Jani, Prachi

Abstract Background: Mosunetuzumab, a CD20xCD3 bispecific antibody, can be administered in the outpatient setting for a fixed duration. Mosunetuzumab by intravenous (IV) administration is FDA- and EMA-approved in relapsed/refractory (R/R) FL after ≥2 prior lines of therapy. Interim results from the Phase II MorningSun study (NCT05207670) demonstrated promising efficacy and manageable safety of mosunetuzumab SC in pts with previously untreated HTB FL (Flinn et al. ASCO 2025). We report 12-month follow-up efficacy and safety data of mosunetuzumab SC in pts with previously untreated HTB FL in the MorningSun study, including pts who received optional maintenance therapy. Methods: Pts with previously untreated HTB FL, per Groupe D'Etude des Lymphomes Folliculaires criteria, and Eastern Cooperative Oncology Group performance status of 0–2 were enrolled, primarily from United States (US) community sites. Mosunetuzumab SC was administered as step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) followed by 45mg on D1 of each 21-day cycle, for up to 17 cycles (1 year). Pts with a partial or complete metabolic response (CMR) after C17 could receive optional mosunetuzumab maintenance treatment (45mg every 8 weeks for up to 1 year). The primary endpoint was progression-free survival (PFS) rate at 1 year. Key secondary endpoints included objective response rate (ORR), duration of response (DOR), duration of complete response (DOCR) and safety. Exploratory analysis of ctDNA levels was performed using the AOA-NHL assay. Results: As of February 10, 2025, 103 pts were enrolled (n=82 pts from community sites, n=21 pts from academic sites). Overall, the median age was 65 years (range: 24–86), 51.5% of pts were female and most pts had Ann Arbor stage III/IV disease (91.3%) and a FLIPI score ≥2 (78.6%). In total, 69 pts completed initial treatment (17 cycles), 33 discontinued (primarily due to progressive disease [PD; n=18] and adverse events [AEs; n=5]), and 1 pt was continuing treatment. After 17 cycles, 68 pts were eligible for maintenance treatment, of whom 46 received maintenance, and 15 were continuing maintenance treatment at the time of data cut-off. Median duration of follow-up was 22.3 months (95% confidence interval [CI]: 20.9–24.1). The 12-month PFS rate was 85.5% (95% CI: 76.2–91.3). The ORR was 87.4% (95% CI: 79.4–93.1); 64.1% of pts had a CMR. The 12-month OS rate was 91.9% (95% CI: 84.5–95.9); the 12-month DOR and DOCR rates were 89.6% (95% CI: 80.2–94.7) and 91.1% (95% CI: 79.4–96.2), respectively. Of the 46 pts who received maintenance, no pts experienced PD, and 1 pt died (reason unknown). Of the 22 pts who were eligible but did not receive maintenance, 1 pt had PD. The most common AEs (≥30%) were injection-site reaction (67.0%), fatigue (44.7%), cytokine release syndrome ([CRS] 34.0%), headache (32.0%), and nausea (32.0%). Grade (Gr) ≥3 AEs and serious AEs were reported in 47.6% and 35.9% of pts, respectively. Five pts experienced Gr 5 AEs: COVID-19 pneumonia (n=2) and cardiogenic shock, unexplained death, pneumonia (n=1 each). Infections occurred in 77.7% of pts and were predominantly Gr 1/2 (Gr 1: 10.7%; Gr 2: 47.6%; Gr 3: 12.6%; Gr 4: 3.9%), with the most common infection being COVID-19 (24.3%). Of 3 (2.9%) Gr 5 infections reported, 1 occurred during initial treatment (COVID-19), 1 during maintenance (pneumonia), and 1 occurred 2.8 months after completion of treatment (COVID-19). AEs were reported in 80.4% of pts in the maintenance phase, mostly Gr 1/2 events. No CRS events occurred during maintenance treatment. Infections were reported in 45.7% of pts during maintenance, with the majority being Gr 1/2 events (37.0%), and were similar types of infection as during initial therapy. ctDNA levels were assessed in a subset of pts who achieved a CMR; 86.4% (19/22) of pts were minimal residual disease (MRD) negative (p-value cut-off 0.005).Conclusions: Longer follow-up of mosunetuzumab SC with optional maintenance treatment continues to demonstrate promising PFS and OS rates, and a manageable safety profile in pts with previously untreated HTB FL. Exploratory analysis of ctDNA in a subset of CMR pts showed MRD negativity in 86.4%, thus supporting fixed treatment duration of mosunetuzumab SC. Overall, these data support the outpatient administration of mosunetuzumab SC in US community practices and further evaluation of mosunetuzumab-based treatment in first-line HTB FL.

