Warsame, Rahma

Abstract Introduction: There is evidence that lack of a social network is a link to inferior outcomes in cancer patients. Mayo clinic performs all its stem cell transplants for multiple myeloma patients as an outpatient. This requires a full-time chaperone or caregiver for the duration of the transplant. Patients who do not have a caregiver are hospitalized for the duration of the transplant. In this study we compared outcomes between patients hospitalized for the entire transplant and those who have a caregiver and are initially managed as an outpatient.Materials and methods: All patients with multiple myeloma transplanted at the Mayo Clinic in Rochester Minnesota between 1/1/2000 and 12/31/2019 were included for analysis. Patient had to have been transplanted within 12 months of the original diagnosis. The definition of inpatient transplantation was hospitalization prior to day 0 of transplantation for conditioning and continued hospitalization until evidence of neutrophil engraftment occurred.Results: There were 41 patients who were considered inpatient transplants and 2103 that were outpatient transplants. The patients were well balanced for age, sex, serum creatinine, and international stage at diagnosis. For inpatient transplants the median days in the hospital was 21 (interquartile range 18 to 28). For outpatient transplants the median number of days in the hospital was 0 (interquartile range 0 to 6). Relapse free survival was not significantly different between the 2 groups, but overall survival was 95 versus 58 months favoring those that had transplantation as an outpatient (p=.0008). Conclusion: There appears to be in association between myeloma patients that lack a caregiver and require inpatient stem cell transplantation and overall survival.

Abstract Multiple myeloma (MM) is a plasma cell malignancy that is characterized by diverse clinical presentations. Although biochemical assessment of disease activity is commonly used to monitor treatment response, findings on magnetic resonance imaging and positron emission tomography (PET)/computed tomography (CT), among other imaging modalities, have proven to harbor prognostic value. We sought to corroborate these findings by examining the prognostic significance of fluorodeoxyglucose PET/CT scanning in the setting of newly diagnosed MM. We retrospectively analyzed 195 patients with a PET/CT available at diagnosis and at 6 months posttreatment to examine their value as an adjuvant metric to conventional hematologic responses in terms of time to next treatment (TTNT) and overall survival (OS). The median TTNT and OS for the entire cohort were 24.6 months (95% confidence interval [CI], 20.4-29.1) and 79 months (95% CI, 63.1-119.1), respectively. When comparing PET/CT negative (−) with PET/CT positive (+) patients, we found significantly prolonged median TTNT (55.2 vs 17.8 months, P < .0001) and OS (unreached vs 60.8 months, P < .0001) in the former group. We then examined the additive value of PET/CT on the hematologic response achieved at 6 months and found that PET/CT (−) is associated with significantly increased median TTNT and OS for the very good partial response (VGPR) group and the less than VGPR group. Importantly, PET/CT retained prognostic significance after adjusting for multiple other predictive variables. We conclude that a PET/CT (−) at 6 months confers a significant prognostic advantage for patients with newly diagnosed MM and adds significant value to the hematologic response assessment.

Clinical success with intravenous (IV) oncolytic virotherapy (OV) has to date been anecdotal. Here, we conducted a phase 1 clinical trial of systemic OV therapy and investigated the mechanisms of action in responding T-cell lymphoma (TCL) patients. A single IV dose of VSV-IFNβ-NIS was administered to patients with relapsed refractory hematologic malignancies to determine safety and efficacy across 4 dose levels (DL). Correlative studies were undertaken to evaluate viremia, virus shedding, virus replication and immune responses. Fifteen patients received VSV-IFNβ-NIS (7 multiple myeloma, 7 TCL, 1 acute myeloid leukemia); 3 patients were treated at each DL1 through DL3 (0.05, 0.17, and 0.5 x 1011 TCID50), and 6 at DL4 (1.7 x 1011 TCID50). There were no dose limiting toxicities. 3 of 7 patients with TCL had RECIST responses: a 3-month PR at DL2, a 6-month PR and a durable CR ongoing at 20 months at DL4. Viremia peaked at the end of infusion and no infectious virus shedding was detected. Plasma interferon-β levels, a biomarker of VSV-IFNβ-NIS replication, peaked between 4h and 48h post infusion. The patient with CR had robust viral replication with increased ell free DNA in her plasma, a very high peak IFNβ level of 18,213 pg/ml, a strong anti-VSV neutralizing antibody response, and increased numbers of tumor reactive T-cells. VSV-IFNβ-NIS as a single agent was effective in patients with TCL resulting in durable disease remissions in heavily pretreated patients. Correlative analyses suggest that responses may be due to a combination of direct oncolytic tumor destruction and immune-mediated tumor control. Further clinical testing is warranted. (This trial is registered at www.clinicaltrials.gov as NCT03017820).

