Cycles Of Consolidation Therapy Research Articles

Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy in Patients with Unresectable Stage III Non-Small Cell Lung Cancer Receiving Concurrent Chemotherapy: A Multicenter, Randomized Phase 3 Trial

PurposeThe standard treatment schedule for unresectable stage III non–small-cell lung cancer (NSCLC) is chemotherapy with concurrent radiotherapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiotherapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiotherapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy. Methods and MaterialsIn this randomized multicentre non-blinded phase III clinical trial, eligible patients were randomized at a 1:1 ratio to either the Hypo-RT group, (60 Gy in 20 fractions) or to the Con-RT group (60 Gy in 30 fractions). All patients received two cycles of concurrent platinum-based chemotherapy plus two cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival (PFS) and treatment-related adverse events. ResultsA total of 146 patients were enrolled from July 27, 2018 to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and the Con-RT groups were 58.4% and 38.4%, respectively (P = 0.02). The median OS from randomization was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40–0.94; P = 0.02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the two groups. ConclusionsModerately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC while maintaining toxicity rates. TRIAL REGISTRATION Chinese Clinical Trial RegistryChiCTR1800017367

CD81 and Its Relationship to Treatment Response in Patients With Acute Myeloid Leukemia at a Hospital in Hanoi, Vietnam.

Acute myeloid leukemia (AML) has the proliferation of poorly differentiated immature myeloid cells. New studies on immune markers also consider them as one of the factors that affect the prognosis or the patient's ability to respond to drugs. Our study was designed to determine the rate of remission and mortality, and the ability to respond to drugs in newly diagnosed AML patients withpositive CD81. A total of 50 patients diagnosed with AML (excluding acute promyelocytic leukemia) underwent immunophenotyping analysis using flow cytometry. Following the initial diagnosis, the patients received induction therapy, followed by three cycles of consolidation therapy. The patients were then followed up for a period of six months. The treatment efficacy was assessed at two timepoints: on day 28 after the first chemotherapy course and on day 28 after the fourth chemotherapy course. Out of the 50 newly diagnosed AML patients, 40 (80%) were found to be CD81 positive. This CD81-positive group had a high mortality rate after the first course of chemotherapy (17.5%)and after the fourth course of chemotherapy(52.5%), while no patients died in the CD81-negative group. The CD81-positive group had a worse drug response rate with 22.5% and 18.2% in CD81 positive group versus 30% and 40% in the CD81-negative group achieving complete remission after the first course and fourth course, respectively. The CD81 immunological marker was found to be highly prevalent among AML patients in Vietnam. Overexpression of CD81 in patients with AML is associated with an unfavorable prognosis, characterized by higher mortality rates and poorer treatment response.

An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial)

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

Autologous hematopoietic stem cell transplantation followed by interleukin-2 for adult acute myeloid leukemia patients with favorable or intermediate risk after complete remission.

High-dose chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is generally the optimal option for patients with acute myeloid leukemia (AML). However, for favorable- and intermediate-risk patients, the regimen remains less understood due to graft versus host disease (GVHD) and increased non-relapsed mortality (NRM) caused by allo-HSCT. Additionally, the benefit of maintenance therapy has not yet been conclusively proven. Here, we conducted a retrospective study on the long-term outcome of AML patients with favorable or intermediate risk who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) followed by interleukin-2 (IL-2) subcutaneous injection as maintenance therapy. A total of 49 patients from 2007 to 2019 were included in our study. They all received a daunorubicin + cytarabine regimen as induction chemotherapy followed by four to six cycles of consolidation therapy with medium- or high-dose cytarabine. Once patients achieved complete remission (CR1), they started receiving auto-HSCT followed by IL-2 injections. The results showed that no patients stopped receiving IL-2 injections on account of adverse side effects, and the 5-year overall survival (OS) and leukemia-free survival (LFS) rates were 85.6 ± 5.0% and 78.5 ± 6.1%, respectively. The multivariate analysis also suggested that age, gender, initial white blood cell (WBC) count, AML subtype, cytogenetic risk, and conditioning regimen did not affect the prognosis. In conclusion, auto-HSCT followed by IL-2 injection is an effective treatment that can improve the prognosis of AML for patients with favorable or intermediate risk.

Updated Survival and Response Analyses from a Phase 1 Study of Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation

Updated Survival and Response Analyses from a Phase 1 Study of Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation

FLT3-Mutated Acute Myeloid Leukemia Using a Novel Regimen of Gemtuzumab Ozogamicin and Midostaurin in Combination with Standard Cytarabine and Daunorubicin Induction Therapy

FLT3-Mutated Acute Myeloid Leukemia Using a Novel Regimen of Gemtuzumab Ozogamicin and Midostaurin in Combination with Standard Cytarabine and Daunorubicin Induction Therapy

Two Cycles of Consolidation Chemotherapy Are Associated with Similar Clinical Outcomes to Three Cycles in AML Patients with Favorable Risk Cytogenetics