Abstract Background: Mosunetuzumab (Mosun) is an off-the-shelf, CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells, including those that cause malignant disease. Mosun is FDA- and EMA-approved for relapsed/refractory follicular lymphoma (FL) after ≥2 prior lines of therapy as a fixed-duration intravenous treatment, and can be given in an outpatient setting without mandatory hospitalization. Initial Phase I/II data with Mosun monotherapy have shown notable efficacy and manageable safety in patients with previously untreated diffuse large B-cell lymphoma (DLBCL; NCT03677154; Olszewski et al. ASH 2022). The Phase II MorningSun study is the first to assess the efficacy and safety of subcutaneous (SC) Mosun monotherapy in elderly/unfit patients with previously untreated DLBCL; we report an interim analysis for this study. Methods: MorningSun (NCT05207670) is an open-label, multicenter, Phase II, basket study evaluating the safety, efficacy, and pharmacokinetics of Mosun SC monotherapy in patients with B-cell non-Hodgkin lymphoma. In the DLBCL cohort, eligible patients aged ≥80 years or aged 65–79 and considered ineligible for chemoimmunotherapy (CIT) were enrolled, primarily in US community sites. Hospitalization was not mandatory. Step-up doses of Mosun SC were administered on Day (D) 1 (5mg), D8 (45mg) and D15 (45mg) of Cycle 1, followed by 45mg on D1 of 21-day cycles, for up to 17 cycles or until unacceptable toxicity. The primary endpoint in this cohort was progression-free survival (PFS) rate at 24 months after first study treatment. Secondary endpoints included objective response rate (ORR), complete response (CR) rate, time to response (TTR), duration of response (DOR), duration of complete response (DOCR), overall survival (OS), and safety. An exploratory circulating tumor DNA analysis was performed using an AOA-NHL assay. Results: Overall,49 patients were enrolled, the majority at community sites (community, n=34; academic, n=15). Thirty-six patients had DLBCL, 6 had high-grade [Gr] B-cell lymphoma, 2 had T-cell/histiocyte-rich large B-cell lymphoma, and 1 had Gr 3B FL (histology missing/other lymphoma, n=4). Median age was 82.5 years (range: 71–101); 63.3% and 20.4% of patients had an ECOG performance status of 1 and 2, respectively; 40.8% had Ann Arbor stage IV disease; 51.0% had extranodal involvement; 18.4% had bulky disease; and 53.1% had an IPI score of 3–5. At the clinical cut-off date of February 10, 2025, 23 (46.9%) patients had discontinued treatment, mainly due to progressive disease (n=12, 24.5%) or an adverse event (AE; n=5, 10.2%); the median duration of follow-up was 12.5 months (range: 1.4–30.8) and the median number of cycles received was 14 (range: 1–17). The PFS rate at 12 months was 68.8% (95% confidence interval [CI]: 52.1–80.6) and OS rate at 12 months was 77.2% (95% CI: 61.1–87.3). The ORR and CR rates were 73.5% and 59.2%, respectively. Median TTR was 2.7 (range: 2.5–6.1) months. DOR and DOCR rates at 12 months were 84.6% (95% CI: 66.8–93.3) and 95.0% (95% CI: 69.5–99.3), respectively. The most common AE (any grade) was injection site reaction (n=25, 51.0%), which was mostly Gr 1 (n=24, 49.0%). Gr 3/4 AEs occurred in 65.3% (n=32) of patients, most commonly infections (16.3% [n=8]) and decreased neutrophil count (10.2% [n=5]); serious AEs occurred in 42.9% (n=21) of patients. Four patients experienced Gr 5 AEs (congestive cardiac failure, volvulus, unexplained death and intracranial hemorrhage, n=1 each); none were related to Mosun per investigator assessment. Infections occurred in 46.9% (n=23) of patients (Gr 1/2, 30.6% [n=15]; Gr 3, 16.3% [n=8]); no Gr 4/5 infections were observed. No immune effector cell-associated neurotoxicity syndrome events occurred. Cytokine release syndrome was reported in 12.2% (n=6) of patients, with 10.2% (n=5) Gr 1 and 2.0% (n=1) Gr 2 events, all of which resolved. In evaluable patients with a CR (n=16), 68.8% (n=11) of patients were minimal residual disease negative (p-value cut-off 0.005).Conclusions: There remains an unmet need for effective chemotherapy-free options in previously untreated elderly and CIT-ineligible patients with DLBCL. Interim data from MorningSun demonstrate that fixed-duration Mosun SC monotherapy is active in these patients, with promising efficacy and a manageable safety profile, with predominantly mild-to-moderate AEs, allowing for outpatient administration in the community practice setting.