AbstractCastleman disease (CD) is a rare lymphoproliferative disease characterized by diverse clinical and pathologic features. Due to its rarity, there are limited studies comparing currently available therapies. The role of autologous stem cell transplantation (ASCT) in CD has not yet been established. In this paper, we describe the clinical characteristics, treatment choices, and outcomes in 34 Mayo Clinic patients diagnosed with multicentric CD from July 1, 2003 to April 30, 2018. Eighteen patients (53%) also met the criteria for POEMS, including 14 with the osteosclerotic variant. The first‐line treatments included: steroid monotherapy (4), cytotoxic chemotherapy (6), rituximab alone (8) or with chemotherapy (2), anti‐IL6 treatment (3), and ASCT (10). The median follow‐up was 4.8 (range: 0.1–15.2) years. The 5‐ and 10‐year overall survival rates were 84% and 71%, respectively. Sixteen patients received high‐dose chemotherapy followed by ASCT during their disease course. Among those, 14 had multicentric CD associated with POEMS. There were no transplant‐related deaths. All patients had at least a partial response to ASCT, most of whom achieved a complete response. The favorable outcomes seen with ASCT in this cohort suggest that transplantation may have a role in multicentric CD, particularly for patients with multicentric CD associated with POEMS.

AbstractAchievement of a complete response (CR) in multiple myeloma (MM) correlates with improvement in survival outcomes; however, its impact on prognostic variables at baseline outside of clinical trial settings is not well described. We sought to determine the impact of achieving a CR within 2 years from diagnosis, its effect on the prognostic value of fluorescence in situ hybridization (FISH) and International Staging System (ISS) risk, and examined additional predictors of outcome among those achieving a CR in a routine clinical setting. We evaluated 1869 newly diagnosed MM patients who had ≥ 2 monoclonal protein immunofixation studies in the serum and urine available within 24 months from diagnosis, categorizing those with ≥ 2 negative serum and urine immunofixations as achieving CR. With a landmark at 24 months, median progression‐free survival (PFS) for CR versus non‐CR patients was 29.8 versus 20.9 months (p ≤ .0002); median overall survival (OS) was 104 versus 70 months (p < .0001). The impact of achieving a CR was retained after adjusting for FISH, ISS, sex, transplant status, and involved heavy chain. Baseline FISH and ISS stage were not associated with PFS or OS among patients achieving a CR. The following variables were found as predictors of inferior OS within the CR cohort: age > 75 years, male gender, hypoalbuminemia, and non‐immunoglobulin G involved heavy chain. Our study confirms that achievement of CR within 2 years from diagnosis is associated with improvement in survival outcomes and neutralization of the impact of FISH and ISS risk, thereby confirming observations from the clinical trial setting among a clinical practice cohort.

Abstract The adage for smoldering myeloma (SMM) has been to observe without treatment, until criteria for active multiple myeloma were satisfied. Definitions and risk stratification models have become more sophisticated, with prognostication tailored to include high-risk cytogenetics as per the most recent International Myeloma Working Group 2020 risk model. Moreover, progress in defining genomic evolution and changes in the bone marrow microenvironment through the monoclonal continuum have given insight into the complexities underlying the different patterns of progression observed in SMM. Given recent data showing improved progression-free survival with early intervention in high-risk SMM, the current dilemma is focused on how these patients should be treated. This case-based article maps the significant advancements made in the diagnosis and risk stratification of SMM. Data from landmark clinical trials will also be discussed, and ongoing trials are summarized. Ultimately, we outline our approach to SMM and hope to impart to the reader a sound concept of the current clinical management of SMM.

