ALBERT

Description: Steroid-refractory chronic graft-versus-host disease (cGvHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase-2 clinical trial to determine safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGvHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide, 0.5 mg/d; LD) orally (n=17) or 2 mg/d at a starting dose of 0.5 mg/d increasing to 2 mg/d over 6 weeks (n=17, HD). Primary endpoint was overall response rate (ORR) at 6 months according to the 2005 NIH cGvHD Response Criteria. Thirty-two had severe sclerotic skin and received a median of 5 (range, 2-10) prior systemic therapies. ORR was 47% (95% confidence interval [95% CI], 30, 65%) in intent-to-treat analyses. All were partial responses with no difference in ORR between the cohorts. ORR was 67% (45-84%) in the 24 evaluable subjects at 6 months. Nine had improvement in NIH joint/fascia scores (p=0.018). Median change from the baseline in body surface area (BSA) of involved skin cGvHD was -7.5% (-10 to +35; p=0.002). The most frequent adverse events (AEs) were lymphopenia, infection, and fatigue. Eight subjects in the HD cohort had dose decreases because of AEs. There was one death in the LD cohort from bacterial pneumonia. Our data indicate anti-fibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and IL-2. Pomalidomide, 0.5 mg/d, is a safe and effective therapy of advanced corticosteroid-refractory cGvHD.

Description: Immune escape from graft-versus-tumor (GVT) contributes to relapse after allogeneic stem cell transplantation (SCT). High-dose radiation (XRT) mobilizes a tumor-specific immune response following direct damage to the tumor and microenvironment. Radiation's abscopal effect is also immune mediated. We hypothesized that local radiation of relapsed tumor would rekindle a GVT effect and yield abscopal tumor responses. We tested the safety and systemic effects of single-fraction XRT followed by donor lymphocyte infusion (DLI) in patients with lymphoid malignancy and refractory relapse after SCT. Eligible subjects (Table) had tumor progression following donor engraftment, withdrawal of immune suppression and/or DLI, and XRT-amenable tumor. Subjects received 8 Gy XRT to 1 or more tumors; all but 1 (with chronic GVHD) received DLI 24 hours later. Clinical monitoring included marrow function, GVHD, XRT toxicity and tumor response. Correlative monitoring for systemic immunologic and GVT effects included FDG-PET imaging, serial peripheral blood sampling, and biopsy of radiated and nonirradiated tumor. Immune effects were characterized by flow cytometry and gene expression analysis. Local XRT toxicity of Grade 3 or less presented as expected in all subjects. Grade 4 neutropenia (2) was transient and GCSF-responsive; GVHD flare was not observed. Unexpected toxicity was observed in 1 subject who developed Grade 4 diffuse alveolar hemorrhage and Grade 3 cardiomyopathy that responded to therapy. Sustained response in radiated sites was observed in 6 of 8 evaluable subjects (nonevaluable: 1 MM bony lesion; 1 subject received further Rx). RECIST responses outside the radiation field included 2 PR and 5 SD. 2 subjects with SD had regression after initial tumor flare. 3 of 4 regressions were transient, with progression by 6 months; 3 subjects demonstrated progression. A single subject who received radiation alone demonstrated systemic tumor response as well as improvement in chronic GVHD (sclerotic skin). By FDG-PET, all subjects' radiated tumors showed substantially decreased uptake at D28; SUV changes were variable at D7. Changes in non-XRT tumors demonstrated far greater variability, even within single subjects. Consistent with systemic immune activation resulting from radiation-DLI therapy, within 1 week, peripheral blood T cell proliferation (%Ki-67+) increased significantly in CD4 and CD8 T cells, as well as FoxP3+ Tregs (Wilcoxon paired nonparametric analyses; p =.004, .004 and .01, respectively). A trend (p=.078) toward increased frequency of Th1 effector CD4 cells (T-bet+CD28-) was also observed. Comparison of gene expression in nonirradiated (abscopal) tumor in 4 patients collected pre and 1 month post XRT was consistent with an