Abstract Background: There remains an opportunity for new therapies to improve long-term outcomes for patients with low-tumor burden follicular lymphoma (FL). Mosunetuzumab is an off-the-shelf CD20xCD3 bispecific antibody, approved as an intravenous therapy for patients with relapsed/refractory FL after ≥2 lines of systemic therapy. Mosunetuzumab can be administered in the outpatient setting as a fixed-duration regimen. In an open-label, multicenter, Phase II study conducted mainly across US community sites (MorningSun; NCT05207670), mosunetuzumab administered subcutaneously (SC) induced high response rates with a manageable safety profile in patients with previously untreated low-tumor burden FL (Burke et al. ASH 2024). Here we present updated efficacy and safety data for mosunetuzumab SC in patients with previously untreated, low-tumor burden FL. Methods: Patients had untreated Grade 1 or 2 low-tumor burden FL per Groupe d'Etude des Lymphomes Folliculaires criteria, Ann Arbor stage III/IV disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2. Mosunetuzumab SC was administered with step-up dosing in Cycle 1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg), then 45mg on D1 of each 21-day cycle. Hospitalization was not mandatory. Patients with a complete metabolic response after 8 cycles could complete therapy and patients with a partial metabolic response or stable disease continued treatment for up to 17 cycles. The primary endpoint was progression-free survival (PFS) at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), duration of response (DOR), duration of complete response (DOCR), and safety. Exploratory analyses assessed pharmacodynamic changes in B-cell subsets. Here, we report interim data. Results: As of February 10, 2025 (clinical cut-off date), 101 patients were enrolled from US community (n=56) and academic (n=45) centers; 52 patients had completed treatment, 21 had discontinued (mainly due to adverse events [AEs; n=6] and progressive disease [n=5]), and 28 were ongoing on treatment. Median age was 65 years (range: 34–82). Most patients had an ECOG PS of 0 (81.2%) or 1 (18.8%) and 43 patients (42.6%) had extranodal involvement. Median duration of follow-up was 13.8 months (95% confidence interval [CI]: 11.5–16.9) and median number of cycles received was 10 (range: 3–17). The ORR was 98.0% (95% CI: 93.0–99.8) and the complete response rate was 89.1% (95% CI: 81.3–94.4). Median TTR was 2.8 months (range: 1.4–8.3). Landmark DOR and DOCR rates at 12 months were 91.8% (95% CI: 81.5–96.5) and 95.7% (95% CI: 82.6–99.0), respectively. The 12-month PFS and OS rates were 92.0% (95% CI: 83.8‒96.1) and 99.0% (95% CI: 93.2‒99.9), respectively. The most common AE was injection-site reaction (ISR, 81.2%; Grade 1, 74.3%; Grade 2, 5.9%; Grade 3, 1.0%). Grade 3/4 AEs were reported in 51.5% of patients; the most common (≥10%) events were cytopenias (36.6%) and infections (11.9%). Cytokine release syndrome (CRS) was reported in 48.5% of patients (Grade 1, 40.6%; Grade 2, 7.9%). Overall,infections occurred in 63.4% of patients (Grade 1, 7.9%; Grade 2, 42.6%; Grade 3, 11.9%; Grade 5, 1.0%) with the most common (≥10%) being upper respiratory tract infection (21.8%), COVID-19 (17.8%), sinusitis (13.9%), and pneumonia (11.9%). At the time of data cut-off, ISR, CRS, and infection AEs were resolved at rates of 98.2%, 100%, and 89.0%, respectively. Two patients had a Grade 5 AE (sepsis, n=1; unknown cause, n=1).No immune effector cell-associated neurotoxicity syndrome events were reported. B-cell depletion was observed following the first dose of mosunetuzumab, with subsequent B-cell recovery observed within six months of treatment completion. Conclusions: Fixed-duration mosunetuzumab SC demonstrates high efficacy rates with deep and sustained responses in patients with previously untreated, low-tumor burden FL. The manageable safety profile supports ease of outpatient administration without mandatory hospitalization, including in community oncology practices. Additionally, exploratory analyses demonstrating B-cell recovery after treatment completion also substantiate the use of mosunetuzumab SC as a fixed-duration regimen. These data support further evaluation of mosunetuzumab SC in patients with previously untreated, low-tumor burden FL.