AbstractThromboses are prevalent in POEMS syndrome, but few risk factors for POEMS‐associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS‐associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Stroke accounted for 26% of all thromboses and 53% of arterial events. There were differences in baseline features between the thrombosis group and the no thrombosis group, and these were driven by patients with arterial thrombosis. Risk factors for arterial thrombosis included thrombocytosis, elevated hemoglobin/hematocrit, extravascular volume overload, and splenomegaly. Hyperprolactinemia appeared to be a risk factor for venous thrombosis. The risk of thrombosis was most striking among men with elevated hemoglobin (32% vs. 5%, p < .001) and hematocrit (42% vs. 5%, p < .001) compared to men without. Most thromboses occurred prior to POEMS directed therapy, and most that occurred during therapy happened within 3 months of diagnosis. Twenty‐one percent of patients with thrombosis had recurrence. In recognition of high overall rates of thrombosis in this population, all patients with POEMS syndrome should receive prophylactic antiplatelet therapy, and clinicians should consider anticoagulation in patients with risk factors for POEMS‐associated thrombosis.

Abstract Background: There has been a steady improvement in the survival of patients with multiple myeloma (MM) due to better understanding of the pathophysiology, use of novel agents, and risk-adapted therapy. These improvements were largely observed in clinical trials and tertiary center populations and questions remain about the generalizability of these findings to patients in community settings. Here, we compared the experience of patients seen at Mayo Clinic, Rochester (MAYO) and those followed in the Surveillance, Epidemiology, and End Results Program (SEER), to gain a better understanding of current trends in survival. Methods: We studied all patients with MM diagnosed between 01/2004 and 12/2018 seen at MAYO and those followed in SEER (18 registry research data 2000-2018, 11/2020 submission). For comparison with SEER, MAYO patients who were alive at the end of SEER follow-up (12/31/2018) were censored. For the estimation of relative survival, patients alive at the end of 2019 were censored to align with the published United States general population rate tables. Overall survival (OS) estimates were calculated using the method described by Kaplan and Meier. Multivariable-adjusted proportional hazards regression models were used to assess the association between the 5-year interval of diagnosis and overall survival. Expected OS estimates were calculated based on United States general population rate tables from the Human Mortality Database using a conditional approach. Standardized mortality ratios (SMR) were calculated by dividing the number of observed deaths by the number of expected deaths in age- and sex-matched general United States population controls. Linear regression models were fit to test for trends in SMRs over time. Results: The median age at diagnosis was 3 years lower in patients seen at MAYO compared to patients followed in SEER. The proportion of patients 75 years and older at the time of diagnosis was higher in SEER (26.3%) compared to MAYO (15.3%). Median OS was 6.7 years (95% CI 6.3-7.1) for MAYO compared to 4.6 years (95% CI 4.5-4.7) in SEER (Figure 1). When stratifying OS by year of diagnosis (in 5-year-intervals: 2004-2008, 2009-2013, 2014-2018), improvements were seen in both patient populations over time, albeit to a greater extent in patients seen at MAYO (Figures 2 and 3). The results were consistent after adjusting for age and sex in both MAYO and SEER. There were improvements in OS across all three 5-year intervals and age groups in both patient populations. In MAYO, these improvements were most pronounced during the second 5-year interval for younger patients (&lt; 65 years) and more pronounced during the last 5-year interval for older patients (&gt; 65 years). In SEER, the improvements were more gradual across the three 5-year intervals, but it was noted that the relative improvements in younger patients were greater than in older patients during the last 5-year interval. Early mortality decreased over time in both patient populations: from 11% to 