Background: Patients with core-binding factor acute myeloid leukemia (CBF-AML) have favourable outcomes when treated with standard anthracycline based induction and repeated cycles of cytarabine based consolidation. CBF-AML exhibit high rates of remission, overall survival, and relapse-free survival even without allogenic stem cell transplant (alloSCT). The exact number of consolidation cycles necessary for optimal outcomes, however is unknown. While early studies suggested that 3 or 4 cycles of high dose cytarabine (HiDAC) are associated with better outcomes relative to 1 cycle (Byrd, 1999 & Byrd, 2004), the effects of 2 cycles, has not been studied in this patient group. In this study, we evaluated the impact of 2 cycles of consolidative chemotherapy on the clinical outcomes of patients with CBF-AML.Methods: Prior to 2012 patients with CBF-AML treated in Edmonton, Canada, were intended to receive 2 cycles of HiDAC after a complete remission (CR) following a single induction cycle ± intensification treatment (given if having >5% blasts on a day+14 marrow). Following a change in institutional policy, patients treated after 2012 were intended to receive 3 cycles of consolidation treatment. c-kit testing was not available prior to 2009 but thereafter all patients with c-kit mutations were offered alloSCT in first CR. In contrast, patients treated in Vancouver, Canada underwent similar induction but were intended to receive three consolidative cycles throughout the entire study period. Pooled data was retrospectively analyzed for all patients with CBF-AML treated in these two Canadian centres between 2003-2017 using an intention to treat approach.Results: Overall, 108 patients were identified with a median age of 48 (range 17-75). Sixty-four patients (59%) were male. Seventy-four patients (68.5%) were intended for 3 cycles of consolidation therapy and 34 patients (31.5%) for 2 cycles. There were no differences in baseline characteristics of the analyzed patients (Table 1). There was also no significant difference in the number of patients who received intensification chemotherapy due to day +14 residual disease, the number of induction deaths, or CR rate at end of induction. Six patients intended to receive 2 cycles of consolidation were transplanted in CR1 compared with 5 who were intended to receive 3 cycles (p=0.09). Rates of hospitalization, median length of hospital stay, bacteremic events, intensive care requirements, and deaths during consolidation therapy did not differ significantly between the two groups.Median follow-up time from CR was significantly longer in the 2 consolidation cycle group relative to the 3 consolidation cycle group (85 months vs. 30 months, p<0.0001). Of the 34 patients intended for 2 cycles of consolidation, there were 9 deaths and an additional 4 relapses, for a total event rate of 38.2%. Within the 74 patients intended to receive 3 cycles of consolidation there were 18 deaths and an additional 13 relapses for a total event rate of 41.9% (p=0.83)There was no significant difference in overall survival (p=0.96; Figure 1, 5-year OS 73% for the 2 cycle consolidation group v 71% for the 3 cycle consolidation group), relapse-free survival when censored for transplant (p=0.61; Figure 2, 5-year RFS 63% for the 2 cycle consolidation group v 57% for the 3 cycle consolidation group, or event-free survival (p=0.88; 5-year EFS 54% for the 2 cycle consolidation group v 52% for the 3 cycle consolidation group) within the two groups. Multivariate analysis revealed that patients age, cytogenetics [t(8;21), inv(16)/t(16;16)], or transplantation in CR1 did not influence rates of overall survival or relapse-free survival between the two cohorts.Conclusions: These data suggest that the use of 2 chemotherapy consolidation cycles compared with 3 does not diminish relapse-free survival or overall survival in patients with CBF-AML. Reduction in chemotherapy may provide both economic and quality of life benefits for patients. Larger prospective studies are necessary to confirm these findings. [Display omitted] DisclosuresHogge:Novartis, Roche, and Sanofi: Consultancy.

Weekly CyborD-DARA Is a Safe and Effective Upfront Treatment for Newly Diagnosed Multiple Myeloma. Preliminary Results of the Early Phase 16-Bcni-001/Ctrial-IE (ICORG) 16-02 Study

