Warsame, Rahma

SummaryBelantamab mafodotin (BLMF) is a B‐cell maturation antigen‐directed antibody‐drug conjugate, recently approved for advanced multiple myeloma (MM). The impact of BLMF‐induced ocular toxicity on patient outcomes is unknown. We studied a cohort of 38 consecutively seen patients treated with BLMF outside of trials. Of those, 75% experienced ocular toxicity, with 69% developing keratopathy. Among patients requiring ocular toxicity‐related permanent BLMF discontinuation (14%) or dose reduction (11%), 70% had progression of MM within a median of 3 months (95% confidence interval: 0.2–not reached) following BLMF interruption or dose reduction. Ocular toxicity is a major deterrent to the continuous use of BLMF in routine clinical practice. Measures to successfully prevent and mitigate ocular toxicity should be developed to achieve the full potential of this agent.

8022 Background: Bone marrow (BM) assessment of minimal residual disease (MRD) is being considered as a surrogate endpoint in clinical trials and is prognostic for survival in multiple myeloma (MM). Timing of BM assessment is variable across Chimeric Antigen Receptor T cell (CART) therapy trials and differs from standard of care practice. BM myeloma cell clearance can be detected by month 1 post CART, even before serum immunofixation becomes negative. BM is still hypocellular at month 1, thus prognostic value of MRD negative (MRDneg) at this timepoint is unclear. We examined impact of Day 30 MRD status in patients (pts) who received CART at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CART between 8/2016 and 6/2021. PFS and OS were plotted by Kaplan-Meier method. Results: Sixty MM pts received CART and had BM biopsy at month 1. Median age was 62 yrs, 53% were male, and 78% were BM MRDneg by flow cytometry. Baseline demographics were similar between MRDneg and MRD+ (Table). Overall, 85% (40/47) who were month 1 BM MRDneg had i/u FLC<normal. Patients who achieved CR/sCR had higher rates of BM MRDneg (100% vs 61%, p<0.001) and i/u FLC< normal (89% vs 58%, p<0.001). At month 1, 24/60 (40%) pts had hypocellular BM. Serial BM samples at month 3 (n=35), 6 (n=28) and 12 (n=23) showed MRDneg rate of 93% (25/27), 56% (9/16) 58% (7/12), respectively.. Rate of hypocellularity was 54% (19/35), 32% (9/28) and 30% (7/23), respectively. Among the MRDneg/hypocellular pts at month 1, hypocellular BM was seen in 8/11 (73%) pts at month 3 and 2/4 (50%) pts at month 6 and 12. Compared to MRD+, pts who had BM MRDneg at months1 had longer PFS (Table). PFS was not statistically significantly different between pts who had BM MRDneg and were either hypocellular or not. MRDneg pts with i/u FLC<normal at months1 had better median PFS compared to those who did not. (MRD+:2.9 months (1.2-NR). MRDneg/FLC>normal: 4.9 months (2.3-NR). vs MRDneg/FLC<normal:17.9 months (11.8-NR), p<0.0001). Conclusions: Hypocellular BM is common in the 3 months post CART. Regardless of BM cellularity, BM MRDneg at month 1 correlates with deep response and prolonged PFS. Majority of BM MRDneg pts at month 1 also had FLC<normal. BM MRDneg status and FLC normalization were associated with longer survival. Our data support the continued evaluation of BM early post CART infusion as a prognostic tool. [Table: see text]

e20001 Background: High dose melphalan followed by autologous stem cell transplant (HDM-ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) despite advances in treatments. Achievement of complete response (CR) is associated with improved overall survival (OS) and progression-free survival (PFS); Minimal Residual Disease (MRD) negativity (-) using next generation flow cytometry with a sensitivity of 10-5 is strongly associated with improved PFS and OS. We investigated the rates of conversion to MRD(-), especially MRD(-) CR following HDM-ASCT in patients with NDMM. Methods: We retrospectively reviewed patients with NDMM who underwent early HDM-ASCT at Mayo Clinic Rochester from May 2018 to July 2019. Response assessment was conducted after induction and within 100 days post-ASCT based on 2016 IMWG criteria, except for using Mass-Fix instead of immunofixation. MRD was assessed in bone marrow using the established Euro Flow protocol with sensitivity of 10-5. The FISH assay was used to risk-stratify patients as high-risk (HR) and standard risk (SR) cytogenetics as per the mSMART guidelines. Primary outcome measure was the conversion to MRD(-) CR after ASCT. Secondary outcomes include the overall conversion to MRD(-) irrespective of IMWG response, the impact of HR cytogenetics and pre-ASCT IMWG response on conversion to MRD(-) CR. Results: Two-hundred and ten patients were included; 126 (60%) were male and median age 62 years (range 32–77 years). There were 78 (44%) patients with HR cytogenetics. Pre-ASCT, 23 patients (11%) achieved MRD(-) CR, and 66 (31%) patients achieved MRD(-) CR post ASCT. Of 187 patients not in MRD(-) CR pre-ASCT, 45 (24%) converted to MRD(-) CR. Table provides a breakdown of the conversion rate of pre-ASCT IMWG response category to MRD(-) CR post ASCT and patients with MRD(+) CR had the highest rate (78%) of conversion. The presence of HR cytogenetics did not impact rates of MRD(-) CR achievement post ASCT irrespective of pre-ASCT IMWG response (p = 1.0). Overall, irrespective of IMWG response, 43 (20%) patients were MRD(-) pre-ASCT (19 in VGPR, 24 in CR or better) and 102 (49%) patients were MRD(-) post-ASCT (36 in VGPR, 66 in CR or better). Among 85 patients in VGPR post-ASCT, 36 were MRD(-) of which 8 (22%) progressed, while 49 were MRD(+) of which 24 (49%) progressed (p = 0.014). Conclusions: Upfront HDM-ASCT in patients with NDMM leads to deeper responses with 24% converting to MRD(-) CR and more than doubling of the total rate of MRD(-) irrespective of IMWG response. [Table: see text]