7014 Background: Mosun is a CD20xCD3 bispecific antibody that can be administered in the outpatient setting for a fixed duration. Intravenous Mosun is approved for the treatment of relapsed/refractory FL after ≥2 prior lines of therapy. Mosun SC achieved high response rates with manageable safety in patients with 3L+ FL in a pivotal Phase II study (Bartlett et al. ASH 2024). We report the efficacy and safety of Mosun SC in patients with previously untreated high-tumor burden FL in the Phase II MorningSun study (NCT05207670). Methods: Patients with previously untreated high-tumor burden FL, per GELF criteria, were enrolled into this cohort. Mosun SC was administered with step-up dosing in Cycle (C)1 (Day [D]1, 5mg; D8, 45mg; D15, 45mg) then 45mg on D1 for up to 17 cycles (1 year; 21-day cycles). Patients with a partial or complete metabolic response (CMR) after C17 could receive additional Mosun maintenance therapy (45mg every 8 weeks for up to 1 year). Corticosteroid prophylaxis to reduce the risk of cytokine release syndrome (CRS) was mandatory in C1–2 and optional thereafter. The primary endpoint was progression-free survival (PFS) rate at 24 months. Key secondary endpoints included objective response rate (ORR), time to response (TTR), and safety. Results: As of May 29, 2024, 102 patients were enrolled; 55 patients had completed initial treatment (17 cycles), 31 had discontinued (most commonly due to progressive disease [n=19] and adverse events [AEs; n=4]), and 16 were ongoing initial treatment. Forty-two patients received maintenance treatment, and this was ongoing in 38 patients. Median age was 65 years (range: 24–86); 52.0% of patients were female. Most patients had Ann Arbor stage III/IV (91.2%) and a FLIPI score ≥2 (78.4%). Median duration of follow-up was 13.9 months. The 12-month PFS rate was 82.8% (95% confidence interval [CI]: 73.0–89.3). ORR was 87.3%; 60.8% of patients had a CMR. Among the 89 patients with a response, the median TTR was 2.7 months (range: 1.2–5.8). The most common AEs (≥30%) were injection-site reaction (57.8%), fatigue (42.2%), CRS (34.3%), headache (31.4%), and nausea (30.4%). Grade ≥3 AEs and serious AEs (SAEs) were reported in 44.1% and 29.4% of patients, respectively. CRS events were all Grade 1/2 and SAE of CRS occurred in 10.8% of patients (Table); all events resolved. Conclusions: Mosun SC demonstrated promising efficacy in patients with previously untreated high-tumor burden FL. The manageable safety profile, including rate of CRS, supports the administration of fixed duration Mosun SC in an outpatient setting. Additional data, including cytokine profiling and T/B/NK dynamics, will be presented. Clinical trial information: NCT05207670 . CRS events, n (%) PatientsN=102 Any grade 35 (34.3) Grade12 30 (29.4)5 (4.9) SAE 11 (10.8) ManagementSteroidsTocilizumabSteroids + tocilizumabFluidsICU admission 8 (7.8)6 (5.9)3 (2.9)3 (2.9)2 (2.0)

Background: Mosunetuzumab (Mosun), a CD20xCD3 bispecific antibody, received accelerated approval for the intravenous treatment of patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) who have received ≥2 prior lines of systemic therapy. Mosun can be administered in the outpatient setting with a fixed treatment duration. In an ongoing Phase I/II study, Mosun administered subcutaneously (SC) induced durable responses with a manageable safety profile in pts with previously untreated low-tumor burden FL (LTB; Flinn et al. ASH 2023). Efficacy, safety and pharmacodynamic profiles of Mosun SC are being evaluated in an open-label, multicenter, Phase II study (MorningSun; NCT05207670) in pts with B-cell non-Hodgkin lymphomas, including previously untreated FL. Here we present >8-month follow-up efficacy, safety and biomarker data for Mosun SC in first-line, LTB FL. Methods: Pts had untreated Grade (Gr) 1 or 2 FL, LTB by Groupe d'Etude des Lymphomes Folliculaires criteria, Ann Arbor stage III/IV disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. Mosun SC injection was administered with step-up dosing in Cycle (C) 1 (Day [D] 1, 5mg; D8, 45mg; D15, 45mg), then 45mg on D1 of each 21-day cycle. Hospitalization was not mandatory. Pts with a complete metabolic response (CMR) after C8 could complete therapy. Pts with a partial metabolic response (PMR) or stable disease continued treatment for up to 17 cycles. Dexamethasone premedication was mandatory in C1 and C2 and optional thereafter. The primary endpoint was progression-free survival at 24 months. Exploratory analyses assessed cytokine levels in pts with versus without cytokine release syndrome (CRS) and pharmacodynamic changes in T and B cells in a subgroup of pts. Results: As of February 7, 2024, 65 pts were enrolled in US community (n=41) and academic (n=24) centers. At baseline, median age was 63 years (range: 34-82). Most pts had an ECOG PS of 0 (83.1%) or 1 (15.4%); 29 pts (44.6%) had extranodal involvement and 3 pts (4.6%) had B symptoms. Median duration of follow-up was 8.6 months (95% confidence interval [CI]: 5.7-10.9). Median number of cycles was 8 (range: 1-17). Among 60 pts with ≥1 post-baseline tumor assessment, the objective response rate was 95.0% (95% CI: 86.1-99.0; n=57) and CMR was 83.3% (95% CI: 71.5-91.7; n=50). Median time to response was 2.8 months (range: 2.3-8.3). At data cut-off, responses were ongoing in 48 pts with a CMR and in 5 pts with a PMR. In 64 safety-evaluable pts, the most common adverse event (AE) was injection-site reaction (70.3%; Gr 1, 65.6%; Gr 