Abstract: Many patients with ET are resistant to or intolerant of current standards of care (SOC) - hydroxyurea (HU), interferon, anagrelide - underscoring the need for novel therapies with distinct modes of action that reduce the risk of thrombosis, improve the patient's experience and favorably alter the natural history. Lysine-specific demethylase-1 (LSD1) is an enzyme critical for the self-renewal potential of malignant cells and hematopoietic differentiation, e.g., LSD1 licenses progenitors to mature into megakaryocytes, a cell central to ET pathogenesis. Bomedemstat is an orally active LSD1 inhibitor that reduced peripheral cell counts, splenomegaly, inflammatory cytokines, mutant cell burdens and improved survival in mouse models of MPNs (Kleppe et al. 2015; Jutzi et al. 2018). IMG-7289-CTP-201 is a global, open-label, Phase 2b study of bomedemstat taken once daily for 24+ weeks in patients with ET who are resistant to or intolerant of at least one SOC treatment (NCT04254978). Key eligibility criteria include patients who require cytoreduction, a platelet count & gt;450 x 10 9/L, hemoglobin ≥10 g/dL and absolute neutrophil count ≥0.5 x 10 9/L. Key objectives are safety and response, defined as platelets ≤400 x 10 9/L without new thromboembolism or disease progression. Exploratory endpoints include durability of response, reduction in WBCs, changes in mutant allele frequencies (MAF), and symptom improvement. All patients start at a dose of 0.6 mg/kg/d that is titrated to a target platelet count of 200-400 x 10 9/L. At data cut-off (15July'21), 30 patients have enrolled. Baseline median age was 68 (42-84) years with 33% males; 77% were resistant to or intolerant of HU, 10% to anagrelide, 7% to interferon, and 3% each to busulfan and ruxolitinib. The Day 1 (washout up to 28 days) mean platelet, WBC and hemoglobin values were 876 x 10 9/L (457-2220), 9.7 x 10 9/L (4.4-30.6), and 13.0 g/dL (9.4-16.5) respectively. Among all patients, median MPN10 total symptom score (TSS) at baseline was 16 (0-74); TSS & gt;10 was observed in 63% (19/30); median 30 (11-74). Genotyping by sequencing at screening (N=32) revealed mutations in JAK2 (50%) and CALR (44%) with a wide distribution of MAFs (1-85%). All patients were wild-type at the MPL locus, two patients were "triple-negatives" and five patients had copy number neutral loss of heterozygosity. Non-driver mutations were present in 31% (10/32) including EZH2, ASXL1, SF3B1 and TP53. Median time on study is 16 weeks (0-41). Platelet count was reduced in 92% (24/26) of patients treated for more than 6 weeks with 81% (21/26) achieving a platelet count of ≤400 x 10 9/L. Of the 9/30 (30%) patients with a Day 1 WBC count ≥10 x 10 9/L, 89% (8/9) had a WBC count & lt;10 x 10 9/L while on treatment (see graphs). All patients maintained a stable hemoglobin (see graph). In patients with baseline TSS & gt;10 (19/30), at Week 12, 77% (10/13) had decreased scores and 46% (6/13) demonstrated & gt;10-point improvement. Of patients resequenced (261 genes) at Week 24 (N=6), mutant allele frequencies were stable and no new mutations were detected. Enrollment is on-going; additional clinical and genetic data will be presented. The most common (reported by & gt;15% of patients) treatment-emergent AEs deemed related were dysgeusia (40%), fatigue, thrombocytopenia (without bleeding), constipation, and diarrhea (each 17%). Six AEs ≥Grade 3 were reported in 5 patients, with 2 (dysgeusia and constipation) deemed related to bomedemstat by the Investigator. Two unrelated SAEs were reported: a lung infection and a pulmonary embolus. Four patients discontinued treatment, three due to AEs (nausea, dysgeusia x 2) and one withdrew consent on Day 1. Similar to an ongoing MF study of bomedemstat (NCT03136185), there have been no safety signals, DLTs, or deaths related to drug. At the time of data cut-off, 87% (26/30) of patients remain on study. To date, in a majority of patients who were resistant or intolerant to at least one standard of care, bomedemstat has shown to be well-tolerated, reduce platelets, improve symptoms, and moderate WBC counts while maintaining hemoglobin. For those patients treated for at least 6 weeks, 81% achieved a complete peripheral blood count remission without evidence of disease progression. The mutation burden remained stable despite high molecular risk mutations. Based on this promising data, a Phase 3 study of bomedemstat for the treatment of ET is being planned. Figure 1 Figure 1. Disclosures Ross: Bristol Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Keros Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lane: BMS: Consultancy, Research Funding; Geron: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Novartis: Consultancy. Gerds: Constellation: Consultancy; AbbVie: Consultancy; Brystol