IFN-mediated response to cell damage. Genes were upregulated for receptors for nuclear materials released by damaged cells (TLR2, TLR4, CLEC4E), high- and low- affinity FcgR (FCGR1A and FCGR2A) used for phagocytosis, and an annexin receptor for phagocytic cells (FPR2). The inflammasome component genes NLRP3 and CASP1 were upregulated, as was IFIT1, a Type 1 IFN inducible gene. After SCT, XRT results in local tumor regression; abscopal responses were also observed, with systemic immune responses suggested by T cell proliferation in the peripheral blood and upregulation of tissue damage receptors and IFN-inducible genes in nonirradiated tumor. Systemic tumor responses were delayed, with peak regression occurring 3-4 months after XRT, consistent with an immune-mediated effect. GVHD was not observed; significant, reversible pulmonary and marrow toxicities were infrequent. Transient abscopal responses in these DLI-refractory patients suggest plausible synergy between radiation and allogeneic GVT effects. Further investigation into posttransplant immunomodulatory radiation is warranted. Funding: Intramural NCI/CCR and NCI Contract No. HHSN261200800001E Table 1. DX Age/Sex Years Post-Allo XRT Site Donor / DLI CD3 Dose (10e6) XRT Response NonXRT Response NonXRT Response Duration CLL 65/M 2.3 B Neck, L Groin URD/1 -90% -69% 2M HL 36/M 2.8 B Axillae MRD/10 -6% +51% CLL 64/M 1.4 R Axilla URD/1 -82% -19% 3M HL 37/M 7.0 R Axilla MRD/10 -69% +2% 4M MM 60/F 6.9 R Ileum MRD/10 NE PD - HL 25/F 1.2 Lumbar 3-5 URD/1 7% -69% 3M HL 37/F 5.8 R Neck MRD/10 -100% -30% 3M HL 27/M 2.7 L Pelvis MRD/10 NE NE - MCL 57/M 3.1 L Groin URD/1 -100% +28% HL 28/M 1.8 L Neck MRD/None -73% -9% 3M Disclosures No relevant conflicts of interest to declare.

Description: Introduction Despite recent advances in treatment, acute myeloid leukemia (AML) remains difficult to cure with high rates of relapse. Relapsed/refractory AML patients who are elderly or unfit for cytotoxic chemotherapy and whose disease fails to respond to hypomethylating agents represent an unmet need, and new safe and effective treatment options are needed for this patient population. Aspartate β-hydroxylase (ASPH) is a transmembrane protein that hydroxylates aspartyl and asparaginyl residues of epidermal growth factor (EGF)-like protein domains, and promotes cellular motility, migration, and adhesion. ASPH is highly expressed during fetal development and in placental trophoblasts, but not in any other healthy adult human tissue. ASPH is uniquely upregulated in cancer cells and is reported to be overexpressed in over 20 different solid neoplasms, in which it propagates a malignant phenotype, and is associated with increased cell proliferation, invasiveness, and poor prognosis. ASPH is therapeutically targetable via a fully human monoclonal antibody against ASPH, SNS-622. Subsequently, SNS-622 antibody-drug conjugates (ADCs) and a vaccine have been developed and are under current preclinical and clinical testing, respectively. We have previously demonstrated ASPH overexpression on the MOLM-14 AML cell line and effective in vitro killing of these cells using SNS-622 ADCs. In an effort to further characterize ASPH as a therapeutic target in AML, we report here the first study of ASPH expression patterns in AML patient samples. Methods Bone marrow (BM) aspirate and peripheral blood (PB) samples were collected from AML patients during 2014-2018 on a University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC) tissue banking protocol. Mononuclear cells were isolated by density centrifugation and were viably cryopreserved at -80ᵒC. Samples were analyzed using 8-color multiparameter flow cytometry to assess cell surface expression of ASPH, using fluorescein isothiocyanate (FITC)-conjugated SNS-622. The remainder of the fluorophores were labeled with standard lineage-specific markers. Expression of ASPH was measured via FITC fluorescence for each cell population and analyzed by two blinded, independent reviewers using FlowLogicTM software. Statistical analysis of ASPH expression was conducted using IBM® SPSS® Statistics for Windows, release 25.0.0 (IBM Corp., Armonk, N.Y., USA). Cohen's kappa (κ) was used