▪Introduction: Daratumumab (DARA) is a human IgG1k monoclonal antibody licenced for second line use as monotherapy or in combination with either lenalidomide or bortezomib (Bor) plus dexamethasone (D) for patients (pts) who have received at least one prior therapy. There are no published data on front line use of DARA in combination regimens. CyBorD is considered a safe and effective induction regimen for patients with newly diagnosed MM eligible for transplantation. Up to 60% of patients achieve very good partial response (VGPR) or better following 4 cycles of induction (Reeder CB et al, Blood 2010). Since our pre-clinical data showed enhanced antibody dependent cellular phagocytosis (ADCP) following Cyclophosphamide (Cy) exposure (Rigalou et al, ASH 2016), we set out to explore the feasibility of combining DARA with weekly CyBorD in newly diagnosed transplant eligible MM patients. We aim to demonstrate safety, efficacy, convenience and cost-effectiveness in a Phase 1b clinical trial of newly diagnosed patients with MM.Methods: This ongoing phase Ib, open-label, single arm, dose escalation study has recruited 12 patients from November 2016 to June 2017 across 3 sites in Ireland (3 pts in DL 1, 3 pts in DL 2 and 6 pts in DL 3). Baseline demographic factors include: 75% males, 25% females; median age of 57.5 years (35-66 years); 83% ISS stage I, 17% ISS stage II/III. FISH analysis detected t(4;14) in 0% of pts (0/12), t(14;16) in 0% of pts (0/12) and del17p in 17% of pts (2/12). The study is designed to assess the safety and efficacy of 4 cycles of induction therapy with Cy and Bor on days 1, 8, 15 and 22, D 20/mg/day on days 1, 2, 8, 9, 15, 16, 22 and 23 and DARA 16mg/kg on days 1, 8, 15 and 22 for cycles 1 and 2 and on days 1 and 15 for cycles 3 and 4. Following the induction therapy, patients proceed with stem cell mobilization and high dose Melphalan 200mg/m2 autologous stem cell transplant (ASCT). Following SCT 2 cycles of consolidation therapy with Cy and Bor on days 1, 8, 15 and 22, D 20/mg/day on days 1, 2, 8, 9, 15, 16, 22 and 23 and DARA 16mg/kg on days 1 and 15 were administered. After consolidation therapy, all patients are scheduled to receive DARA maintenance on day 1 every 4 weeks until progression, unacceptable toxicity or withdrawal of consent (limited to a maximum duration of 2 years). Patients with high-risk features receive subcutaneous (SQ) Bor on days 1 and 15 during maintenance phase. We used a standard 3+3 design in sequential cohorts (3 dose levels (DL) of Cy and Bor: DL 1: Cy 150mg/m2 and Bor 1.3mg/m2, DL 2: Cy 300mg/m2 and Bor 1.3mg/m2 and DL 3: Cy 300mg/m2 and Bor 1.5mg/m2; and a DL -1: Cy 100mg/m2 and Bor 1.3mg/m2. Six additional patients will be enrolled in an expansion cohort as the maximum tolerated dose (MTD) has been determined as DL 3. The primary endpoints are the incidence of dose limiting toxicity (DLT) within the first cycle of combination at each dose level and complete response (CR) rate post ASCT. Secondary endpoints include: safety, CR rates at the end of induction, consolidation and maintenance, best overall response, minimal residual disease (MRD) negative rate, progression-free survival, clinical benefit rate and overall survival. Response will be investigator-assessed as per IMWG criteria. This trial is registered at www.clinicaltrials.gov as NCT02955810.Results: We report the safety data from interim analysis following completion of the dose escalation phase of CyBorD-DARA trial. The most common adverse events (AE) of grade 3 severity or higher were thrombocytopenia, postoperative wound infection, urinary tract infection, hyponatraemia, back pain, bone pain. Five serious adverse events (SAE) were reported but none related to the study treatment. No DLT occurred in any group. To date all pts continue on treatment and enrolment is ongoing. Although follow up is still short, the combination shows a promising response rate. Following 4 cycles of induction therapy the first 6 patients enrolled (at DL1 and DL2) have achieved VGPR or better. Safety and efficacy data will be updated at ASH meeting.Conclusion: DARA can be safely combined with weekly CyBorD. MTD/RP2D is Cy 300mg/m2 and Bor 1.5mg/m2 in combination with D and DARA and early analysis demonstrates promising efficacy. DisclosuresO'Dwyer:Onkimmune Ltd: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; GlycoMimetics Inc: Research Funding.

A Phase II Study of CPX-351 As a Novel Therapeutic Approach for Patients with Myelodysplastic Syndromes (MDS) after Hypomethylating Agent Failure