e18544 Background: Underrepresented minority (URM) patients continue to make up a small percentage of patients treated on cancer clinical trials (CCTs), thus perpetuating health care disparities. Research indicates that engagement of healthcare staff is critical for successful recruitment. Our study sought to better define barriers to minority recruitment to CCT from the research staff perspective. Methods: Semi-structured qualitative interviews were conducted of key stakeholders for CCT enrollment, including clinical research coordinators (CRCs), principal investigators (PIs), and treating clinicians. Questions for the healthcare team explored their experiences caring for URM patients with specific inquiry into the barriers of enrollment/retention and the processes or resources required to better meet patient needs. Results: All hematology and oncology staff at Mayo Clinic Cancer Center were invited to participate via email. Of the 28 who consented, 13 were male (46%), 15 female (54%), and 21% non-white (3 Asian, 2 Hispanic, 1 Black). Of the 19 PIs, 9 were Professors (47%), 5 Associate professors (26%), and 5 Assistant professors (26%). The additional 9 interviewees were CRCs. Select themes with representative quotes and proposed actions can be seen in Table. Conclusions: Recommendations for CCT accrual include accelerating efforts to address workforce diversity gaps, engaging in community outreach, optimization of CCT participation through collaborative care, incentivizing trial participation, and creating flexibility in eligibility criteria.[Table: see text]

e18543 Background: Representation of minority patients (pts) in cancer clinical trials (CCTs) is low and contributes to health disparities. Our study sought to understand the beliefs and motivations of minority patients and to identify barriers and facilitators of CCT enrollment. Methods: 270 minority pts treated on CCT were identified from the medical record from 2018-2021. Of the 138 of pts alive, 13 (9.4%) consented. Semi-structured qualitative interviews were conducted exploring motivations, barriers, and facilitators to CCT participation. Surveys collected demographics and explored beliefs towards cancer and factors that influenced participation. Results: Of the 13 participants, 9 were female (69%), 4 Hispanic (30%), 3 Black (23%), 3 multiple races (23%), 2 Asian (15%), 2 Native American (15%), and 1 Native Hawaiian (8%). Two pts had a high school education (15%), 7 ≥ 4-year college (54%), 4 ≥ 2-year college (30%). Eight pts were married, 3 divorced, 1 widowed, and 1 single. Employment status was: employed (4 pts, 30%), unemployed (1 pt, 8%), disabled (5 pts, 38%), retired (3 pts, 23%). All pts were insured. Median household was 3 people (range 1 to > 5); 3 pts had dependents. 9 pts had their own vehicle; 4 used public or subsidized transport. 2 pts had trouble finding transportation. Income was: 3 pts < 25K, 4 pts 25-35K, 1 pts 35-50 K, 1 pts 50-75K, and 4 pts > 75K. 4 pts received emotional support from religion. All pts had heard of CCTs and 6 (46%) had known other CT participants. Direct communication from healthcare provider was the most common way of hearing about CCT. 9 pts (69%) had trust or strong trust in experimental therapy/CCT; 4 pts (30%) were neutral. 8 pts (61%) believed standard therapy was needed to cure cancer. 5 pts (38%) believed God would decide if they die from cancer. 7 pts (54%) believed that worry makes cancer worse. Key themes about patients’ motivation to participate: chance for cure, staying positive, giving back to others, having representation in research, and advancing science. Key themes about facilitators to participation: supportive family, cost coverage for treatment, and limited treatment options. Key themes on participation: minimizing logistical barriers, decentralizing CCTs, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on purpose and benefit of CCT. Factors from survey that influenced participation are summarized in Table. Conclusions: Understanding minority pts experience through in-depth interviews is valuable and may help with recruitment.[Table: see text]