6% at MAYO and from 23% to 16% in SEER (Figure 4). To examine the observed improvements in the context of the survival trends of the general population, we stratified the SMRs by patient population, age at diagnosis, and year of diagnosis, and a lack of improvement in excess mortality was observed among older patients (&gt;75 years) in both populations over time (Figure 5). Three- and five-year overall survival estimates were higher in patients seen at MAYO compared to patients followed in SEER, but the survival advantage diminished with increasing follow-up time (Figure 6). On further sub-group analysis within MAYO patients, excess mortality was observed for all International staging system (ISS) stages and patients with high-risk (HR) cytogenetics. Stratifying the SMRs by age and risk group, decreases in excess mortality were most pronounced among older patients, particularly those with indolent disease (Figure 7). Conclusions: Survival outcomes in MM continued to improve in both patient populations. These improvements were more pronounced in MAYO compared to SEER, which may be partially explained by differences in access to specialized care. The most pronounced improvements were observed among younger patients and those with favorable disease characteristics. Future efforts need to focus on improving therapies for patients with unfavorable disease characteristics and on increasing access to specialized care in community settings. Figure 1 Figure 1. Disclosures Kapoor: Glaxo SmithKline: Research Funding; Takeda: Research Funding; Sanofi: Research Funding; Amgen: Research Funding; Sanofi: Consultancy; Pharmacyclics: Consultancy; Ichnos Sciences: Research Funding; BeiGene: Consultancy; Regeneron Pharmaceuticals: Research Funding; AbbVie: Research Funding; Karyopharm: Research Funding; Karyopharm: Consultancy; Cellectar: Consultancy. Dingli: Alexion: Consultancy; Apellis: Consultancy; Janssen: Consultancy; Novartis: Research Funding; GSK: Consultancy; Sanofi: Consultancy. Gertz: Ionis Pharmaceuticals: Other: Advisory Board; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring; Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy. Lin: Novartis: Consultancy; Celgene: Consultancy, Research Funding; Juno: Consultancy; Takeda: Research Funding; Gamida Cell: Consultancy; Vineti: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Legend: Consultancy; Sorrento: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Dispenzieri: Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Research Funding; Oncopeptides: Consultancy; Alnylam: Research Funding; Pfizer: Research Funding. Kumar: Tenebio: Research Funding; Amgen: Consultancy, Research Funding; Oncopeptides: Consultancy; Bluebird Bio: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Beigene: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

Abstract Introduction: Multiple gene expression profile assays have successfully prognosticated the overall survival (OS) outcomes of patients with Newly Diagnosed Multiple Myeloma (NDMM) and are now available for use in clinical practice. The genes included in these profiles encompass several aspects of cancer biology broadly such as cell-cycle biology, energy metabolism, migration, adhesion, immune evasion etc. Since altered energy metabolism is one of the hallmarks of all cancer cells, our goal was to take a deep-dive into specific genes associated with intracellular central carbon energy metabolism (CCEM) pathways such as oxidative phosphorylation (OxPhos) as well as glycolysis and lactate fermentation (Glyco-Lac) in MM cells to determine their impact on the pathogenesis and prognosis of MM patients. Methods: Gene expression level data via RNA sequencing from the COMMPASS dataset (made available by the Multiple Myeloma Research Foundation (MMRF)) was utilized. The expression levels of all genes associated with the OxPhos (N = 118) and Glyco-Lac (N = 34) pathways were evaluated in CD138+ cells derived from patients with NDMM. Each gene was dichotomized into low and high expression groups -based on their expression level above and below the median fragments per kilobase of transcript per million (FPKM), respectively. The prognostic significance of dichotomizing each of the 152 genes in this NDMM cohort was evaluated by levels of their hazard ratios (HRs) for OS determined by the log-rank method. Genes from the OxPhos and Glyco-Lac pathways were selected based on their significant negative impact on OS, wide representation of their biologic activity throughout the pathway and high independence from each other. This resulted in the selection of 12 distinct genes of interest. A scoring system consisting of assigning a point for every gene where their FPKM was above the median yielded a minimum of 0 and a maximum of 12 for the set of genes in the OxPhos and Glyco-Lac pathways to create an energy metabolism score (EMS). Patients were then categorized into "low" (0-8) or "high" (9-12) EMS groups. In addition, patients were designated as having high-risk cytogenetics if they had any of the following: t(4;14), t(14;16), t(14;20), del17p, and Amp 1q. Survival analysis was performed using the Kaplan-Meier survival analysis and compared via the log-rank method. Finally, the distribution of the EMS score among patients within a spectrum of plasma cell disorders such as, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma and MM as well as normal plasma cells was assessed using a previously published transcriptome dataset (GSE6477). Results: A total of 766 patients were included in this study. The selected genes included in this scoring system and their biological relevance in the OxPhos and Glyco-Lac pathways are depicted in Figure A. The distribution of low and high EMS groups across ISS stage and cytogenetic risk are depicted in Figure B and C respectively. The median OS (mOS) and PFS for the high (N = 248) vs. low (N = 518) EMS groups was 55 vs. 94 months (HR: 2.41; (95%CI: 1.85-3.14); P &lt;0.0001) (Figure D) and 24 vs. 42 months (HR: 1.74; (95%CI: 1.42-2.13); P &lt;0.0001). Patients with ISS 2 stage disease categorized as having a high or low EMS score had a similar mOS to patients with ISS 3 and ISS 1 stage disease respectively (Figure E). Similarly, the mOS was similar among patients with standard risk and high-risk cytogenetics when categorized by low and high EMS (Figure F). Finally, the relative expression of most of the 12 select CCEM genes (Figure G) and the probability of a high EMS score increased among patients along the spectrum of plasma cell disorders (Normal plasma cell -&gt; MGUS -&gt; SMM -&gt; MM) (Figure H). Conclusions: The expression levels of specific genes associated with the activity of intracellular CCEM pathways such as glycolysis, lactate fermentation and oxidative phosphorylation in plasma cells provides evidence for the impact of cellular energy metabolism on the pathogenesis and survival outcomes of MM. This provides an opportunity for developing future studies aimed at understanding the energy metabolism pathways of plasma cell malignancies in greater detail so as to exploit them for diagnostic and therapeutic purposes in MM. Figure 1 Figure 1. Disclosures Kumar: Novartis: Research Funding; Amgen: Consultancy, Research Funding; Beigene: Consultancy; Carsgen: Research Funding; Merck: Research Funding; Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Roche-Genentech: Consultancy, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Dispenzieri: Alnylam: Research Funding; Sorrento Therapeutics: Consultancy; Oncopeptides: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Janssen: Consultancy, Research Funding. Kapoor: AbbVie: Research Funding; Takeda: Research Funding; Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding. Dingli: Apellis: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; GSK: Consultancy; Novartis: Research Funding; Alexion: Consultancy. Lin: Gamida Cell: Consultancy; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy; Novartis: Consultancy; Legend: Consultancy; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Sorrento: Consultancy; Merck: Research Funding; Vineti: Consultancy. Gertz: Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring; Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy. Fonseca: Aduro: Consultancy; Kite: Consultancy; Juno: Consultancy; Merck: Consultancy; Takeda: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; AbbVie: Consultancy; Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Mayo Clinic in Arizona: Current Employment; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; GSK: Consultancy.