Treatment options are limited for patients (pts) diagnosed with MDS at the time of hypomethylating agent (HMA) failure. One goal is to introduce another line of therapy to reduce tumor burden and enable patients to undergo hematopoietic stem cell transplant (HSCT), which may prolong survival for a subset. CPX-351, has shown better overall response rates and improved overall survival in patients with acute myeloid leukemia with underlying MDS changes compared to 7+3, suggesting that CPX-351 can be used in an MDS patient population. We hypothesized that treating MDS pts, who were failed by HMAs or were intolerant with CPX-351 would overcome HMA resistance. This is a phase II study of single agent CPX-351 administered at the standard FDA approved dose of 44 mg/m2 (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) intravenously on days 1, 3, 5 of the induction cycle. If patients achieve complete remission (CR), marrow CR, partial remission or hematologic improvement per 2006 IWG criteria they will be eligible to continue on to consolidation therapy, which consists of CPX-351 at a dose of 15.4 mg/m2 (daunorubicin 15.4 mg/m2 and cytarabine 35 mg/m2) every 28 days. Pts can receive up to 4 cycles of consolidation therapy in the absence of toxicity. The primary objective of the trial is to evaluate the efficacy of CPX-351 as measured by overall response rate (ORR) by IWG 2006 criteria. Secondary objectives include: ,1) determine the time to response (TTR), 2) evaluate the duration of response (DOR), 3) evaluate the event-free survival and the overall survival probability during trial period. Pts are risk stratified into lower vs higher-risk prior to enrollment using the Post-HMA model (Nazha A, et al. Hematologica 2016). Eligibility includes: pts &amp;gt;18 years with primary or secondary resistance to HMA, ECOG performance status &amp;lt; 2 and adequate organ function. Pts are excluded if they have uncontrolled infection or active malignancy. A total of 18 pts will be enrolled to each arm (lower and higher risk). To date, three pts were enrolled. One with MDS refractory to HMA who achieved complete remission and proceeded with 4 cycles of consolidation. The pt remained in remission 6+ months after the completion of consolidation. Another patient achieved a marrow CR but had a fungal pneumonia and then was taken off the trial (patient choice for going to hospice). The third patient had MDS/MPN, completed induction and achieved stable disease with improvement in platelets and neutrophils. All patients were lower-risk per the stratification model. No unexpected toxicity was observed. In conclusion, preliminarily CPX-351 is effective in MDS patients after HMA failure who are eligible to receive intensive chemotherapy. The treatment was well tolerated and toxicities were similar to what was observed in pivotal CPX-351 trials. The trial is ongoing and the results will be updated in the meeting. Disclosures Nazha: MEI: Other: Data monitoring Committee; Novartis: Speakers Bureau; Incyte: Speakers Bureau; Jazz: Research Funding. Mukherjee:Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EUSA Pharma: Consultancy; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Bristol Myers Squib: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Aplastic Anemia and MDS International Foundation: Honoraria. Advani:Abbvie: Research Funding; Macrogenics: Research Funding; Glycomimetics: Consultancy, Other: Steering committee/ honoraria, Research Funding; Immunogen: Research Funding; Seattle Genetics: Other: Advisory board/ honoraria, Research Funding; Amgen: Consultancy, Other: steering committee/ honoraria, Research Funding; Kite: Other: Advisory board/ honoraria; Pfizer: Honoraria, Research Funding; Novartis: Consultancy, Other: advisory board; OBI: Research Funding; Takeda: Research Funding. Carraway:Jazz: Consultancy, Speakers Bureau; BMS: Consultancy, Other: Research support, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Takeda: Other: Independent Advisory Committe (IRC); Novartis: Consultancy, Speakers Bureau; Abbvie: Other: Independent Advisory Committe (IRC); ASTEX: Other: Independent Advisory Committe (IRC). Gerds:AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding; Roche/Genentech: Research Funding; CTI Biopharma: Consultancy, Research Funding; Imago Biosciences: Research Funding; Sierra Oncology: Research Funding; Celgene: Consultancy, Research Funding; Gilead Sciences: Research Funding; Apexx Oncology: Consultancy; Pfizer: Research Funding. Patel:Alexion: Other: educational speaker. Sekeres:Takeda/Millenium: Consultancy; Pfizer: Consultancy; BMS: Consultancy. OffLabel Disclosure: CPX-351 in MDS

Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML)

Study Background: The presence of minimal residual disease (MRD) after IC in AML patients is often a harbinger of relapse, and therapeutic targeting of MRD has emerged as an important strategy to improve long-term outcomes. The importance of the PD-1/PD-L1 pathway in immune evasion of AML has been demonstrated in murine AML models whereby PD-L1 and PD-1 were upregulated in leukemia cells, and PD-1 blockade suppresses invivo leukemia cell proliferation and improved survival in AML bearing mice (Zhang et al., 2009; Zhou et al., 2010). Combining IC with immune checkpoint inhibition (ICPI) has resulted in a significant clinical activity in some advanced solid malignancies including non-small-cell lung cancer. A recent single-arm phase 2 study combining IC with nivolumab showed the combination was feasible and resulted in undetectable MRD in 53% of patients with Complete response (CR)/CR with incomplete count recovery (CRi) (Ravandi et al, 2019). Here we report on the design of the first randomized multi-center clinical trial of IC+ICPI in fit AML patients. Methods: The primary objective of this investigator-initiated Cancer Therapy Evaluation Program (CTEP)-sponsored multi-institutional, randomized phase II study (NCT04214249) is to assess the percentage of patients with MRD negative CR (MRD- CR) as measured by flow cytometry at the end of first cycle of consolidation therapy with IC+ pembrolizumab and compare between the two study arms (Figure 1). Secondary objectives include rates of CR/CRi, complete remission with partial recovery count (CRh) and hematologic improvement (HI) to red blood cells and platelets, MRD negativity at Day 14, MRD-negative CR at end of induction therapy and MRD negative CR after last consolidation cycle, event free survival (EFS), relapse free survival (RFS), duration of response (DOR), and overall survival (OS), and proportion of patients who develop severe toxicity. Important exploratory objectives include MRD assessment by duplex sequencing (DS) and comparing DS and multiparameter flow cytometry for MRD detection. The study will consist of an induction, consolidation, and maintenance phase of therapy. A total of 124 patients will be included (62 patients in the intervention arm and 62 patients in the control arm). Planned stratification factors include 1) age (younger than 65 vs. 65 and older), 2) cytogenetics by FISH or metaphase karyotype (presence vs. absence of core binding factor inversions and translocations), and 3) t-AML or AML arising from prior/antecedent MDS. All patients will receive cytarabine at 100 mg/m2/day continuous infusion on Days 1-7 and either idarubicin 12 mg/m2/day IV on Days 1-3 or daunorubicin 60 mg/m2/day IV on Days 1-3. on Day 8 of the induction chemotherapy, half of the patients will receive pembrolizumab IV (intervention arm), and continue Q3 weeks throughout Induction/Consolidation, and thereafter for up to 2 years from the start of maintenance. The other half will not receive pembrolizumab (control arm). After 31 efficacy-evaluable patients (patients who had a bone marrow biopsy done after the first consolidation cycle) in each of the two study arms have had their primary endpoint results available, a formal futility and toxicity analysis will be conducted. Follow up will continue up to 2 years after the last patient is randomized. Eligible patients are aged ≥18 and ≤75 years with newly diagnosed and pathologically-confirmed AML, including secondary AML arising from prior MDS and therapy-related AML. Patients with FLT3-mutated AML are excluded as well as those with prior allogeneic stem cell transplant, active infection requiring systemic therapy, and requiring use of high dose corticosteroids. Responses in AML patients will be assessed using European Leukemia Net 2017 response criteria. EFS will be calculated as the time from initial treatment to either disease relapse or death. OS will be calculated from time from initial treatment to death. Biomarker analyses will include an extensive array of immunologic and correlative studies that will evaluate PD-1 and PD-L1 expression, immune cell subset analysis, leukemia specific T-cell response, cytokine level, T-cell receptor (TCR) repertoire, as well as RNA-seq, gut microbiome characterization and metabolomics, and whole exome sequencing for tumor and germline DNA. Figure 1 Disclosures Zeidan: Epizyme: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Cardinal Health: Consultancy, Honoraria; Acceleron: Consultancy, Honoraria; Leukemia and Lymphoma Society: Other; Jazz: Consultancy, Honoraria; Celgene / BMS: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; BeyondSpring: Consultancy, Honoraria; Cardiff Oncology: Consultancy, Honoraria, Other; Takeda: Consultancy, Honoraria, Research Funding; Ionis: Consultancy, Honoraria; MedImmune/Astrazeneca: Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Aprea: Research Funding; ADC Therapeutics: Research Funding; Astex: Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Taiho: Consultancy, Honoraria; CCITLA: Other; Novartis: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria. Radich:Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Jazz: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding.

