e18535 Background: Acute myeloid leukemia (AML) predominantly affects elderly patients. Standard of care treatment includes induction chemotherapy, followed by consolidation with 4 cycles of high dose cytarabine (HiDAC) at 3gm/m2 with or without allogeneic stem cell transplantation (alloSCT). HiDAC dose was established based on CALGB 8525, which showed an improved leukemia-free survival compared to lower doses cytarabine. Older patients did not have the same benefit due to increased mortality and neurotoxicity. There has not been a formal study of ideal dosing of consolidation for older patients. Our institution has utilized an approach for reducing the dose of HiDAC for patients aged ≥60. Methods: We conducted a retrospective analysis of AML patients aged ≥60 treated with Ara-C consolidation at UPMC between January 1, 2004 and September 19, 2022. We described the dosing characteristics and incidence of neurotoxicity of patients who received at least one full cycle of consolidation Ara-C (6 doses total given on days 1,3,5). We evaluated the association between Ara-C dose, number of completed cycles, overall survival (OS) and relapse free survival (RFS). Results: 156 patients ≥60 years were included (median, 66.1 years; range, 59.6-78.3). Neurotoxicity was observed in 3 patients; after the 1 st cycle at 2gm/m2, 1 st cycle at 1gm/m2 and 2 nd cycle at 2gm/m2 respectively. Median Ara-C dose per cycle was 1.5 gm/m2 (range, 1.0-3.0). 41% of patients received a median dose ≥2gm/m2 per cycle. Over half of patients (58%) completed 4 cycles; 43% of these patients received a median dose ≥2gm/m2 per cycle. Among all patients, the most common reasons for discontinuation were progression (24 patients, 17%) and alloSCT (8 patients, 5%). Median OS for the entire cohort was 1.8 years. 26 patients (16.8%) received alloSCT. Number of cycles completed correlated with improved OS (p<0.001). Among patients who completed 4 cycles, median OS was 4.8 years (95% CI 1.8-NR) in those who received Ara-C at a dose of ≥2gm/m2 versus 2.7 years (95% CI 1.9, 5.3) in those who received Ara-C at <2gm/m2. The hazard ratio (HR) for OS with ≥2gm/m2 at 4 cycles was 0.5 (95% CI 0.3-0.9; p=0.02). In the group of patients who received 4 cycles median RFS was 1.71 years (95% CI 1.29-5.18) at ≥2gm/m2 versus 1.56 years (95% CI 1.28-2.37 ) at <2gm/m2. HR was 0.7 (95% CI 0.4-1.1; p=0.16). Conclusions: Cytarabine consolidation in patients ≥60 years with AML is safe and feasible. Neurotoxicity was rare, especially at reduced dose. We observed improved OS after completing the full 4-cycle Ara-C consolidation regimen. Similarly, there were improved outcomes with median Ara-C dose ≥2gm/m2 per cycle for those who received 4 cycles. RFS was not statistically different in our limited sample which might be suggestive of a similar leukemia-free survival at both higher and lower dose of Ara-C. We plan to further analyze the characteristics of patients who derived most benefit from higher dose of Ara-C.

Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m2 continuous IV infusion for 5 days. Forty-four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4- and 8-week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first-line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.

Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission.

Konstantinos Lontos , Anastasia Tsagianni, Mounzer Agha, Anastasios Raptis, Jing-Zhou Hou, Rafic Farah, Robert L. Redner, Annie Im, Kathleen A. Dorritie, Alison Sehgal , James Rossetti, Nidhi Aggarwal, Melissa Saul, Michael Boyiadzis and Nathanael G. Bailey UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study.