Abstract INTRODUCTION: Belantamab mafodotin (BLMF) is a first-in-class, antibody-drug conjugate targeting B-cell maturation antigen on myeloma cells. BLMF was approved for use in patients (pts) with advanced multiple myeloma (MM). Due to the risk of ocular toxicity, it is made available through a restricted program under a Risk Evaluation and Mitigation Strategy. It is speculated that monomethyl auristatin F (MMAF), the cytotoxic payload of BLMF may be internalised by the corneal epithelium via an off-target mechanism, leading to epithelial changes. In the pivotal DREAMM-2 trial, only 1% of pts permanently discontinued treatment due to keratopathy. Data regarding BLMF-induced ocular toxicity following its commercial availability since August 2020, are sparse, and in this context, we evaluated our clinical experience with BLMF to determine the impact of its ocular toxicity on outcomes when utilized outside of stringent clinical trial settings. METHODS: We reviewed records of pts with advanced MM who were evaluated at Mayo Clinic between 09/01/2020-07/01/2021 and initiated on BLMF monotherapy following a baseline ophthalmic examination that was also performed prior to each dose, and as needed for worsening ocular symptoms. Data pertaining to ocular symptoms, best corrected visual acuity (BCVA) and corneal examinations were collected and analyzed with respect to patient outcomes. Adverse events were graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events v5.0. RESULTS: Thirty-four pts, with median age of 67 (range:49-90) years who received BLMF at the approved 2.5 mg/kg dose as their first infusion and completed at least one cycle were included. All patients were instructed to use preservative-free lubricant eye drops at least 4 times a day, starting with the initial infusion and continuing until the end of therapy, and avoid contact lenses. The median number of prior lines of therapy was 8 (range: 2-15). The median time to BLMF initiation from the diagnosis of MM was 7.5 (range: 1.3-19.7) years. The median follow-up from initiation of BLMF was 7 [95% confidence interval (CI): 5.7-8.6] months, and the median number of BLMF doses administered was 2 (range: 1-6). Twenty-seven (79%) pts experienced ocular toxicity, comprising keratopathy [n=25 (74%)] and/or decreased visual acuity [n=21 (62%)]. Table 1 outlines the keratopathy-related details. Thirteen pts (38%) developed symptomatic xerophthalmia. A clinically significant decrease in BCVA of equal or worse than 20/40 in the better-seeing eye was observed in 12 (35%) pts at a median of 1.7 (95%CI: 1.4-2.2) months of commencing BLMF. In 7 (58%) pts, it improved to better than 20/40 within a median of 3 (range: 0.7-4) months from the time of documentation of impaired BCVA following withholding treatment (n=5), with or without subsequent dose reduction or its permanent discontinuation (n=2). Treatment was permanently discontinued in 5 (15%) pts after a median of 3 doses due to grade ≥2 keratopathy. It was withheld in 9 (26%) due to grade ≥2 keratopathy. Four (12%) pts required dose reduction due to keratopathy (Table 1). Of 14 pts in whom BLMF was held or permanently discontinued due to keratopathy, 10 (77%) had disease progression within a median of 1 month (range 0.4-2.5) following BLMF interruption. Among 11 pts (32%) responded to BLMF, 45% developed grade 2 or higher keratopathy after the first dose compared to 13% of pts who were refractory to BLMF (n=23). The median duration of response was 4 (95%CI: 0.7-NR) months. Among responders, 2 pts (18%) had to permanently discontinue BLMF due to keratopathy, with subsequent progression from partial remission at 1.4 and 4.6 months following its discontinuation. Additionally, 73% of responders required dose withholding due to keratopathy and of those, 50% had evidence of disease progression within a median of 1.2 month (range: 0.7-1.7) following BLMF interruption. DISCUSSION & CONCLUSIONS : Despite efficacy in pts with advanced MM, in routine practice, ocular toxicity of BLMF is a major challenge and a deterrent to its continuous use. While frequent ocular toxicity-related interruptions were observed at expected rates, permanent treatment discontinuation due to keratopathy was observed in a higher proportion of pts than that encountered in the DREAMM-2 trial. Larger prospective studies are warranted to accurately discern the effects of ocular toxicities on outcomes of pts treated with BLMF. Figure 1 Figure 1. Disclosures Patel: Emmecell: Consultancy; GlaxoSmithKline: Consultancy; Senju Pharmaceuticals: Consultancy; Santen, Inc.: Consultancy. Kumar: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Roche-Genentech: Consultancy, Research Funding; Carsgen: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Beigene: Consultancy; Oncopeptides: Consultancy; Antengene: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Ailawadhi: AbbVie: Consultancy; Xencor: Research Funding; Medimmune: Research Funding; Genentech: Consultancy; Ascentage: Research Funding; Takeda: Consultancy; Sanofi: Consultancy; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Cellectar: Research Funding; BMS: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Karyopharm: Consultancy; Beigene: Consultancy. Bergsagel: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: human CRBN mouse; Genetech: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Gertz: Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Kapoor: Karyopharm: Consultancy; AbbVie: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding.