Citations

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.

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]

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.

Transient insulin deprivation with concurrent hyperglucagonemia is a catabolic state that can occur in type 1 diabetes. To evaluate glucagon’s catabolic effect in the setting of its glucogenic effect, we measured the regional exchanges of amino acid metabolites (amino-metabolites) across muscle and splanchnic beds in 16 healthy humans during either somatostatin followed by glucagon or saline infusion alone. Despite a twofold or greater increase in the regional exchange of amino-metabolites by glucagon, whole-body kinetics and concentrations of amino acids (AA) remained stable. Glucagon increased the splanchnic uptake of not only gluconeogenic but also essential (EAA) AA while increasing their release from the muscle bed. Regional tracer-based kinetics and 3-methylhistidine release indicate that EAA release from muscle is likely caused by reduced protein synthesis rather than increased protein degradation. Furthermore, many metabolites known to affect insulin action and metabolism were altered by hyperglucagonemia including increase in branched-chain AA and keto acids of leucine and isoleucine in arterial plasma. Further, an increase in arterial concentrations of α-aminoadipic acid arising from increased conversion from lysine in the splanchnic bed was noted. These results demonstrate that hyperglucagonemia during hypoinsulinemia increases net muscle protein catabolism and substantially increases the exchange of amino metabolites across splanchnic and muscle beds.

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.

Background Lenalidomide is an immunomodulatory drug used to treat multiple myeloma that requires renal dosing adjustment based on Cockcroft-Gault (CG). Various equations to estimate kidney function exist and pose a potential issue with lenalidomide dosing. Objective The objective of this analysis was to evaluate the impact of estimating kidney function in newly diagnosed multiple myeloma patients with CG, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and their potential impact on lenalidomide dosing. Methods Data from 1121 multiple myeloma patients at the time of diagnosis acquired from the Mayo Clinic were used to calculate creatinine clearance (CrCl) using Cockcroft-Gault with actual body weight (CG ABW ), ideal body weight (CG IBW ), or adjusted body weight (CG AdjBW ); MDRD; and CKD-EPI for each subject. Discordances in dosing were then analyzed, and lenalidomide exposure was calculated for each subject to assess impact on pharmacokinetics of lenalidomide for patients who received discordant doses. Results Overall, approximately 16% of patients received a discordant dose when using MDRD or CKD-EPI instead of CG ABW . The most common dose discordance was the decrease of a full dose of lenalidomide 25 mg when using CG ABW down to 10 mg and when using MDRD or CKD-EPI with 53.8% to 55.6% of all discordances in this category. When assessing different body weights, the most common discordance was a decrease from 25 to 10 mg when using CG IBW instead of CG ABW ; the same trend was observed when using CG AdjBW instead as well. Patients were also at risk of over- or underexposure based on area under the concentration versus time curve (AUC) for discordant dosing. Conclusion and Relevance A significant proportion of patients are at risk of under- or overdose of lenalidomide if CKD-EPI or MDRD are used instead of CG ABW . Physicians should use CG ABW when estimating renal function to dose lenalidomide.