Myers Squibb: Consultancy; Sierra Oncology: Consultancy; Novartis: Consultancy; PharmaEssentia: Consultancy; Incyte: Research Funding; Constellation: Research Funding; Krtos: Research Funding; CTI Biopharma: Research Funding; Imago: Research Funding; Accutate: Research Funding. Halpern: Novartis: Research Funding; Bayer: Research Funding; Tolero Pharmaceuticals: Research Funding; Agios Pharmaceuticals: Research Funding; Abbvie: Consultancy; Gilead: Research Funding; Agios: Consultancy; Imago Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Nohla Therapeutics: Research Funding; Pfizer: Research Funding. Shortt: Amgen: Research Funding; Astex: Research Funding; BMS: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Jones: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Peppe: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Natsoulis: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Navarro: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Hong: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company; Genentech, Inc.: Ended employment in the past 24 months. Harrison: Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sierra Oncology: Honoraria; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Incyte Corporation: Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Talpaz: Imago: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Grant/research support ; Constellation: Membership on an entity's Board of Directors or advisory committees. Rienhoff: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Abstract: Ruxolitinib (Jakafi®) is the one approved therapy for myelofibrosis (MF) based on reduction of splenomegaly and symptoms but JAK inhibition has not proven to significantly modify disease progression. There remains the need for novel therapies with distinct modes of action that can improve the patient experience of MF and impact progression. Lysine-specific demethylase, LSD1, is an epigenetic enzyme critical for self-renewal of malignant myeloid cells and differentiation of myeloid progenitors. LSD1 bound to GFI1b permits maturation of progenitors to megakaryocytes and enables their normal function. IMG-7289 (bomedemstat) is an orally available LSD1 inhibitor. In mouse models of myeloproliferative neoplasms (MPN), IMG-7289 reduced elevated peripheral cell counts, spleen size, inflammatory cytokines, mutant allele frequencies, and marrow fibrosis (Jutzi et al. 2018) supporting its clinical development. IMG-7289-CTP-102 is an ongoing, multi-center, open-label study that recently transitioned from a Phase 1/2a dose-range finding study to a Phase 2b study of IMG-7289 administered orally once-daily in adult patients with intermediate-2 or high-risk MF resistant to or intolerant of ruxolitinib. The key objectives are safety, PD, changes in spleen volume (MRI/CT) and total symptoms scores (TSS) using the MPN-SAF instrument. Inclusion criteria included a platelet count ≥100K/μL. Bone marrow (BM) biopsies and imaging studies (both centrally-read) were conducted at baseline and during washout (post-Day 84). The MPN-SAF was self-administered weekly. Phase 1/2a patients were treated for 84 days followed by a washout of up to 28 days. Patients demonstrating clinical benefit could resume treatment for additional 12 week cycles. Dosing was individually tailored using platelet count as a biomarker of effective thrombopoiesis. Patients were started at a presumed sub-therapeutic dose of 0.25 mg/kg/d and up-titrated weekly until the platelet count rested between 50 and 100K/μL. This preliminary analysis includes 20 patients; 18 enrolled in the Phase 1/2a study, 2 in the Phase 2b portion. 50% had PMF, 35% Post-ET-MF, 15% Post-PV-MF. The median age was 65 (48-89) with 70% males. The median baseline platelet count was 197 k/μL (102-1309k/μL). 12 patients (56%) were transfusion-dependent at baseline. Sixty percent were IPSS-classified as high risk, the remainder, intermediate risk-2. 71% had more than 1 mutation of the 261 AML/MPN genes sequenced of which 63% were high molecular risk (ASXL1, U2AF1, SRSF2) mutations; 31% had abnormal karyotypes. Sixteen patients completed the first 12 weeks; 4 patients withdrew, one due to fatigue (Day 33), one for progressive disease (Day 39), one due to physician decision (Day 76), one for an unrelated SAE of cellulitis (Day 83). All patients were up-titrated from the starting dose 0.25 mg/kg to an average daily dose of 0.89 mg/kg ± 0.20 mg/kg, the dose needed to achieve the target platelet count range; 17 achieved the target platelet range in a mean time of 45 days. Of patients evaluable for response after cycle 1 in Phase1/2a (N=14), 50% had a reduction in spleen volume from baseline (median SVR: -14%; -2% to -30%). Further, 79% (N=11) recorded a reduction in TSS (mean change -28%; -13% to -69%); for 21% of patients (N=3), the change was & gt;-50%. Improved BM fibrosis scores at Day 84 were observed in 2/13 patients. Two patients had improvement in transfusion requirements. Plasma IL-8 levels were significantly elevated in 6/14 patients at baseline and dropped in a dose-dependent manner over 21 days in 5/6 patients. The mean duration of treatment is 166 days (14-539) at the census point in this ongoing study. Nineteen patients (95%) reported 358 AEs of which 22 were SAEs. Of the SAEs, 2 were deemed by investigators as possibly related: painful splenomegaly and heart failure. There have been no safety signals, DLTs, progression to AML, or deaths. This is the first clinical study of an LSD1 inhibitor in patients with MPNs. Once-daily IMG-7289 was well-tolerated in a heterogeneous population of patients with advanced MF and limited therapeutic options. Despite under-dosing and slow dose escalation, IMG-7289 improved symptom burdens in most patients and modestly reduced spleen volumes in a subset of patients. The Phase 2b 24-week expansion study with more aggressive dosing aimed at preserving safety and enhancing efficacy is open for enrollment in the US, UK and EU. Figure Disclosures Pettit: Samus Therapeutics: Research Funding. Gerds:Imago Biosciences: Research Funding; Celgene Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Roche: Research Funding; Sierra Oncology: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy. Yacoub:Hylapharm: Equity Ownership; Agios: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Ardelyx: Equity Ownership; Cara: Equity Ownership; Dynavax: Equity Ownership. Watts:Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bradley:AbbVie: Other: Advisory Board. Shortt:Celgene: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Astex: Research Funding; Amgen: Research Funding; Gilead: Speakers Bureau; Takeda: Speakers Bureau. Natsoulis:Imago BioSciences: Consultancy, Equity Ownership. Jones:Imago BioSciences: Employment, Equity Ownership. Talpaz:Samus Therapeutics: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Constellation: Research Funding; Imago BioSciences: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CTI BioPharma: Research Funding. Peppe:Imago BioSciences: Employment, Equity Ownership. Ross:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rienhoff:Imago Biosciences: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Abstract: There is an unmet need for novel therapies with distinct modes of action to offer clinical benefit for patients with myelofibrosis (MF) who become resistant or intolerant to JAK inhibitors. Lysine-specific demethylase-1 (LSD1) is a histone demethylase critical for self-renewal potential of malignant myeloid cells for hematopoietic differentiation, e.g., LSD1 licenses maturation of megakaryocytes, one cell type critical to the pathogenesis of MF. Bomedemstat is an orally active LSD1 inhibitor that in mouse models of MPNs reduced peripheral cell counts, splenomegaly, inflammatory cytokines, marrow fibrosis, mutant cell burden and overall survival (Jutzi et al. 2018). IMG-7289-CTP-102 is a global, open-label Phase 1/2 study evaluating bomedemstat dosed once daily in MF patients (NCT03136185). Data from this ongoing study are presented. Key eligibility criteria include IPSS int.-1 or -2 or high-risk patients refractory or resistant to, inadequately controlled by or intolerant of available approved therapy, or in the Investigator's judgment, are not candidates for available approved therapy, peripheral blast count ≤10%, absolute neutrophil count ≥0.5 x 10 9/L, and platelet count ≥100 x 10 9/L. Key objectives are safety and reduction of spleen volume (SVR) by MRI/CT and total symptoms scores (TSS) using the MPN-SAF instrument. Serial bone marrow (BM) biopsies and imaging studies are read centrally. Of 261 genes recurrently mutated in AML/MPN/MDS, germline and somatic baseline and follow-up sequencing is conducted to quantify existing or new mutant alleles frequencies (MAF). Dosing is individually tailored using platelet count as a biomarker of bomedemstat activity on megakaryocyte function, targeting a range between 50-100 x 10 9/L and titrating as needed. At data cutoff (15 July 2021), the study is fully enrolled with 89 patients: 49% primary MF, 30% post-essential thrombocythemia-MF, 21% post-polycythemia vera-MF. Median age is 68 (35-88) with 52% males. Prior treatment with ruxolitinib was reported in 81% (72/89), 43% (38/89) had also received up to 3 different treatments. 30% of patients (25/83) had received ≥1 RBC transfusion prior to dosing. By IPSS, 54% were high-risk, 40% int.-2, and 6% int.-1. At screening (N=88), sequencing to an average depth of & gt;1000, JAK2 was mutated in 70%, CALR in 22%, and MPL in 7%; 64% had ≥2 mutations of which 66% had high-molecular risk mutations in ASXL1, IDH1/2, EZH2 and/or SRSF2. The median duration of treatment is 17 weeks (2-102). Of all enrolled patients for whom data is available (evaluable) at 24 weeks for TSS with baseline value ≥20, 89% recorded a reduction in TSS (mean change -36%; -81% to 21%) with 39% reporting ≥50% reduction. Of all patients evaluable for SVR at 24 weeks (N=27), 78% had a reduction in spleen volume from baseline (mean SVR: -4%; -41% to 107%) with 37% showing ≥20% SVR. Of evaluable patients (N=29), 86% had stable (∆ & lt;±1.0 g/dL) or improved hemoglobin ( & gt;1.0 g/dL). Of patients evaluable for BM fibrosis scoring post-baseline (N=29), 17% improved by 1 grade and 66% were stable. Serially sequencing 43 patients, MAFs in one or more alleles were reduced in 42% with 1 patient in complete molecular remission, and stable in 44%. Clones with JAK2 and/or ASXL1 mutations were most frequently reduced. MAF reduction also correlated with efficacy: SV and/or TSS were improved in patients in whom MAFs were also decreased. No new mutations were identified in any patient. No patient transformed to AML during this study. The most common non-hematologic AEs reported by patients were diarrhea and dysgeusia, each at 28% (25/89). There have been 13 related SAEs with 3 Grade 2, 9 Grade 3 and 1 Grade 4 (thrombocytopenia). Thirty-nine patients remain on study. Early terminations ( & lt;24 weeks) due to AEs occurred in 13 (15%) patients with 5 related to bomedemstat, and 15 discontinued for other reasons. There have been no safety signals, DLTs, or deaths related to drug. In a patient population with advanced disease, a heavy mutation burden and limited treatment options, once-daily bomedemstat as monotherapy had an acceptable tolerability profile, relieved symptoms, reduced spleen volume and improved anemia without any significant safety signals. Additionally, reductions in the allele frequency of both driver and high molecular risk mutations were observed and correlated with improved efficacy metrics. The study is now fully enrolled and additional data will be presented. Disclosures Yacoub: Cara: Current equity holder in publicly-traded company; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dynavex: Current equity holder in publicly-traded company; Seattle Genetics: Honoraria, Speakers Bureau; Ardelyx: Current equity holder in publicly-traded company; Hylapharm: Current equity holder in publicly-traded company. Bradley: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gerds: AbbVie: Consultancy; CTI BioPharma: Research Funding; Sierra Oncology: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; PharmaEssentia Corporation: Consultancy; Constellation: Consultancy; Novartis: Consultancy. Shortt: Amgen: Research Funding; Astex: Research Funding; BMS: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Mead: Abbvie: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau. Göthert: AOP Orphan Pharmaceuticals: Honoraria, Other: Travel reimbursement; zr pharma & : Honoraria; Proteros Biostructures: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel reimbursement; Incyte: Consultancy, Honoraria, Other: Travel reimbursement; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel reimbursement. Koschmieder: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Shire: Honoraria, Other; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Abbvie: Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Image Biosciences: Other: Travel support; Alexion: Other: Travel support; CTI: Membership on an entity's Board of Directors or advisory committees, Other; Karthos: Other: Travel support; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding. Jones: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Peppe: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Natsoulis: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company. Hong: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company; Genentech, Inc.: Ended employment in the past 24 months. Harrison: BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sierra Oncology: Honoraria; Incyte Corporation: Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vannucchi: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Watts: Rafael Pharmaceuticals: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Aptevo Therapeutices: Research Funding. Ross: Keros Therapeutics: Consultancy, Honoraria; Bristol Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Talpaz: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Constellation: Membership on an entity's Board of Directors or advisory committees; Imago: Consultancy; Celgene: Consultancy; Takeda: Other: Grant/research support . Rienhoff: Imago BioSciences: Current Employment, Current equity holder in publicly-traded company.

Abstract: Older patients with acute leukemia (AL) have a high symptom burden and poor prognosis. Although integration of palliative care (PC) with oncologic care has been shown to improve quality-of-life and end-of-life care in patients with AL, the malignant hematologists at our tertiary care hospital make limited use of PC services and do so late in the disease course. Using the Plan-Do-Study-Act (PDSA) methodology, we aimed to increase early PC utilization by older patients with newly diagnosed AL. METHODS: We instituted the following standardized criteria to trigger inpatient PC consultation: (1) age 70 years and older and (2) new AL diagnosis within 8 weeks. PC consultations were tracked during sequential PDSA cycles in 2021 and compared with baseline rates in 2019. We also assessed the frequency of subsequent PC encounters in patients who received a triggered inpatient PC consult. RESULTS: The baseline PC consultation rate before our intervention was 55%. This increased to 77% and 80% during PDSA cycles 1 and 2, respectively. The median time from diagnosis to first PC consult decreased from 49 days to 7 days. Among patients who received a triggered PC consult, 43% had no subsequent inpatient or outpatient PC encounter after discharge. CONCLUSION: Although standardized PC consultation criteria led to earlier PC consultation in older patients with AL, it did not result in sustained PC follow-up throughout the disease trajectory. Future PDSA cycles will focus on identifying strategies to maintain the integration of PC with oncologic care over time, particularly in the ambulatory setting.

Abstract: Purpose: Oral mucositis (OM) is a common, debilitating complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Supersaturated calcium phosphate rinse (SCPR) and palifermin have shown efficacy in preventing severe OM. However, whether their efficacy differs is unknown. We aimed to compare the efficacy of SCPR and palifermin in HSCT patients receiving myeloablative conditioning. Methods: A comprehensive review of our institutional database was performed to identify patients who received myeloablative-conditioning therapy over 5 years. All HSCT patients who received radiotherapy-based myeloablative conditioning and received either palifermin or SCPR within the study period were included. Most patients received Fludarabine, Busulfan, and total body irradiation (FBT). Patients were divided into two groups based on the OM prophylactic agent received. The primary outcome is prevalence of severe OM (WHO Grade 3 and 4). The secondary outcomes are a prevalence of all-grade OM and WHO Grade 4 OM. These outcomes were compared between the two groups. Results: We identified 26 patients who received SCPR and 122 patients who received palifermin for OM prophylaxis. The prevalence of World Health Organization (WHO) Grade 3 or 4 OM was significantly lower in the palifermin group (57% vs. 100%, p = 0.01). In addition, the palifermin group had lower WHO Grade 4 OM (22% vs. 62%, p = 0.0006). The overall prevalence of OM was not significantly different between the two groups (86% for palifermin group vs. 100% for SCPR arm, p = 0.15). Subgroup analyses demonstrated improved outcomes with palifermin, regardless of age, sex, disease status, donor type, and primary diagnosis. Conclusion: When compared to SCPR, the use of palifermin is associated reduced severity of OM in HSCT patients receiving radiotherapy-based myeloablative conditioning.