2, 4.7%). CRS by ASTCT occurred in 30 pts (46.9%; Gr 1, 39.1%; Gr 2, 7.8%); CRS events presented early in C1 (53.1%; Gr1, 45.3%; Gr2, 7.8%) and C2 (Gr1, 1.6%). Nineteen pts received CRS treatment (tocilizumab, 7.8%; steroids, 7.8%; tocilizumab + steroids, 4.7%; fluids, 3.1%; low-flow oxygen, 1.6%); 8 pts had a serious AE and were hospitalized. All CRS events resolved. Other common AEs included headache (45.3%; Gr 1, 29.7%; Gr 2, 15.6%), fatigue (45.3%; Gr 1, 35.9%; Gr 2, 9.4%), maculo-papular rash (31.3%; Gr 1, 14.1%; Gr 2, 15.6%; Gr 3, 1.6%), and increased alanine aminotransferase (28.1%; Gr 1, 21.9%; Gr 2, 4.7%; Gr 3, 1.6%). Gr 3/4 AEs in ≥5% of pts were neutropenia without fever (12.5%; Gr 3, 4.7%; Gr 4, 7.8%) and lymphopenia (7.8%; Gr 3, 1.6%; Gr 4, 6.3%). Suspected immune effector cell-associated neurotoxicity syndrome occurred in 2 pts (confusional state, Gr 1, n=1; Gr 2, n=1); all events resolved. Infections occurred in 30 pts (46.9%; Gr 1, 7.8%; Gr 2, 31.3%; Gr 3, 7.8%) with the most common (≥10%) being COVID-19 (17.2%; Gr 1, 7.8%; Gr 2, 7.8%; Gr 3, 1.6%) and upper respiratory tract infections (12.5%; Gr 1, 3.1%; Gr 2, 9.4%). One pt had a Gr 5 (fatal) AE 13.7 months after treatment was completed (reported as unrelated to Mosun; cause unknown). After the first Mosun dose, cytokine levels significantly increased on C1D2 (interleukin-6, n=44, p≤0.001; interferon-γ and tumor necrosis factor-α, n=41, p≤0.001). This spike in cytokine levels did not differ in pts with (n=19) versus without (n=25) CRS events in C1. Conclusions: Mosun SC monotherapy shows encouraging high efficacy as a fixed-duration treatment in first-line LTB FL. A manageable safety profile was reported, supporting ease of access for patients with drug administration in outpatient settings. Longer follow-up is needed to confirm long-term durability of response and safety.

Abstract Background:Racial disparities in multiple myeloma (MM) outcomes are well established. Clinical characteristics and cytogenetic abnormalities dictate outcomes in MM but historically they have been mostly defined in White patients with paucity of information regarding racial-ethnic minorities. Hispanics are the fastest growing racial-ethnic subgroup in United States and have the worst overall survival (OS) in MM but differences in disease presentation among Hispanics compared to Whites, the historical control, are undefined. Methods: MM patients seen at Mayo Clinic in Florida (MCF) and Arizona (MCA) between 1/1/2000-06/15/2017 were included. Patient and disease characteristics including gender, age at diagnosis, bone marrow (BM) plasmacytosis, laboratory data [M spike, creatinine (Cr), beta-2-microglobulin (B2M), Hemoglobin (Hb), calcium (Ca)], MM subtype [IgG, IgA, light chain (LC), other], LC subtype (κ, λ, biclonal), presence of lytic bone lesions, disease stage (DS, ISS, R-ISS), mSMRT cytogenetic risk category, presence of individual cytogenetic mutations (deletions, translocations, gains, trisomy/hyperdiploidy) was collected. Comparisons between Hispanic study cohort characteristics and historical control were made by Chi-square, Fischer's exact and Signed rank tests, where applicable, using data from previous publications [Kyle et al, 2003 (n=1027) and Fonseca et al, 2003 (n=351)]. Patients with missing data on a certain clinical or disease feature were not included in the statistical analysis of that specific characteristic. Results: A total of 1705 MM patients were screened and 266 Hispanic patients seen at either site between the specified dates were identified for the analysis. These included equal number of males and females (n=133 each) with a median age of 58 years (range 25-87). IgG disease was seen in 52% with IgA and LC subtypes in 23% each. LC subtype was κ in 67%, λ in 31% and biclonal in 2% cases. Lytic and extramedullary disease were noted in 71% and 44% patients, respectively. DS and R-ISS stage at the time of MM diagnosis was not available in most patients while ISS stage among 150 patients showed stage 1, 2 and 3 in 48%, 28% and 24% patients, respectively. mSMART risk categories were present in 226 patients and included high, intermediate and standard risk in 12%, 11% and 77% patients, respectively. Of these 226 patients, cytogenetic disease prior to starting any MM treatment was available in 153 patients with similar risk category distribution. Median follow up for the whole Hispanic cohort was 38.6 months with a median OS 10.7 years (Figure 1). Comparison with historical control datasets which were 97% or greater comprised of White patients showed some significant differences for the Hispanic cohort including gender distribution, median age, BM plasmacytosis at the time of diagnosis, median Hb, Cr or M spike at presentation, light chain subtype, presence of lytic bone disease and certain cytogenetic alterations including t(4;14) and del13q/monosomy (Table 1). We did not note differences in high-risk cytogenetics between Hispanics and historical White controls. Conclusions: We report the first description of clinical and cytogenetic characteristics of Hispanic MM patients. The current and historical datasets that we have used are all from Mayo Clinic experience, thus making reasonable comparisons possible. We were able to confirm previous reports of demographic differences in Hispanics e.g., younger age at diagnosis. While some characteristics were significantly different, the clinical and cytogenetic differences we note do not clearly explain the inferior OS noted for Hispanics in population-based studies. Significant differences that we report warrant continued exploration in larger institutional and public databases in addition to a continued look into healthcare access and utilization. An ongoing collaborative analysis with data from Mayo Clinic, University of Miami and University of Southern California, Los Angeles is ongoing. Disclosures Fonseca: AMGEN: Consultancy; Jansen: Consultancy; Mayo Clinic & Dr Fonseca: Patents & Royalties: Prognostication of myeloma via FISH, ~$2000/year; Celgene Corporation: Consultancy, Research Funding; Merck: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pharmacyclics: Consultancy; Novartis: Consultancy. Kelly: Pharmacyclics: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Jannsen: Honoraria. Sher: LAM Therapeutics, Inc: Research Funding. Ailawadhi: Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Abstract Background: SCT is a standard therapeutic approach for patients with MM and has contributed to improved outcomes. While SCT utilization in MM has increased for all racial-ethnic subgroups over time, population-based studies have repeatedly shown that racial minorities are less likely to receive it. We explored factors that determine SCT utilization among patients within a given race to understand intra-racial disparities and how to address them in order to maximize the use of this imperative treatment among eligible patients. Methods: The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004-2013 was studied. Cases without information on the selected patient or facility characteristics evaluated in this analysis, including SCT use, race, median income, insurance status or facility type of initial MM diagnosis and/or treatment were excluded. The association between utilization of SCT as part of initial therapy of MM and socio-demographic factors was studied stratifying patients into mutually exclusive racial-ethnic subgroups non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA) and others using multivariate GEE logistic regression analysis (clustered on facility ID). Interactions between race and patient/facility characteristics and SCT utilization were tested using similar methods but including all races. Results: Of the 123480 unique MM patients in NCDB diagnosed between 2004-2013, 111799 met the inclusion criteria. Of these, 15021 patients (13.4%) received SCT as part of initial MM therapy. Of those who received SCT, 77.5% were NHW (14.4% of all NHW), 15.1% NHB (10.3% of all NHB), 5.2% Hispanics (13.2% of all Hispanics), 2% NHA (15.5% of all NHA) and <1% others. There was no difference by gender but significantly reduced odds of receiving SCT were noted for every 10-year increase in age at diagnosis for all racial subgroups. NHA were the only subgroup not to have a significant year-wise increase over time in odds of receiving SCT between 2004-2013. A significant increase in SCT utilization was seen with increasing median income (quartiles; 2008-2012 data), for NHW and Hispanics but not for NHB and NHA, while increased education (% population with high-school degree; 2008-2012 data) was associated with a significant increase in SCT use for NHW and NHB, but not among Hispanics or NHA. An increase in great circle distance (GCD) from the treating facility as well as a lower Charlson-Deyo comorbidity index (CCI) was associated with significantly increased odds of receiving SCT for all racial groups. Insurancepayer status significantly affected odds of receiving SCT among all races with those having private insurance to be most likely to receive SCT among NHW, NHB and Hispanics while those with "other government" insurance payer type being most likely among NHA. Among treating facility characteristics, patients of all races were more likely to receive SCT if treated at an academic/researchfacility (including NCI-designated centers) or centers with highest quartile of patientvolume seen. For analysis by geographicalregion, NHW and NHA had the highest odds of receiving SCT in mountain region but there was no impact of geography on SCT for NHB or Hispanics. Odds ratio (OR) of receiving SCT as part of initial MM therapy by socio-demographic and facility characteristics for patients of individual racial subgroups are shown in Table 1. A significant interaction between odds of receiving SCT and various racial subgroups was noted for patient age at diagnosis (p<.001, decreased odds among NHW and NHA), GCD from treating facility (p=0.013, increased odds among NHB and NHA), CCI (p=0.043, decreased odds among NHA) and treatment facility volumes (p=0.046, increased odds among NHA and Hispanics). Conclusions: In the largest analysis exploring socio-demographic factors affecting SCT utilization in MM we note a significant disparity within races for who gets SCT as a part of initial MM management and who does not. While some of these factors are non-modifiable, others including access to healthcare, income, insurance and literacy levels, proximity to treatment center, treating facility type as well as volumes are modifiable and appear to be barriers to SCT among in some races, while not in others. These must be addressed to minimize disparities within racial subgroups, especially the minorities and realize maximal benefit of SCT for MM. Disclosures Ailawadhi: Novartis: Consultancy, Honoraria; Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Sher: LAM Therapeutics, Inc: Research Funding.

Background: Survival of patients with MM has improved significantly over recent years due to therapeutic advancements. Population-level data has shown that a substantial proportion of MM patients may die early after their diagnosis and real-world evidence regarding early mortality (≤6 months after MM diagnosis) has been conflicting. We evaluated the trends, causes and predictors of early mortality among newly diagnosed MM (NDMM) patients in the real world. Methods: We used Surveillance Epidemiology and End Results (SEER) database, to identify all adult patients (age ≥ 18 years) who were diagnosed of MM from 1975 to 2015. Data on age, gender, geographical regions, year of diagnosis, survival time, vital status at 6 months after diagnosis and cause of death (COD) were extracted. Ages were categorized as quartiles while period of diagnosis for multivariate analysis were categorized by running a joinpoint analysis separately for the all-cause and myeloma-specific mortality. To look at trends in early mortality, we estimated proportion of deaths for each year and plotted it as a scatterplot against the year of diagnosis and fitted it in the join point regression model by applying the NCI's Join point Regression Program, Version 4.5.0.1. By this method we identified the year(s) when a trend change was produced, calculated the annual percentage change (APC) in rates between trend-change points, and the average annual percentage change (AAPC) in the whole period studied. To correct for known errors with COD attribution, we applied a special COD variable which has been recently developed by the SEER program to indicate if the death was due to the primary cancer diagnosis or other causes. A multivariate analysis was conducted to analyze the predictors of all-cause and myeloma-specific mortality within 6 months by fitting into logistic regression model. Results: Of 90,975 NDMM patients, early mortality due to any cause was noted in 18,810 (20.7%). For the whole cohort, median age was 68 years, majority of the patients were males (53.1%), of non-Hispanic white (NHW) race/ethnicity (65.5%) and were diagnosed in SEER registries in the western region (53.9%). An overall survival (OS) of ≤6 months was seen for approximately 22% of NHW but 18% of non-Hispanic blacks (NHB) and Hispanics. OS of ≤6 months was seen in 10% of patients in the first quartile of age (<60 years) as compared to 36% of patients in the 4th quartile (≥78 years). By geographical regions, 23.3% of MM patients in the Midwest had ≤6-month OS as compared to only 18.4% in the Northeast. The most common early mortality COD was MM in 74.7% of the patients, followed by cardiovascular (11.9%), other (8.8%) and infectious causes (3.1%). The overall pattern of COD at 6 months was similar to COD at any time in the whole cohort. Joinpoint regression analysis of trends data resulted in 1 joinpoint for all-cause 6-month mortality while 2 joinpoints were noticed for myeloma-specific mortality (Figure 1). A steep decline in mortality was noticed in the more recent time periods for both, all-cause (2006-2015) and myeloma-specific (2003-2015) mortality rates with an AAPC of 3.93 (95%CI p<0.001) for all-cause and 3.95 (95%CI p<0.001) for myeloma-specific mortality. Prior to 2006, the decrease in all-cause mortality was only modest whereas decrease in myeloma-specific mortality witnessed a sharp decline from 1975-1987 as well. On MVA, advanced age (p<0.001), NHW race/ethnicity and Midwest geographic region (p<0.001) were associated with higher likelihood of mortality while female gender (p<0.001), more recent period of diagnosis (p<0.001), and "other" races (not NHW, NHB or Hispanics) (p<0.001) were associated with lower risk of mortality. Conclusion: Our results show that early mortality due to MM remains high despite therapeutic improvements and there are significant gender, racial and geographic disparities for this phenomenon. However, significant declines in all-cause and MM-specific early mortality in the more recent times are promising. The risk of early mortality is higher among men, older patients, NHW and Midwest region. A focus on interventions to reduce early mortality, including early diagnosis, use of efficacious anti-MM therapy and aggressive supportive care should be directed at groups with high-risk for early mortality from MM. Disclosures Chanan-Khan: Millennium: Research Funding; Ascentage: Research Funding; AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment. Ailawadhi:Celgene: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Cellectar: Research Funding; Janssen: Consultancy, Research Funding.

Multiple myeloma (MM) treatment has advanced significantly over the last 2 decades. In most patients, the disease course has been altered from early fatality to chronic morbidity with multiple lines of treatment. The MM treatment paradigm has shifted toward treating patients before end-organ damage occurs. Thus, timeliness of treatment initiation in this era might improve patient outcomes. This is the first report to our knowledge analyzing disparities and trends in treatment timeliness of patients with MM using the National Cancer Database. Multiple factors affected the timing of treatment initiation in MM and disparities were found. We noted that initiation of treatment was delayed in women (odds ratio [OR], 1.15; 95% CI, 1.1 to 1.2) and blacks (OR, 1.21; 95% CI, 1.14 to 1.28; reference, whites) and in patients diagnosed in more recent years (2012-2015; OR, 1.15; 95% CI, 1.1 to 1.22; reference, 2004-2007). Patients were likely to start treatment earlier if they were age ≥ 80 years (OR, 0.83; 95% CI, 0.76 to 0.9; reference, age < 60 years), were uninsured (OR, 0.81; 95% CI, 0.72 to 0.91; reference, private insurance), had Medicaid (OR, 0.87; 95% CI, 0.79 to 0.95; reference, private insurance), were treated in a comprehensive community cancer program (OR, 0.7; 95% CI, 0.65 to 0.77; reference, community cancer program), lived in a location other than the US Northeast, or had a higher Charlson comorbidity score. Patient education and income levels did not affect time to treatment initiation. Particular aspects of these disparities could be explained by our current health care system and insurance rules, whereas others need to be investigated more deeply.

Background: Ibrutinib (ibr) is a small-molecular inhibitor of Bruton's Tyrosine Kinase (BTK), active in the treatment of various B-cell malignancies. B-cell receptor signaling blockade by BTK inhibition using ibr down regulates IRF4 (survival transcription factor) which is down regulated by lenalidomide (R) as well, suggesting possible synergistic effect on cell death. Higher doses of ibr (560-840 mg daily) have been used in combination regimens for MM with no significant dose-limiting toxicities (DLTs) but the combination of ibr and len has not been previously tested. We present safety and preliminary efficacy of the combination ibr, R, and dexamethasone (d) in RRMM patients. Methods: This is a phase I dose escalation study (NCT03015792) of 28-day cycles of ibr (420 mg daily, 560 mg daily, 700 mg daily or 840 mg daily) days 1-28 in combination with R 25 mg PO days 1-21, and d 40 mg PO weekly utilizing a 3+3 dose-escalation design. Eligible RRMM patients had progression after ≥2 prior lines of treatment, measurable disease as per International Myeloma Working Group criteria, ECOG performance status ≤2, adequate bone marrow (BM) (absolute neutrophil count ≥1.0 x 109, platelets ≥50,000 cells/mm3 for patients with BM plasmacytosis <50% or ≥30,000 cells/mm3 for patients with BM plasmacytosis ≥50%), kidney (creatinine clearance ≥30 mL/min), and liver function [total bilirubin ≤1.5 x upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase ≤3 x ULN], and PT/INR ≤1.5 X ULN. Treatment was to be continued till progressive disease (PD) or any unacceptable toxicity. The primary objective was to determine the maximum tolerated dose (MTD) of ibr+Rd in RRMM and secondary objective was to evaluate safety profile of this regimen. Results: As of July 26 2019, 18 patients had been enrolled in the trial. Three patients had to be replaced (2 at 700 mg cohort, 1 each due to withdrawal and ineligibility, and 1 at 840 mg due to withdrawal). Median age of all patients was 67 years (range 49-79) with 9 of the 15 evaluable patients being females. Evaluable patients as per ibr dose level included 3 at 420 mg, 3 at 560 mg, 3 at 700 mg, and 6 at 840 mg. Four out of 15 patients had high-risk cytogenetics. Median prior lines of treatment were 4 (range 2-13) and prior treatments included bortezomib in 87% (n=13), carfilzomib in 47% (n=7), ixazomib in 47% (n=7), lenalidomide in 87% (n=13), pomalidomide in 40% (n=6), thalidomide in 40% (n=6), daratumumab in 60% (n=9), and stem cell transplant in 53% (n=8). High risk cytogenetics [del 17p, t(4;14), t(14;16), t(14;20)] were noted in 4 of the 15 evaluable patients (27%). Median follow up for alive patients was 8.6 months (range 1.1-25.1 months) and the median number of treatment cycles was 2 (range 1-5). Most common reason for treatment discontinuation was PD (40%) followed by adverse events (AEs) (26.7%). Only 1 DLT possibly related to ibr was a grade 3 rash at the 840 mg dose. Grade 3/4 AEs at least possibly related to study treatment included anemia (n=3), thrombocytopenia (n=3), neutropenia (n=3), leucopenia (n=3), lymphopenia (n=2), febrile neutropenia (n=1), and rash (n=2). Overall, the most common all grade AEs included anemia (n=12), thrombocytopenia (n=10), fatigue (n=10), neutropenia (n=8), leucopenia (n=5), and diarrhea (n=5). (Figure 1) No treatment-related deaths were noted. Overall response rate (ORR) was 7% with partial response (PR) noted in 1 patient. Additionally, 1 patient achieved a minor response (MR) and 10 patients had stable disease (SD) for a clinical benefit rate (CBR) of 80%. (Figure 2) PD was noted in 1 patient and 2 patients did not get response assessment. Ibr 840 mg (daily) with R 25 mg (days 1-21) and d 40 mg weekly was considered the MTD of this regimen. The median progression-free survival (PFS) for the 15 evaluable patients was 4.5 months (95% CI: 1.8-not reached). Conclusions: We report the first phase 1 trial of combining a BTK inhibitor with Rd in RRMM patients. MTD of ibr was determined as 840 mg (daily) in combination with R 25 mg (days 1-21) and d 40 mg weekly. This dose of ibr is consistent with some other trials showing the benefit of a higher dose of ibr in various regimens for treatment of B-cell malignancies. We noted this regimen to be well-tolerated without much high-grade AEs. Disease stabilization was noted in majority of patients. These data lay the basis for a larger trial in a more uniform cohort of patients to better define the efficacy of this regimen. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy. Chanan-Khan:AbbVie: Research Funding; Xencor: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding. OffLabel Disclosure: Ibrutinib is not FDA-approved for the treatment of multiple myeloma. The regimen of ibrutinib with lenalidomide and dexamethasone is not FDA-approved for the treatment of multiple myeloma.