Acquired hemophilia A and plasma cell neoplasms: a\xa0case report and review of the\xa0literature

BackgroundAcquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare.Case presentationWe describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered treatment of the plasma cell neoplasm necessary, and a VRD (bortezomib, lenalidomide, and dexamethasone) regimen was initiated. Due to multiple complications, VRD was reduced to VRD-lite after two cycles. After nine cycles of induction therapy and five cycles of consolidation therapy, the patient is in complete remission of his acquired hemophilia A and very good partial remission of the plasma cell neoplasm. We conducted a literature review to identify additional cases of this rare association and identified 15 other cases. Case descriptions, including the sequence of occurrence of acquired hemophilia A and plasma cell neoplasm , treatment, evolution, and outcome are presented.Discussion and conclusionsOur case, together with 15 other cases described in the literature, underscore the possibility of plasma cell neoplasm as an underlying cause of acquired hemophilia A. Physicians should consider including protein electrophoresis, immunofixation, and analysis of free light chains in laboratory diagnostics when treating a patient with acquired hemophilia A. The occurrence of excessive and unexplained bleeding in patients diagnosed with plasma cell neoplasm should raise suspicion of secondary acquired hemophilia A and trigger the request for coagulation tests, particularly in patients treated with immunomodulatory drugs such as thalidomide or lenalidomide. Additionally, early intervention with immunoadsorption can be lifesaving in cases with high-titer factor VIII inhibitors, especially when surgical interventions are necessary.

A Phase 2 Study with Minimal Residual Disease (MRD) Driven Adaptive Strategy in Treatment for Newly Diagnosed Multiple Myeloma with Upfront Daratumumab-Based Therapy

