourth cycle of bortezomib because of persistent circulating AML blasts. Bortezomib was stopped after 5 cycles because of neurological adverse event. After 5 cycles of cytarabine, the patient reached complete cytogenetic remission of both diseases. The patient still remains in complete remission after 13 months of follow-up. We conclude that bortezomib had a partial efficacy on AML cells in vivo and could have synergized with cytarabine to reach and maintain complete remission of both poor prognosis AML and multiple in this patient.