BACKGROUND:Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal B-cell lymphoma, which has traditionally been associated with poor outcomes. Despite increasing recognition, IVLBCL requires a high degree of clinical suspicion on the part of the clinician for its diagnosis.CASE SERIES:We present four patient cases: A 69-year-old female with constitutional symptoms and cognitive decline; a 78-year-old female with kidney injury and constitutional symptoms whose disease rapidly progressed to multiorgan failure and death; a 70-year-old asymptomatic female with an incidentally found, enlarged thyroid; and a 63-year-old male with cytopenia and constitutional symptoms. Retrospective chart analysis was performed on these four patients diagnosed with IVLBCL at our Institute to identify the pathognomonic features of the disease and compare these to the published evidence. IVLBCL has a heterogeneous presentation, as seen in our four patients. The disease is characterized by the exclusive presence of malignant cells inside the blood vessels and lack of organ infiltration. Traditional preliminary diagnostic modalities such as imaging are usually inconclusive, given the paucity of lymphomatous aggregates. A bone marrow biopsy, random skin biopsies, or a focal organ biopsy in appropriate cases is required for diagnosis. Immunosuppression might play a role in the pathogenesis. Timely initiation of aggressive cancer-directed therapy was associated with improved outcomes. Monitoring for disease response and relapse continues to be a challenge.CONCLUSION:Our mini-series highlights the significance of timely diagnosis and intervention in IVLBCL and emphasizes the importance of further research to determine its association with immunosuppression.

Konstantinos Lontos ‡ , Anastasia Tsagianni , Mounzer Agha, Anastasios Raptis, Jing-Zhou Hou, Rafic Farah, Robert L. Redner, Annie Im, Kathleen A. Dorritie, Alison Sehgal , James Rossetti, Nidhi Aggarwal, Melissa Saul, William Gooding and Michael Boyiadzis UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Biostatistics Facility, UPMC Hillman Cancer Center, Pittsburgh, PA, USA

Background Acute myeloid leukemia (AML) is a disease characterized by a clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elements. The standard treatment for newly diagnosed AML has not changed appreciably over the last few decades and consists primarily of an anthracycline combined with a nucleoside analogue. Complete remission (CR) rates of 65-80% can be expected in younger patients but decrease with older age. There is no agreed standard of care for AML patients that do not respond to initial first line induction therapy. Although remission after second-line therapy may occur, the CR rate is lower. A few chemotherapy regimens have been used in patients with resistant disease with overall CR rates of 20-40%. Gemtuzumab ozogamicin (GO) is an antibody drug conjugate consisting of a recombinant humanized antibody to CD33 which is linked to calicheamicin. Although GO is currently approved for induction therapy in combination with "7+3", its benefit is mostly evident in favorable risk disease (Hills et al Lancet Onc 2014) and thus its use is mostly limited in this setting. Pre-clinical data suggest that GO is most effective when it saturates CD33 which happens in low-burden disease (Van der Velden et al Leukemia 2004). Thus, we decided to proceed with a trial that incorporates gemtuzumab ozogamicin on the 2nd induction regimen for patients that did not achieve complete remission with the first. Methods This is a phase II, singe-center clinical trial of GO in combination with mitoxantrone and etoposide in patients with AML that persisted after their 1st induction regimen. The patients are eligible if they have at least 10% of blasts in their day 14 bone marrow biopsy and CD33 expression in at least 30% of leukemic blasts in the bone marrow. Patients with repeat bone marrows after day 14 showing progression of AML (>5% blasts) were also eligible. Patients also need to have ECOG performance status 0-2, left ventricular ejection fraction (LVEF) >50%, GFR > 30 ml/min, AST/ALT < 2.5 x upper normal limits and total bilirubin <2 x upper normal limit. Patients that received CPX-531 for induction are excluded due to concerns for prolonged thrombocytopenia. The standard of care for our center for this patient population is 10mg/m2 of mitoxantrone on days 1-5 and 100mg/m2 of etoposide on days 1-5. Trial patients receive the same regimen and a single dose of GO 3mg/m2 (capped at 4.5mg) on day 6. The primary endpoint of the trial is complete remission rate (CR). The hypothesis is that addition of GO to mitoxantrone, and etoposide will increase our historical CR rate of 35% to 50%. The trial has a Simon's two-stage design, with an interim analysis planned after 16 evaluable patients have been enrolled. The trial plans to accrue 44 evaluable patients. This design has an alpha of 0.15 and 80% power. Secondary objectives include progression-free survival, overall survival, and treatment-related mortality. To-date we have enrolled 15 patients, 13 of them evaluable. 2 patients died from sepsis before the administration of GO. We have not recorded any episodes of VOD so far. Recruitment is continuing and this trial is registered on clinicaltrials.gov; NCT03839446.

Purpose Central venous catheters (CVCs) are widely used in acute myeloid leukemia (AML) patients. Complications associated with CVCs are frequently encountered and contribute to morbidity and mortality. Prospective studies investigating and comparing complications of different types of CVCs in AML patients and their effects on the quality of life are limited. Methods We conducted a prospective observational study and evaluated the complications associated with the use of CVCs in adult AML patients during induction chemotherapy and evaluated quality of life outcomes as reported by the patients during and after their hospitalization. Results Fifty newly diagnosed patients with AML (median age, 59 years) who received intensive induction chemotherapy were enrolled in the study. Twenty-nine patients (58%) had a peripherally inserted central catheters (PICCs) placed and 21 (42%) patients received a Hickmann tunneled central catheter (TCC). Three percent of cases developed catheter-related thrombosis in PICCs and no thrombosis in TCCs. Catheter-related bloodstream infection was diagnosed in 8% of patients. CVC occlusion occurred in 44 patients (88%). The total number of occlusion events was 128; 97% of patients with PICCs and 76% of patients with TCCs ( p = 0.003). All patients reported that the use of CVC simplified their course of treatment. Most patients reported similar restrictions in activity associated with TCCs and PICCs. Conclusion The present study demonstrates that thrombosis and catheter-related bloodstream infections remain important complications of CVCs in AML patients. Occlusion rates were higher with the use of PICCs and the use of CVCs impacted the quality of life.

Allogeneic hematopoietic cell transplantation (HCT) requires a complex, multicomponent medical regimen after hospital discharge. Patients must manage multiple medications; care for their catheter; minimize exposure to sources of potential infection; follow diet, exercise, and self-care guidelines; and attend frequent follow-up medical appointments. Their caregivers are tasked with helping them manage the regimen. Despite the importance of this management in preventing adverse clinical outcomes, there has been little study of regimen nonadherence and its predictors. We sought to prospectively determine rates and predictors of nonadherence to components of the post-HCT medical regimen during the first 8 weeks after hospital discharge. Patients (n = 92) and their caregivers (n = 91) (total n = 183) completed interview assessments pre-HCT, and at 4 weeks and 8 weeks after hospital discharge post-HCT. Sociodemographic factors (eg, age, sex), patient clinical status (eg, disease type, donor type), patient and caregiver self-reported health-related factors (eg, medical comorbidities), and patient and caregiver psychosocial factors (eg, anxiety, depression, HCT task-specific and general self-efficacy, relationship quality) were assessed pre-HCT. Nonadherence to each of 17 regimen tasks was assessed at 4 and 8 weeks after hospital discharge via self and caregiver collateral reports. Nonadherence rates varied among tasks, with 11.2% to 15.7% of the sample reporting nonadherence to immunosuppressant medication, 34.8% to 38.6% to other types of medications, 14.6% to 67.4% to required infection precautions, and 27.0% to 68.5% to lifestyle-related behaviors (eg, diet/ exercise). Nonadherence rates were generally stable but worsened over time for lifestyle-related behaviors. The most consistent nonadherence predictors were patient and caregiver pre-HCT perceptions of lower Fla task efficacy. Higher caregiver depression, caregiver perceptions of poorer relationship with the patient, having a nonspousal caregiver, and having diseases other than acute myelogenous leukemia also predicted greater nonadherence in 1 or more areas. Rates of nonadherence varied across tasks, and both patient and caregiver factors, particularly self-efficacy, predicted nonadherence. The findings highlight the importance of considering not only patient factors, but also caregiver factors, in post-HCT regimen nonadherence. (C) 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

8048 Background: Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that leverages aminopeptidases and rapidly releases alkylating agents inside tumor cells. Melflufen has a mechanism of action distinct from other alkylating agents (Slipicevic et al. AACR 2020. Abs. 1843). In the O-12-M1 (NCT01897714) and HORIZON (OP-106; NCT02963493) studies, melflufen plus dex showed meaningful efficacy and a clinically manageable safety profile in pts with RRMM (Richardson et al. Lancet Haematol. 2020;7:5; Richardson et al. J Clin Oncol. 2020;Dec 9 [Epub]). This pooled analysis examines pts from these studies exposed to prior alkylators. Methods: Both the O-12-M1 and HORIZON studies included pts with RRMM who received ≥ 2 prior lines of therapy (LoTs) and had a primary endpoint of overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) and safety. Data from the 2 studies were pooled and analyzed according to previous exposure and refractoriness to alkylators before study entry. Refractoriness to prior alkylator therapy was defined as disease that failed to achieve a minimal response or progressed while on therapy, or within 60 d of last therapy. Results: Of 202 pts (HORIZON: n = 157, cutoff January 14, 2020; O-12-M1: n = 45, cutoff October 29, 2019), 178 (88%) had been exposed to alkylators in ≥ 1 prior LoT (see Table for subgroups). Pts exposed and refractory to alkylators in ≥ 2 LoTs had the highest number of pts refractory to an alkylator in the last LoT (61%), and 82% were refractory to an alkylator within 12 mo of study entry. Meaningful response rates were seen in all subgroups, except for pts who were exposed and refractory to alkylators in ≥ 2 prior LoTs (see Table). PFS trended toward being shorter with higher exposure and refractoriness to prior alkylators. Results should be interpreted with caution due to limited pt numbers. Grade 3/4 adverse events (AEs) were similar between pts exposed to prior alkylators (O-12-M1: 85%; HORIZON: 89%) and the overall population (O-12-M1: 84%; HORIZON: 89%). The most common AEs were hematologic, but were mostly reversible and clinically manageable. Nonhematologic AEs were infrequent and primarily grade 1/2. Conclusions: Melflufen in combination with dex showed meaningful efficacy and a clinically manageable safety profile in pts with RRMM exposed/refractory to prior alkylators. Clinical trial information: NCT02963493 and NCT01897714. [Table: see text]

Relapsed/refractory multiple myeloma (RRMM) is known to have a high burden of disease and complications associated with refractoriness to prior lines of therapy. Severe pain and fatigue symptoms and impairments in physical and emotional functioning have been strongly linked to reduced health-related quality of life (HRQoL) in patients with RRMM. Assessment of patient reported-outcome measures from the pivotal, Phase II HORIZON study (OP-106; NCT02963493) in patients with RRMM (n = 64) demonstrated that melphalan flufenamide (melflufen) plus dexamethasone treatment preserved HRQoL. Patients had clinically meaningful improvements, even after eight treatment cycles, in relevant scales such as global health status/QoL, physical functioning, emotional functioning, pain, and fatigue. Patients with triple-class-refractory disease (n = 50) displayed similar improvements. Patient-reported outcome deterioration was delayed for a substantial amount of time in patients who experienced a response to melflufen plus dexamethasone treatment relative to patients who did not experience a response. These findings support the notion that treatment with melflufen plus dexamethasone may sustain or improve HRQoL over time in patients with RRMM, including in patients with triple-class-refractory disease for whom outcomes are generally worse. The clinical benefits observed in patients from the HORIZON trial are encouraging and supportive of translation into real-world practice.

Background: EMD is characterized by a subclone of aggressive MM cells that thrive and grow independent of the bone marrow microenvironment and is often associated with poor-risk features including high-risk cytogenetics, increased proliferation, evasion of apoptosis, and resistance to therapies in MM (Bladé et al. J Clin Oncol. 2011;29:3805; Deng et al. Clin Lymphoma Myeloma Leuk. 2015;15:286). Prognosis for pts with EMD is poor, particularly in the RRMM setting. Additionally, prognosis is usually poorer for pts with hematogenous-spread soft-tissue plasmacytomas than for those with bone-related plasmacytomas (Gagelmann et al. Haematologica. 2018;103:890; Mangiacavalli et al. Ann Hematol. 2017;96:73). No standard therapy has been established for this high-unmet need population (Usmani et al. Blood. 2016;128:37; Jimenez-Segura et al. Eur J Haematol. 2019;102:389), and outcomes are considerably worse than those for pts without EMD; for example, a recent analysis of isatuximab + pomalidomide + dex showed a median progression free survival (PFS) of 4.6 mo vs 11.5 mo in the total population (Beksac et al. EHA 2020. Abs. EP978). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. In the phase 2 HORIZON study (OP-106; NCT02963493), melflufen + dex showed clinically meaningful efficacy (overall response rate [ORR], 29%; median PFS, 4.2 mo; median overall survival [OS], 11.6 mo) and a manageable safety profile in pts with heavily pretreated RRMM, including in pts with triple-class-refractory MM (Richardson et al. EHA 2020. Abs. EP945). This analysis presents additional data for the largest cohort of pts with EMD in a clinical trial setting to date. Methods: Pts with RRMM must have received ≥2 lines of prior therapy, including an IMiD and a proteasome inhibitor, and been refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. Pts received melflufen 40 mg (intravenous; d1 of each 28-d cycle) and dex 40 mg/wk until progressive disease or unacceptable toxicity. The primary endpoint was ORR (≥ partial response [PR]; investigator-assessed per International Myeloma Working Group [IMWG] criteria). Secondary endpoints included PFS, OS, duration of response (DOR), and safety. For pts with known or suspected EMD, defined as either isolated soft-tissue and/or bone-related extramedullary plasmacytomas with soft-tissue extension, an assessment was required at screening and to confirm a response per IMWG criteria. Results: Of 157 pts enrolled and treated (data cutoff date, Jan 14, 2020), 55 (35%) had EMD (49% soft-tissue and 51% bone-related soft-tissue plasmacytoma). In pts with EMD, median age was 64 y (range, 43-82); median time since diagnosis was 5.6 y (range, 0.7-14.5); 35% had high-risk cytogenetics; 33% had International Staging System stage 3; median prior lines of therapy was 5 (range, 2-12); 60% had disease that was refractory to prior alkylator therapy; and 91% had triple-class-refractory MM. ORR (95% CI) was 24% (13-37) in pts with EMD and 29% (22-37) overall (N=157). In pts with EMD and the overall population, respectively, median (95% CI) DOR was 5.5 mo (1.8-not evaluable [NE]) and 5.5 mo (3.9-7.6), PFS was 2.9 mo (2.0-3.8) and 4.2 mo (3.4-4.9), and median OS was 6.5 mo (5.1-9.7) and 11.6 mo (9.3-15.4;) (Table). In pts with EMD who achieved ≥PR (n=13), median (95% CI) PFS was 17.3 mo (5.3-NE), and OS was 18.5 mo (8.7-NE). Due to low event numbers, the results in pts with ≥PR may be overestimated. The safety profile of melflufen + dex in pts with EMD was consistent with that in the overall population, with grade 3/4 treatment-emergent adverse events (TEAEs) reported in 78% and 89% of pts, respectively. In pts with EMD, the most common grade 3/4 TEAEs were anemia (42%), thrombocytopenia (40%), and neutropenia (38%); the most common nonhematologic grade 3/4 TEAE of interest was pneumonia (9%). No treatment-related deaths with melflufen + dex were reported. Conclusions: Melflufen + dex showed activity in advanced RRMM with EMD, with encouraging PFS and OS in pts with confirmed stable disease or better. The safety profile of melflufen + dex was consistent with previous reports. To date, this clinical study provides the largest cohort of pts with EMD demonstrating benefit in this population with a high unmet medical need. These data support further evaluation of melflufen + dex in RRMM with EMD. Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Mateos:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: 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; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol:Janssen: Consultancy; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Larocca:Amgen: Honoraria; Bristol-Myers Squibb: 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; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Cavo:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rodríguez-Otero:Abbvie: Consultancy; Oncopeptides: Consultancy; Medscape: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Honoraria; GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company; Kite: Consultancy; Sanofi: Consultancy. Leleu:AbbVie: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Amgen: Honoraria; Novartis: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria. Nadeem:Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Adaptive: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Hassoun:Takeda: Research Funding; Celgene: Research Funding; Novartis: Consultancy. Touzeau:Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Sanofi: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Amgen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; GlaxoSmithKline: Honoraria, Research Funding. Amor:GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Maisel:Texas Oncology: Current Employment; Amgen: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Texas Oncology: Current Employment; Kite: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Mazumder:Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; The Oncology Institute: Current Employment. Raptis:UPMC: Current Employment; INTEGRA: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Puig:THE BINDING SITE: Consultancy, Honoraria; TAKEDA: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; JANSSEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; BRISTOL-MYERS SQUIBB: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; CELGENE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; AMGEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding. Zamagni:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Takeda: Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Thuresson:Oncopeptides: Consultancy, Current equity holder in publicly-traded company; Statisticon: Current Employment. Harmenberg:Ultupharma AB: Current equity holder in private company; Medivir AB: Current equity holder in publicly-traded company; Oncopeptides AB: Consultancy, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Harlin:Oncopeptides AB: Consultancy, Current equity holder in publicly-traded company. Blade Creixenti:Takeda: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: This is a phase 2 investigational study of melflufen in RRMM.

Background: In patients with relapsed/refractory multiple myeloma (RRMM), 29%-59% have high-risk (HR) cytogenetic abnormalities that are associated with poor treatment outcomes (Kumar et al. Leukemia. 2017;31:2443; Gandhi et al. Leukemia. 2019;33:2266). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen plus dexamethasone (dex) showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated and poor-risk RRMM in the phase 2 HORIZON study (OP-106; NCT02963493; Richardson et al. EHA 2020. Abs. EP945). The overall response rate (ORR) was 29%, median progression-free survival (PFS) was 4.2 months, and median overall survival (OS) was 11.6 months. The most common nonhematologic grade 3/4 adverse event (AE) was pneumonia (10%). This is an analysis of the cytogenetic profile and a comparison of the efficacy for patients with and without HR cytogenetic abnormalities in the HORIZON study. Methods: Patients with RRMM had received ≥2 lines of prior therapy, including an IMiD and a proteasome inhibitor, and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. Patients received melflufen 40 mg (intravenously on day 1 of each 28-day cycle) and dex 40 mg/wk until progressive disease or unacceptable toxicity. The primary endpoint was ORR (≥ partial response [PR]; investigator-assessed per International Myeloma Working Group criteria); secondary endpoints included PFS, OS, duration of response (DOR), and safety. At screening, cytogenetics were evaluated using plasma cells from bone marrow aspirate by interphase fluorescence in situ hybridization and by conventional karyotyping. HR cytogenetic abnormalities were classified by the presence of t(4;14), t(14;16), t(14;20), del(17/17p), or gain(1q) (Sonneveld et al. Blood. 2016;127:2955). Results: Of the 157 patients enrolled and treated (data cutoff date, January 14, 2020), 59 (38%) had HR cytogenetic abnormalities at screening. Cytogenetic status was missing/unknown in 31 patients (20%). Among patients with HR cytogenetics, gain(1q) was seen in 41 (69%), del(17p) in 31%, t(4:14) in 31%, t(14:16) in 7%, and t(14:20) in none. Although baseline characteristics were generally similar between patients with and without HR cytogenetics (Table), fewer patients with HR cytogenetics had triple-class-refractory MM (69%) than those without HR cytogenetics (80%). The ORR (95% CI) was 20% (11-33) in patients with HR cytogenetics and 35% (25-45) in patients without HR cytogenetics. Among responding patients with HR cytogenetics (n=12), 4 achieved a very good PR and 8 a PR, with a median DOR of 6.7 months (95% CI, 3.0-not evaluable). Median DOR was 5.1 months (95% CI, 3.9-7.5) in patients without HR cytogenetics (n=34). Median PFS was 3.1 months (95% CI, 2.1-5.4) and 4.4 months (95% CI, 3.8-5.1), respectively, and OS was 11.5 months (95% CI, 8.5-13.6) and 13.2 months (95% CI, 8.1-17.6), respectively, in patients with and without HR cytogenetics. Among patients with HR cytogenetics, the ORR was 24% (95% CI, 11-40) in patients with 1 HR cytogenetic abnormality (n=38) and 14% (95% CI, 3-36) in patients with ≥2 HR cytogenetic abnormalities (n=21). Median PFS was 2.9 months (95% CI, 1.9-7.6) and 4.4 months (95% CI, 1.9-6.5), and OS was 11.6 months (95% CI, 7.7-21.1) and 11.5 months (95% CI, 4.5-13.9) in patients with 1 and ≥2 HR cytogenetic abnormalities, respectively. In patients with HR cytogenetics (n=59) and the overall population (N=157), grade 3/4 AEs were reported in 92% and 89%, respectively; the most common grade 3/4 AEs were thrombocytopenia (51% and 57%), neutropenia (47% and 53%), and anemia (36% and 43%); the most common nonhematologic grade 3/4 AE was pneumonia (17% and 10%). Serious AEs occurred in 54% of patients with HR cytogenetics and in 49% of patients in the overall population, most commonly pneumonia (17% and 9%, respectively). Conclusions: In the HORIZON study, melflufen plus dex also showed efficacy in patients with HR cytogenetics. The safety profile of melflufen plus dex in patients with HR cytogenetics was consistent with that of the overall population. Taken together, these data support further evaluation of melflufen plus dex in RRMM with HR cytogenetics. Disclosures Mateos: GlaxoSmithKline: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol:Janssen: Consultancy; Amgen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Larocca:Amgen: Honoraria; Bristol-Myers Squibb: 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; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Blade Creixenti:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Cavo:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodríguez-Otero:Kite: Consultancy; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Sanofi: Consultancy; Abbvie: Consultancy; Medscape: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene/Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company; Oncopeptides: Consultancy. Leleu:BMS-celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; GSK: Honoraria; AbbVie: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; Novartis: Honoraria. Nadeem:Adaptive: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Hassoun:Takeda: Research Funding; Celgene: Research Funding; Novartis: Consultancy. Touzeau:Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Sanofi: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. Amor:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Maisel:Texas Oncology: Current Employment; Texas Oncology: Current Employment; Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau. Mazumder:Takeda: Honoraria, Speakers Bureau; The Oncology Institute: Current Employment; Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Raptis:INTEGRA: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; UPMC: Current Employment. Puig:CELGENE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; AMGEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; JANSSEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; THE BINDING SITE: Consultancy, Honoraria; TAKEDA: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; BRISTOL-MYERS SQUIBB: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau. Harmenberg:Oncopeptides AB: Consultancy, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Medivir AB: Current equity holder in publicly-traded company; Ultupharma AB: Current equity holder in private company. Gustavsson:Vinnova: Honoraria; XSpray AB: Divested equity in a private or publicly-traded company in the past 24 months; Celgene: Divested equity in a private or publicly-traded company in the past 24 months; Bristol-Myers Squibb: Divested equity in a private or publicly-traded company in the past 24 months; Sangus Jazz AB: Current equity holder in private company; PiezoMotor AB: Current equity holder in publicly-traded company; Episurf AB: Current equity holder in publicly-traded company; Nanexa AB: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides AB: Current Employment, Current equity holder in publicly-traded company. Thuresson:Oncopeptides: Consultancy, Current equity holder in publicly-traded company; Statisticon: Current Employment. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. OffLabel Disclosure: This is a phase 2 investigational study of melflufe in RRMM.

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

Background: Pts with RRMM are a very sick population due to disease symptoms, comorbidities, side effects from treatments, and age-related fragility (Chim et al. Leukemia. 2018;32:252). Pts often experience adverse events (AEs) that affect their quality of life and reduce treatment compliance; hematologic AEs are frequent. Inpatient services for the management of AEs are often necessary and a major cost driver, with costs rising per AE episode (highest for hematologic AEs; Felber et al. ASH 2019. Abs. 4725). Additionally, a real-world study suggested that >50% of pts with hematologic AEs require readmittance to the hospital after initial treatment (Yeaw et al. ISPOR 2020. Abs. PCN78). Published data to date come from real-world evidence, with limited reports from clinical trials. Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. In the pivotal, phase 2, HORIZON study (OP-106; NCT02963493), melflufen plus dex showed clinically meaningful efficacy and a safety profile consisting primarily of clinically manageable hematologic AEs in pts with heavily pretreated RRMM (Richardson et al. EHA 2020. Abs EP945). This analysis aids to further elucidate the healthcare resource utilization of pts with RRMM treated with melfulfen in a clinical trial by evaluating the impact of AEs on hospitalizations in HORIZON. Methods: Pts with RRMM who had received ≥2 lines of prior therapy, including an IMiD and a proteasome inhibitor and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody were treated with melflufen and dex as described (Richardson et al. EHA 2020. Abs EP945). Data for specific AEs potentially related to the study drugs (melflufen and/or dex; TRAEs) requiring hospitalizations >24 h were compared with all potential TRAEs and within each preferred term with >1 event reported regardless of hospitalization. AEs were classified as TRAE if reported as related or possibly related to either study drug by the treating physician. Results: At the data cutoff date (14 Jan 2020), 157 pts were enrolled and had received ≥1 dose of study treatment; 35 (22%) had been hospitalized due to a TRAE. Pts hospitalized due to TRAEs had a median age of 63 y (range, 43-84); 31% had International Staging System stage 3 disease; 49% had high-risk cytogenetics; and 77% had triple-class-refractory MM. In the overall population (N=157), the most frequent grade 3/4 treatment-emergent AEs (TEAEs) were thrombocytopenia (57%), neutropenia (53%), and anemia (43%). Serious AEs occurred in 49% of pts, most commonly pneumonia (9%) and febrile neutropenia (5%). Of all 3713 TEAEs, 118 (3.2%) led to hospitalization. Of 2688 TRAEs, 58 (2.2%) resulted in hospitalization. Pneumonia and febrile neutropenia TRAEs resulted in the most hospitalizations, with 11 events (78.6% of pneumonia TRAEs; 0.41% of all TRAEs) and 10 events (83.3% of febrile neutropenia TRAEs; 0.37% of all TRAEs), respectively (Table). Grade 3/4 hematologic TRAEs resulting in hospitalization included thrombocytopenia (9 hospitalizations; 1.4% of thrombocytopenia TRAEs; 0.33% of all TRAEs) and neutropenia (2 hospitalizations; 0.3% of neutropenia TRAEs; 0.07% of all TRAEs). All TRAEs that resulted in hospitalization were grade 3/4 except for 2 events (1 pyrexia [grade 1]; 1 pneumonia [grade 2]). For 3 of 9 thrombocytopenia events and 1 of 2 neutropenia events, it was unclear whether the hospitalization was >24 h; however, they were included in current analysis. Conclusion: Within this heavily pretreated pt population, most TRAEs could be managed without the need for hospitalization. Hematologic AEs were common but led to few hospitalizations overall. Although 11 cases (78.6%) of TRAEs of pneumonia required hospitalization, these events represent only 0.41% of all TRAEs, and infections are normally expected in advanced RRMM (Blimark et al. Plasma Cell Disorders. 2015;100:107). Use of inpatient services are a major driver of economic burden in RRMM and have been shown to be highly utilized in less heavily pretreated populations than HORIZON (Yeaw et al. ISPOR 2020. Abs. PCN7; Felber et al. ASH 2019. Abs. 4725). Results of this analysis suggest limited use of inpatient services for TRAEs with melflufen plus dex. Further analyses of real-world data on melflufen are warranted to confirm the results presented from this analysis. Disclosures Nadeem: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Mateos:Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: 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; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Larocca:GSK: Honoraria; Janssen: 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; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Blade Creixenti:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Rodríguez-Otero:Celgene/Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company; Oncopeptides: Consultancy; Abbvie: Consultancy; Kite: Consultancy; Medscape: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Leleu:Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Amgen: Honoraria; Novartis: Honoraria; BMS-celgene: Honoraria; AbbVie: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; Janssen: Honoraria. Hassoun:Novartis: Consultancy; Takeda: Research Funding; Celgene: Research Funding. Touzeau:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Sanofi: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Amor:GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Maisel:Texas Oncology: Current Employment; Amgen: Honoraria, Speakers Bureau; Texas Oncology: Current Employment; Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Mazumder:Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; The Oncology Institute: Current Employment. Raptis:UPMC: Current Employment; INTEGRA: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Puig:BRISTOL-MYERS SQUIBB: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; CELGENE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding, Speakers Bureau; AMGEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; THE BINDING SITE: Consultancy, Honoraria; JANSSEN: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding; TAKEDA: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Research Funding. Sandberg:Oncopeptides AB: Current Employment; Novo Nordisk AS: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Pelaez:Märsta Läkarhus AB: Ended employment in the past 24 months; Oncopeptides: Consultancy. Jaques:Pharma Biotech Consultants: Consultancy; Oncopeptides: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Pfizer: Consultancy; Morphosys AG: Consultancy; Oncopeptides: Ended employment in the past 24 months. Orre:Oncopeptides: Current Employment. Cavo:GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: This is phase 2 investigational study of melflufen in RRMM.