Background: Minimal Residual Disease (MRD) was clearly demonstrated as a prognostic marker for prognosis in multiple myeloma and has been integrated into IMWG clinical guidelines as one of the response criteria. There is however no consensus yet when and how to use MRD data in clinical practice throughout treatment course. Daratumumab was approved by FDA in different settings after it had been shown as a highly effective agent with a reasonable safety profile in myeloma treatment. It also showed impressive data to achieve MRD negativity. We plan to use the combination of daratumumab, lenalidomide, and dexamethasone upfront, with the addition of Velcade for consolidation if needed, in newly diagnosed multiple myeloma (NDMM) patients. We propose to use an MRD driven adaptive strategy for decision making in myeloma treatment and use daratumumab-based frontline therapy. Trial Design and Methods: We designed this prospective, single-arm, multi-center, phase 2 trial. The primary objective is to determine the rate of MRD negativity after daratumumab-based induction and consolidation therapy if necessary in both transplant eligible and ineligible NDMM patients. The secondary objective is to describe the overall survival, progression free survival, MRD conversion rate after consolidation, quality of life for patients, safety and tolerability of daratumumab-based combination regimens in both transplant eligible and ineligible patient populations, estimation of a successful stem cell mobilization after receiving daratumumab-based induction therapy. The primary endpoint will be MRD-negativity after six cycles of induction, followed by three cycles of consolidation therapy if MRD is positive after induction. We will seek to establish evidence that the true proportion of patients who can achieve MRD negativity after induction + consolidation (if still MRD+ after induction) is high, which we define as any response rate that is at least 23%. Patients with NDMM meeting IMWG diagnostic criteria are eligible for this trial, regardless of transplant candidacy. Patient will have stem cell collection after induction therapy. We will follow the patients' treatment response using IMWG response criteria including MRD status through induction, consolidation, transplant (if applied) and maintenance. Patient will come off the study if disease progression per IMWG response criteria. We plan for MRD testing by next generation sequencing and flow cytometry. This study will enroll 50 eligible patients. A two-stage design will be conducted, with an interim futility analysis after the primary endpoint is available on the first 20 enrolled patients. We will proceed to a final analysis with all 50 patients if at least 2/20 (10%) of patients achieve MRD negativity after consolidation. This trial is anticipated to be open at four academic centers. Conclusion: This multicenter phase 2 trial will apply a novel clinical trial design with an adaptive strategy to treat newly diagnosed myeloma patients based on MRD results. Therapeutic advance with Daratumumab-based combination regimen as frontline therapy may help myeloma patients to achieve higher rate of MRD negativity. Figure Disclosures Ye: AbbVie: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Onyx: Research Funding; Sanofi: Research Funding; Karyopharm: Research Funding; Janssen: Research Funding; MingSight: Research Funding; Portola Pharmaceuticals: Research Funding. Anderson:Amgen, Janssen, Takeda, Celgene: Consultancy, Speakers Bureau. Lipe:amgen: Research Funding; amgen: Consultancy; Celgene: Consultancy. Talpaz:Samus Therapeutics: Research Funding; Imago BioSciences: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CTI BioPharma: Research Funding; Constellation: Research Funding; Incyte: Research Funding; Novartis: Research Funding.

Ixazomib or Lenalidomide Maintenance Following Autologous Stem Cell Transplantation and Ixazomib, Lenalidomide, and Dexamethasone (IRD) Consolidation in Patients with Newly Diagnosed Multiple Myeloma: Results from a Large Multi-Center Randomized Phase II Trial

Ixazomib or Lenalidomide Maintenance Following Autologous Stem Cell Transplantation and Ixazomib, Lenalidomide, and Dexamethasone (IRD) Consolidation in Patients with Newly Diagnosed Multiple Myeloma: Results from a Large Multi-Center Randomized Phase II Trial

Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

469P - Comparison of combined chemoradiotherapy regimens; Paclitaxel plus carboplatin and cisplatin plus etoposide for locally advanced non-small cell lung cancer: A randomised phase III trial

BackgroundThe optimal chemotherapy regimen to use with radiotherapy in stage III non–small cell lung cancer (NSCLC) is still unknown. This phase III comparative randomized trial was conducted to determine the optimal chemotherapy regimen with standard daily concurrent thoracic radiation therapy (CTRT), in patients with locally advanced unresected stage III NSCLC. MethodsWe recruited 188 patients aged 18–81 years with stage III, histologically confirmed NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, an estimated life expectancy of greater than 3 months, and adequate organ function from January 2011 to December 2018. Patients were randomised (1:1) to paclitaxel plus carboplatin and cisplatin plus etoposide arms. ResultsPatients with unresected stages IIIA and IIIB NSCLC received carboplatin (AUC=2) and paclitaxel (45 mg/m2) given weekly with CTRT (63 Gy) followed by two cycles of consolidation therapy (carboplatin AUC=6, paclitaxel 200 mg/m2) (arm CP) and cisplatin (50 mg/m2 on days 1, 8, 29, and 36) plus etoposide (50 mg/m2 daily on days 1 to 5, and 29 to 33) with CTRT followed by consolidation cisplatin plus etoposide (arm EP) were included. On hundred eighty eligible patients were evaluated. With median follow-up time of 41.7 months, median overall survival was 19.8 and 18.1 months for arms CP and EP, respectively (P = 0.279). But patients in arm EP, compared with patients in arm CP, had more grade 4 neutropenia (18.5% vs 11,1%, p < 0.001), grade 4 naussea/vomiting (18,5% vs 15.3 %, p < 0.001) grade 3-4 mucositis/esophagitis (23,4% vs 15,3%, p < 0.001) and acute kidney disease (27.1% vs 15,1%, p < 0.001). ConclusionsIn patients with stage III NSCLC treated with cisplatin plus etoposide and carboplatin plus paclitaxel had similar overall survival, but cisplatin plus etoposide arm was associated with increased toxicity. Legal entity responsible for the studyEast Mediterranean Oncology Initiation. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia

BackgroundCytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML). In this study, we conducted a retrospective study in adult AML patients with newly diagnosed with de novo AML who did not undergo HSCT, to study long term relapse free survival (RFS) and overall survival (OS) after consolidation chemotherapy.MethodsWe recruited 141 consecutive AML patients during January 2010–June 2017, the patients received induction chemotherapy with standard dose Ara-C and Idarubicin (7 + 3 or 5 + 2 regimen) followed by intermediate (IDAC) or high dose Ara-c (HiDAC) consolidation therapy.ResultsNormal karyotype, complex, favorable, intermediate and adverse chromosomal aberrations were found in 59%, 16%, 5%, 14% and 6%, respectively. Mutated NPM1, FLT3-ITD and CEBPA genes in CN-AML were seen in 33%, 18% and 19%, respectively. A 5 year follow up, 5y-RFS was 16% and 5y-OS was 14% in the whole study population. 5y-RFS and 5y-OS in patients completed 4 cycles of consolidation therapy were 25% and 40%, respectively. Adverse cytogenetic risk and mutated FLT3-ITD were significantly associated with poor RFS (9 and 15 months, respectively) and OS (14 and 16 months, respectively), whereas patients with mutant NPM1 had favorable outcomes (RFS/OS = 51/63 months). Patients receiving 4 cycles of consolidation therapy had significantly impacts on median RFS and OS compared with those treated with 1 or 2 cycles; 15 versus 11 months (p = 0.006) and 31 versus 15 months (p < 0.001), respectively.ConclusionsCytogenetic and mutation tests for FLT3-ITD, NPM1 and CEBPA genes were meaningful for predicting outcomes in adult AML patients. Adverse cytogenetic abnormalities and FLT3-ITD mutation showed dismal RFS and OS.

Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation Is Safe, Effective, and Leads to MRD-Negative Complete Remissions

Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation Is Safe, Effective, and Leads to MRD-Negative Complete Remissions

Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial

Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial

Cybord-Dara Is a Highly Effective Upfront Treatment for Newly Diagnosed Multiple Myeloma. Initial Efficacy Results of the 16-Bcni-001/Ctrial-IE (ICORG) 16-02 Study

Introduction: Daratumumab (DARA), a human IgG1k monoclonal antibody with single activity in multiple myeloma (MM) shows strong synergy in combination with other anti-MM agents, including immunomodulatory drug (IMiDs) and proteasome inhibitors (PI). This has led to the exploration of DARA in combination with front line regimens. Triplets including a PI and an IMiD are considered an ideal backbone with which to combine DARA prior to Autologous Stem Cell Transplantation (ASCT). However, based on the ability of Cyclophosphamide (Cy) to enhance DARA mediated antibody dependent cellular phagocytosis, we hypothesized that CyBorD may provide an alternative option (Naicker, ASH 2017). We are currently exploring the preliminary safety and efficacy of CyBorD and DARA as part of an ongoing phase 1b study in newly diagnosed MM (NDMM) pts eligible for ASCT. Last year we reported on the safety of this combination with an absence of dose limiting toxicity (DLT) with weekly subcutaneous (SQ) Bortezomib (Bor) 1.5mg/m2, Cy 300mg/m2 and DARA 16mg/kg (McEllistrim, ASH 2017). We now report on the efficacy of this regimen as pre-transplant induction, including the rate of CR post ASCT.Methods: Pts received 4 cycles of induction therapy with weekly CyBorD and DARA 16mg/kg weekly for cycles 1 and 2 and every 2 weeks for cycles 3 and 4. Following induction therapy, pts proceeded to stem cell mobilization and ASCT followed by 2 cycles of consolidation therapy with weekly CyBorD plus DARA 16mg/kg on days 1 and 15. Following completion of consolidation therapy, all pts receive DARA maintenance every 28-days for 2 yrs or until progression, unacceptable toxicity or withdrawal of consent. Pts with high-risk features receive Bor on days 1 and 15 during maintenance phase. The primary endpoints were the incidence of DLT within the first cycle of combination at each dose level and CR rate post ASCT. Secondary endpoints included: safety, CR rate at the end of induction, consolidation and maintenance, best overall response, minimal residual disease (MRD) negative rate, progression-free survival, clinical benefit rate and overall survival. Responses were investigator-assessed as per IMWG criteria. This trial is registered at www.clinicaltrials.gov as NCT02955810.Results: Eighteen pts were enrolled between Nov 2016 and Dec 2017 and received at least 1 dose of treatment. Baseline characteristics were: median age = 56 y (range 32-66); M (61%), F (39%), ISS stage I, II, III in 78%, 17% and 6% of pts, respectively. 28% patients were identified with high risk genetic features [17p deletion and/or t(4;14) by FISH and/or SKY92 (SkylineDx)]. Three patients discontinued therapy early (primary refractory, persistent liver toxicity, death, respectively).Overall, treatment was well tolerated. The most common grade (gr) 3/4 hematologic treatment emergent adverse events (TEAE) were lymphopenia (44%), neutropenia (11%) and anemia (11%). The most common gr 3/4 non-hematologic TEAE were diarrhea (11%) and infection (61%). One patient died from gr 5 diffuse alveolar damage 7 weeks post ASCT. A single patient developed gr 3 liver toxicity. DARA-associated infusion reactions were ≤ gr 2 (11%).On an intent to treat (ITT) basis 94% achieved ≥ very good partial response (VGPR) with ≥ complete response (CR) in 44% pts (Figure). Among the sixteen patients completing 4 cycles of induction ORR was 100%, ≥ VGPR (69%), ≥ CR (13%). Informative NGS data (Adaptive Biotech) are available on 11/16 patients post induction, of whom 100% are MRD negative post induction at a level of ≥ 10e4. Following the induction phase 15/16 patients readily mobilized sufficient CD34 positive progenitors and proceeded to ASCT, one patient failed repeated mobilization. One patient died prior to post ASCT response assessment and data on the last patient is pending. Thus 13/15 patients are currently evaluable for response post ASCT. Responses deepened post ASCT with 100% achieving ≥ VGPR and 62% achieving ≥ CR. Based on EBMT criteria the CR/nCR rate post ASCT was 92%. Post ASCT PET-CT scans were consistent with complete metabolic response in all 13 patients. Updated results, including MRD status post ASCT will be presented at the meeting.Conclusions: CyBorD-DARA is a highly active, well tolerated induction therapy for NDMM patients undergoing ASCT. These data support the further development of this combination as a convenient, cost effective alternative to PI-IMiD-DARA based combinations. [Display omitted] DisclosuresQuinn:Janssen: Honoraria. O'Dwyer:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Glycomimetics: Research Funding; Onkimmune: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding.