to quantify the inter-observer agreement between two independent observers. Visual inspection of the expression data for the whole patient population showed a bimodal distribution, which was used to identify a robust cut-point separating high (i.e. positive) from low (i.e. negative) ASPH expression. Results Forty-two AML patient samples were evaluated (32 BM, 10 PB). Median patient age was 66 years, 48% (n=20) were female, 69% Caucasian and 21% African American. Disease status was 52% untreated de novo, 19% untreated secondary from antecedent MDS or MPN, and 29% relapsed/refractory. Samples were cytogenetically and molecularly diverse - with 50% exhibiting normal and 14% complex karyotype; 38% FLT3-ITD or FLT3-TKD, 29% NPM1, 19% IDH1/2, and 10% TP53 mutations. Full patient characteristics are shown in Table 1. Myeloblast expression of ASPH was found in 38% of samples (n=16; 14 BM, 2 PB) with a mean fluorescent intensity (MFI) of 10 as a cutoff for ASPH surface expression positivity. ASPH expression was not seen on other non-neoplastic cells including CD34+ hematopoietic stem cells, B- or T-lymphocytes, and monocytes. A blinded, independent review of the data revealed a Cohen's kappa (κ) of 0.74 with standard error of the estimate of ± 0.11. Patients with AML with ASPH expression were clinically heterogeneous, with no correlation between ASPH expression and AML subtype, karyotype or mutation status (Table 1). Conclusion ASPH is overexpressed in approximately 40% of patients with AML and serves as a promising therapeutic target. An ASPH nanoparticle vaccine is currently under clinical investigation and has shown promising results in solid tumors. We plan to expand clinical testing of targeting ASPH to AML. The ASPH positivity cutoff established via this work will serve as the eligibility criterion for the planned phase Ib/IIa of anti-ASPH vaccination in AML. . Disclosures Lebowitz: Sensei Biotherapeutics: Employment. Malhotra:Sensei Biotherapeutics: Employment. Fuller:Sensei Biotherapeutics: Employment. Shahlaee:Sensei Biotherapeutics: Equity Ownership; Sensei Biotherapeutics: Consultancy. Ghanbari:Sensei Biotherapeutics: Employment; Sensei Biotherapeutics: Equity Ownership. Emadi:NewLink Genetics: Research Funding.

Description: Introduction Acute myeloid leukemia (AML) is a heterogeneous disease that depends on precise risk-stratification for predicting outcomes and optimizing therapy plans. Despite the current clinical landscape of incorporating karyotype and mutations into prognostic models, chemosensitivity (or lack thereof) is usually not evaluated or appreciated until a patient undergoes a day 14 bone marrow (D14BM) evaluation during induction treatment. While the D14BM aspirate and biopsy are regularly used to predict achievement of CR versus need for further reinduction therapy, some have questioned its utility. Further, the invasive nature of the procedure leads to significant patient discomfort, anxiety, increased risk of complications (infections, bleeding, damage to surrounding tissues) and, at times, is not feasible due to a patient's critical state. Therefore, alternative criteria are needed to help risk-stratify these patients and predict treatment responses. We report here a single center analysis of the relationship between the rate of peripheral blood blast (PBB) clearance with cytotoxic induction therapy and clinical outcomes. Methods Patients diagnosed with AML (non-M3) with detectable PBB via manual differential or flow cytometry at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC) during 2007-2018 were identified. Only patients who underwent induction with a "7+3" regimen with cytarabine and an anthracycline (idarubicin or daunorubicin), or "7+3" plus a third agent, were included. Patient and disease characteristics, treatment courses, and clinical outcomes were collected. The absolute PBB count was calculated by percent PBB multiplied by total leukocyte count (103/mcL). PBB rate of clearance (PBB-RC) was defined as the percentage of the absolute PBB count at diagnosis that was cleared each day, on average, until clearance or D14 of induction chemotherapy. Patients were divided into three groups based on PBB-RC: high, if PBB-RC 〉30% (n=15); low, if PBB-RC