110 Background: Sarcopenia or a loss of muscle mass increases with aging and is associated with increased overall mortality in patients with cancer. Recent advances in machine learning–based CNN algorithms have allowed for the rapid processing of digital images to produce image classifications of body composition. Since incidence of MM is highly associated with aging, we sought to determine if the presence of sarcopenia, as determined by utilizing this machine learning–based CNN algorithm on CT images, had prognostic value in patients with NDMM. Methods: We identified all patients with NDMM from January 2003 to July 2019 who had a standard-dose CT scan that included the L3 vertebral level performed within 6 months of diagnosis. Using a machine learning–based CNN-algorithm, abdominal CT images were analyzed to measure muscle area. These measurements were normalized by dividing the area values by the height of the patient squared (m2) to obtain skeletal muscle index (SMI) values. Patients were categorized as sarcopenic according to international gender-specific consensus cutoffs for SMI (male: < 55 cm2/m2 and female: < 39 cm2/m2). Patients with the following FISH cytogenetics were considered high risk (HR): t(4;14), t(14;16), t(14;20), and deletion 17p/monosomy 17 whereas the remainder were standard risk (SR). Survival analysis was performed using the Kaplan-Meier method and compared via the log-rank method. Results: The study cohort consisted of 344 patients. 68 (20%) were categorized as HR based on FISH cytogenetics.187 (54%) patients were sarcopenic based on their peri-diagnosis standard-dose CT scan. Sarcopenic patients were more likely to have ISS-3 disease (45% vs. 30%; p =.023), be male (73% vs. 48%; p <.001), and be ≥ age 75 (27% vs. 14%; p =.002) compared to non-sarcopenic patients. The median OS for patients with HR FISH and ISS 2 / 3 disease was 40 months and 57 months respectively compared to 90 months and 119 months for those with SR FISH and ISS-1 disease respectively (FISH: p <.004; ISS: p <.001). The median OS for sarcopenic patients was 44 months compared to 90 months for those not sarcopenic (p <.001). The time to next therapy (TTNT) for sarcopenic patients was 39 months compared to 45 months for those not sarcopenic (p =.05). In a multivariable model, the presence of sarcopenia (HR 1.64, 95% CI, 1.05–2.56; p =.03) retained significance in the presence of HR FISH, ISS 2 / 3 disease, and age ≥ 75. Conclusions: Gender-specific sarcopenia identified by a machine learning–based CNN algorithm significantly affects OS in patients with NDMM and is independent of age, ISS stage, and cytogenetic status. Future studies utilizing this machine learning–based methodology of assessing sarcopenia in larger prospective clinical trials are required to validate these findings.

PURPOSE: Patients' concerns regarding clinical trial (CT) participation include apprehension about side effects, quality of life (QoL), financial burden, and quality of care. METHODS: We prospectively evaluated the experience of patients with multiple myeloma or lymphoma who were treated on CTs (CT group, n = 35) versus patients treated with standard approaches (non-CT group, n = 88) focusing on QoL, financial burden of care, and patients' perception of quality of care over a 1-year period. RESULTS: There were no significant differences in any of the patient-reported outcomes in CT versus non-CT groups. We observed an initial decline in overall QoL in the first 3 months across both groups, driven primarily by physical and functional well-being. QoL gradually improved and was above baseline by month 12. Patients reported highest improvement in the functional well-being subdomain. Patients in both groups reported high satisfaction with the quality of care received, and there were no differences in overall satisfaction, communication with team, or access to care. At baseline, 16%-19% of patients reported financial burden, which increased to a peak of 33% in the CT group and to 49% in the non-CT group over the course of 1 year. There was no significant difference in financial burden in the two groups overall. Most of the patients reported getting all the care that was deemed medically necessary in both groups. However, a significant proportion of patients reported having to make other kinds of financial sacrifices because of their cancer (CT group: 33% of patients at baseline and 21%-40% over 1 year; non-CT group: 19% at baseline and 25%-36% over 1 year). CONCLUSION: Patients treated on CTs reported comparable QoL and quality of care with the non-CT group. A high proportion of patients reported financial burden over time in both groups. Our findings can serve as a guide to educate patients regarding CT participation and highlight the need to address the significant financial burden experienced by patients with cancer.

Abstract Almost all patients with multiple myeloma (MM) eventually relapse, either asymptomatically or with end-organ damage. However, it remains unclear whether initiating therapy at the time of biochemical progression (BP) improves the outcomes compared with initiating therapy at the clinical progression (CP) stage. Here, we retrospectively assessed 1347 patients with relapsed MM. Most progressions were BP (60.4%); 39.6% had CP. The most prevalent symptoms at relapse were new or evolving bone disease (80.9%), anemia (38.0%), and renal failure (12.7%). Patients with BP had longer median time from second-line treatment to the next treatment compared with patients who had CP (17.0 vs 9.6 months; P &lt; .001) as well as longer median overall survival from first relapse (59.4 vs 26.2 months; P &lt; .001). Male sex (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.02-2.18; P = .04), plasma cell labeling index ≥2% (OR, 1.58; 95% CI, 1.02-2.45; P = .04), and extramedullary disease at diagnosis (OR, 1.84; 95% CI, 1.08-3.13; P = .03) were associated with higher risk of CP, whereas very good partial remission or better had decreased risk of CP (OR, 0.62; 95% CI, 0.43-0.91; P = .02). To conclude, patients with CP have inferior postprogression outcomes compared with patients who have BP. Patients with deeper response to first-line therapy are less likely to develop CP. The presence of a specific CRAB (C, hypercalcemia; R, renal failure; A, anemia; B, bone disease) symptom at diagnosis predicts for the development of similar CRAB symptoms at relapse.