Allogeneic Hematopoietic Cell Transplantation (HCT) Vs. Non-HCT Consolidation Therapies in Acute Myeloid Leukemia (AML) Patients 60-75 Years of Age in First Complete Remission (CR1): An Alliance (A151509), SWOG, ECOG-ACRIN and CIBMTR Study

Introduction: The preferred post-remission therapy for older patients (pts) with AML remains uncertain. We compared outcomes for older AML pts in CR1 receiving HCT reported to the CIBMTR to older AML pts achieving CR1 on National Clinical Trials Network induction and non-HCT consolidation therapy (CT) trials.Methods: This study focused on pts 60-75 years of age treated between 2004 to 2013. CT pts (n=211) underwent induction and consolidation on Alliance for Clinical Trials in Oncology, ECOG-ACRIN or SWOG clinical trials for initial therapy for newly diagnosed AML; the CIBMTR provided data for HCT pts (n=431). CT patients received at least one cycle of CT on study and were excluded if HCT occurred at any time. Time to event started at CR1 and pts entered at CT or HCT, respectively, using left-truncation to account for differential entry times.Results: For the CT cohort, first consolidation included standard therapy (e.g., cytarabine or a hypomethylating agent) and additional study drug (e.g., bortezomib, dasatinib, sorafenib, and Zosuquidar, gemtuzumab) or tipifarnib alone. Among HCT pts, the donor was a HLA-matched sibling or unrelated donor (URD) in 66% and the others were partially HLA-matched/mismatched URD (10%) or cord blood (24%). HCT pts were younger and more frequently had high-risk AML (high WBC, secondary AML and unfavorable cytogenetics) (Table). The median time from CR1 to HCT and CT was 3.2 and 0.5 months, respectively.Allogeneic HCT showed worse overall survival (OS) (HR=1.52, p=0.02) prior to 9 months and better OS thereafter (HR= 0.53, p <0.0001) relative to CT (figure 1A). Treatment-related mortality (TRM) was worse after HCT in the first 9 months (HR=2.8, CI: 1.5 -5.2, p=.0009), while relapse was less frequent beyond 9 months after treatment (HR = 0.42, CI: 0.29 to 0.61, p<.0001). Despite higher early TRM, HCT recipients went on to manifest superior OS [5 year OS: HCT 29% (24-34%), CT 13.8% (9 -22%)] (Figure 1A). The benefit of HCT for survival after 9 months was more prominent in those with unfavorable cytogenetics (Figure 1B). Multivariate analysis for OS showed no statistically significant effect of age or performance status, while unfavorable cytogenetics were detrimental (HR=1.74, p<.0001).Conclusions. Allogeneic HCT led to heightened early risks from TRM, but resulted in superior long-term survival in older AML pts receiving HCT relative to CT by reducing relapse. Efforts to attenuate early TRM after allogeneic HCT may further improve HCT outcomes for older pts. [Display omitted] DisclosuresUstun:novartis: Speakers Bureau. Attar:Agios: Employment, Equity Ownership. Larson:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BristolMyers Squibb: Consultancy, Research Funding; Ariad/Takeda: Consultancy, Research Funding. Roboz:Roche/Genentech: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Aphivena Therapeutics: Consultancy; Sandoz: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; AbbVie: Consultancy; Celltrion: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Pfizer: Consultancy; Celgene Corporation: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Roche/Genentech: Consultancy; Orsenix: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Orsenix: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; AbbVie: Consultancy. Uy:GlycoMimetics: Consultancy; Curis: Consultancy. Stone:Fujifilm: Consultancy; Ono: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Agios: Consultancy, Research Funding; AbbVie: Consultancy; Argenx: Other: Data and Safety Monitoring Board; Celgene: Consultancy, Other: Data and Safety Monitoring Board, Steering Committee; Arog: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz: Consultancy; Astellas: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Sumitomo: Consultancy; Amgen: Consultancy; Cornerstone: Consultancy. Foran:Agios: Research Funding; Xencor, Inc.: Research Funding. Weisdorf:Seattle Genetics: Consultancy; Equillium: Consultancy; FATE: Consultancy; SL Behring: Consultancy; Pharmacyclics: Consultancy.