Description: Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are known complications of chimeric antigen receptor T-cell (CAR-T) therapy. These clinical syndromes develop as a result of CAR-T activation, proliferation, and tumor lysis with resultant cytokine secretion. In prior reports of CD19 CAR-T therapy patients, those who developed ICANS showed evidence of endothelial activation and disruption of the blood-brain barrier as a result of cytokine release while only approximately one-third demonstrated changes on Brain MRI (Gust et al. Cancer Discov 2017). As such, further predictive markers and studies are needed to identify patients at risk for ICANS to allow for expedited management and improved outcomes. Herein we report a single-center analysis exploring glycolytic activity on PET/CT and the association with clinical outcomes for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) after CAR-T therapy. Methods: An organ-based evaluation of uninvolved sites was conducted in R/R DLBCL patients (n=32) who underwent CD19 CAR-T therapy with evaluable PET/CT imaging at baseline immediately prior to CAR-T therapy and at 30 days post-infusion (D+30). All patients in this analysis were treated with axicabtagene ciloleucel as standard of care therapy after 2 or more lines of therapy. Tumor metabolic volume (TMV) and mean standard uptake value (SUVmean) of various organs were quantified using ROVER [Region of interest (ROI) visualization, evolution, and image registration] software (ABX advanced biochemical compounds GmbH, Radeberg, Germany). Statistical analysis was completed using STATA 14 (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). All tests were performed after testing the normality distribution assumption. Temporal changes were assessed using paired t-tests, and between-group analyses were completed with two-sample t-tests. Results: SUVmean increased significantly after CAR-T therapy in the following organs (D+30 v baseline pre-CAR-T PET/CT): cerebral cortex (8.23 v 7.09, p=0.036), cerebellum (6.26 v 5.56, p=0.024), basal ganglia (9.22 v 7.61, p=0.005), parotid gland (1.61 v 1.42, p=0.004), liver (2.47 v 2.17, p=0.002), spleen (2.08 v 1.84, p=0.043), and pancreas (1.76 v 1.48, p

Description: Introduction : With increased use of CAR-T for relapsed/refractory (R/R) large B-cell lymphoma (LBCL), CAR-T related complications including cytokine release syndrome (CRS) and ICANS pose a significant clinical challenge. While CAR-T mediated inflammation leading to endothelial activation and blood-brain barrier disruption may play a key role in ICANS, the exact mechanism remains unclear. Prognostic or predictive biomarkers for ICANS are not well established. Recent reports (Karschnia et al, Blood 2019) suggested an association between ICANS and inferior overall survival (OS). To better understand ICANS, we herein report a single-center analysis of LBCL patients treated with CD19-directed CAR-T, exploring the associated clinical features, predictive biomarkers, and its prognostic significance. Methods: Patients (pts) with R/R LBCL treated with axicabtagene ciloleucel (Axi-cel) between 4/2018-5/2019 were identified. Data regarding patient and disease characteristics, treatment course, and clinical outcomes was collected (Table 1). Laboratory variables were collected at time of mononuclear cell harvest, day of initiation of lymphodepletive therapy, and day of CAR-T infusion (D0). CRS and ICANS were graded per the Lee and CTCAE v4.03 criteria, respectively. Time to progression (TTP) and OS were estimated by the Kaplan-Meier method and groups compared with the logrank test. Cox Proportional Hazard Model was applied for prognostic modeling. Binary logistic regression was used for multivariable analysis of patient characteristics at D0 associated with ICANS. Results: Forty-five pts with R/R LBCL (35 DLBCL, 7 TFL, 3 PMBCL) treated with Axi-cel were identified (Table 1). Twenty-five pts developed ICANS: n=7 with Grade (Gr) I-II, n=18 with Gr III-IV. Most common initial ICANS symptoms were dysgraphia, confusion, and somnolence; median time to ICANS was 5 days (range 3-11 days). Acute abnormalities were seen on brain MRI in 7 (28%) ICANS pts; EEG done in 10 ICANS pts showed diffuse slowing in all pts and focal slowing in 3 pts. All ICANS pts had preceding CRS, treated with tocilizumab (n=25, median 2.5 doses) and siltuximab (n=2). Twenty-three (92%) pts with ICANS required steroid therapy, with a median total dose equivalent to 221 mg of dexamethasone for a median duration of 12.5 days. Two pts exhibited protracted neurotoxicity manifested by short-term memory loss and profound weakness with immobility. Twenty-two (49%, 95% CI 34-64%) pts achieved CR, 16 PR, and 5 PD. At time of analysis, n=18 had disease relapse/progression and n=35 were alive. Censoring pts that progressed, the median observation time for TTP was 9.3 months. Censoring pts who died, the median observation time for OS was 7.9 months. At 9 months OS (±1 SE) was 76.1%±7.4%, and 56.0%±8.0% were progression-free. Logistic regression showed increasing fibrinogen level at D0 was associated with increasing risk of ICANS (p=0.003) and specifically, Gr III-IV ICANS [p

Description: Introduction Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a powerful therapy for relapsed and refractory (R/R) B-cell malignancies. A growing body of research suggests that CAR-T therapy can be safe and effective in patients who have previously received allogeneic hematopoietic stem cell transplantation (alloHSCT). "Pseudo-allogeneic" CAR-T therapy refers to manufacture of engineered T-cells collected from an alloHSCT recipient exhibiting 100% donor chimerism. This CAR-T approach poses theoretical risks due to alloreactivity and increased CAR-T toxicity. Most studies to date in this area have enrolled patients with leukemia. We present here a single-center experience with pseudo-allogeneic CAR-T following alloHSCT in 6 patients with large B-cell lymphoma (LBCL). Patients and Methods Patients with R/R LBCL who underwent treatment with axicabtagene ciloleucel (axi-cel) CAR-T after prior alloHSCT were identified. All patients underwent lymphodepletion with cyclophosphamide and fludarabine prior to CAR-T infusion. CAR-T toxicities, namely cytokine release syndrome (CRS) and immune effector-cell associated neurotoxicity syndrome (ICANS) were graded in accordance with the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Results Six patients who underwent axi-cel CAR-T due to post-alloHSCT R/R LBCL were identified. All patients had stage ≥II disease. At the time of CAR-T apheresis, all patients had ≥95% donor chimerism and were off immunosuppression, without evidence of GVHD. Manufacturing failure occurred in only one patient (case 2) due to low viability and upon second apheresis, manufacture was successful. All 6 pseudo-allogeneic CAR-T therapy patients tolerated infusion and did not show increased incidence or severity of CRS or ICANS compared to our center's experience with standard CAR-T patients, with only one patient experiencing greater than grade 2 toxicity. Three of six patients developed graft-versus-host disease (GVHD); however, one case was in the setting of PD-1 blockade and two were isolated cutaneous manifestations. There was no incidence of severe GVHD. All three cases of GVHD underwent CAR-T within ten months after alloHSCT, whereas the three patients without GVHD were 〉1 year post-HSCT at time of CAR-T. Two cases who had donor lymphocyte infusions prior to CAR-T did not develop GVHD. In terms of efficacy, three patients achieved a complete remission. There was no perceptible relationship between the development of GVHD and the response to CAR-T. Four of six had cytopenias at day 30 after CAR-T, with only two exhibiting persistent cytopenias at day 90. Lastly, in this small sample size, no differences were seen in incidence of GVHD or treatment response between haploidentical, matched-related, and matched-unrelated alloHSCT donors. Conclusion In our experience, pseudo-allogeneic CAR-T therapy following alloHSCT appears to be a safe and well-tolerated treatment modality for R/R B-cell lymphoma. The efficacy of this modality will need to be borne out in further studies. Disclosures No relevant conflicts of interest to declare.

Description: Introduction:Chimeric antigen receptor T-cell (CAR-T) therapy has become an important treatment modality for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). However, many of these patients have aggressive disease and require a form of bridging therapy (BT) for disease control during CAR-T manufacturing. There is limited data in the literature on the most appropriate form of BT and the impact of BT on clinical outcomes. Methods:We retrospectively analyzed data on 75 patients that received CAR-T therapy at our institution. BT was defined as therapy administered between apheresis and CAR-T infusion. 52 patients received bridging therapy (BT) and 23 did not receive BT (NBT). BT included 10 high dose (HD) steroids, 28 chemotherapy-based regimen (CT), and 14 radiation therapy (RT). CT included cytotoxic chemotherapy, immunotherapy, and targeted therapy. IRB approval was obtained for this study. Statistical analysis was conducted with SAS v9.4. Univariate analysis Cox proportional hazard model was used and p-values for response rate were generated from Fisher's exact test. The methods of generalized linear model and logistic regression were used to associate the toxicity grades and cytopenias with BT, respectively. Results:Many patient and disease characteristics between BT and NBT groups were similar, with minor, non-statistically significant differences (See Fig. 1a). Although while the incidence of stage III/IV patients in the BT and NBT group was comparable (p=0.79), in subgroup analysis, there were significantly more stage III/IV patients in the CT subgroup and NBT than in the RT and HD steroids subgroups (p=0.03). There was a higher incidence of bulky disease (≥10cm) in the BT and all BT subgroups versus (vs) NBT, although this was not significant (p=0.58 and p=0.92). The number of prior lines of therapy was comparable between the BT and NBT groups (p=0.99). However, in subgroup analysis there were significantly more patients in the CT subgroup and NBT that received ≥4 lines of therapy compared with RT and HD steroids subgroups (p=0.02). There was no significant difference in overall response rate (ORR) at last follow up between BT vs NBT and BT subgroups vs NBT with approximately 50% being in complete remission in all cases (p=0.48 and p=0.54). Progression free survival (PFS) and overall survival (OS) were similar in the BT vs NBT (one-year rates of 67% vs 64% and 83% vs 75%, respectively) and this was not statistically significant (p=0.52 and 0.89), see Fig. 1b and 1c. In subgroup analysis PFS was comparable in the BT subgroups (CT 69% and HD steroids 68%) vs NBT group (67%) while RT was lower (51%), although this was not statistically significant (p=0.54). In subgroup analysis OS was slightly worse in the BT subgroups (CT 77%, RT 76%, and HD steroids 72%) vs NBT group (83%) although was not statistically significant (p=0.93). The development of cytokine release syndrome (CRS) was comparable in the BT vs NBT group and in BT subgroups vs NBT (p=0.18 and p=0.53). The median grade of immune effector cell-associated neurotoxicity syndrome (ICANS) was higher in BT than NBT (grade 2 vs 0) and trended towards statistical significance (p=0.09). The development of cytopenias at day +180 following CAR-T therapy was significantly higher in BT (50%) vs NBT (13.3%) and was statistically significant (p= 0.038). Subgroup analysis also showed significantly increased cytopenias at day +180 in CT (58.3%) and RT (57.1%) subgroups (p= 0.04). Conclusion:In our single-institution experience, BT prior to CAR-T therapy is feasible and may preserve CAR-T candidacy in patients with rapidly progressive LBCL. BT does not appear to significantly affect ORR, PFS, and OS. The incidence of CRS was comparable, although there was a higher incidence of ICANS in BT, which trended towards significance, and could be contributed to higher tumor bulk in the BT group. BT patients receiving CT and RT for BT were more likely to experience prolonged cytopenias, likely due to the myelosuppressive impact of BT and previous lines of chemo-immunotherapy agents. In conclusion, in high-risk patients with advanced and/or aggressive disease, BT may provide disease stabilization to CAR-T with a similar toxicity profile compared to NBT patients, although BT patients are more likely to experience prolonged cytopenias after CAR-T therapy. Disclosures Kansagra: Alnylam Pharmaceuticals, Bristol Myers Squibb /Celgene, GlaxoSmithKline, Janssen, Pharmacyclics, Takeda Pharmaceuticals, Pfizer, Karyopharm Therpeutics:Other: Advisory Board.Hardy:Incyte Corporation:Other: Advisory Board Member;American Gene Technologies:Other: DSMB Member;Kite/Gilead:Other: Advisory Board Member.

Description: The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p 〈 0.001), higher hemoglobin, (p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p 〈 0.001), and the bcr3 isoform (p 〈 0.001). FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p 〈 0.001). High FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 109/L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8–57.2; p 〈 0.001). Our results provide additional evidence that FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.