Visual Acuity Scale Research Articles

A comparison of self-triage tools to nurse driven triage in the emergency department.

Canadian patients presenting to the emergency department (ED) typically undergo a triage process where they are assessed by a specially trained nurse and assigned a Canadian Triage and Acuity Scale (CTAS) score, indicating their level of acuity and urgency of assessment. We sought to assess the ability of patients to self-triage themselves through use of one of two of our proprietary self-triage tools, and how this would compare with the standard nurse-driven triage process. We enrolled a convenience sample of ambulatory ED patients aged 17 years or older who presented with chief complaints of chest pain, abdominal pain, breathing problems, or musculoskeletal pain. Participants completed one, or both, of an algorithm generated self-triage (AGST) survey, or visual acuity scale (VAS) based self-triage tool which subsequently generated a CTAS score. Our primary outcome was to assess the accuracy of these tools to the CTAS score generated through the nurse-driven triage process. A total of 223 patients were included in our analysis. Of these, 32 (14.3%) presented with chest pain, 25 (11.2%) with shortness of breath, 75 (33.6%) with abdominal pain, and 91 (40.8%) with musculoskeletal pain. Of the total number of patients, 142 (47.2%) completed the AGST tool, 159 (52.8%) completed the VAS tool and 78 (25.9%) completed both tools. When compared to the nurse-driven triage standard, both the AGST and VAS tools had poor levels of agreement for each of the four presenting complaints. Self-triage through use of an AGST or VAS tool is inaccurate compared to the established standard of nurse-driven triage. Although existing literature exists which suggests that self-triage tools developed for specific subsets of complaints may be feasible, our results would suggest that adopting the self-triage approach on a broader scale for all-comers to the ED does not appear to be a viable option to enhance the current triage process. Further study is required to show if self-triage can be used in the ED to optimize the triage process.

Visualization of Keratopathy Associated With the Antibody-Drug Conjugate Belantamab Mafodotin Using Infrared Imaging in Patients With Multiple Myeloma.

The treatment of patients with relapsed/refractory multiple myeloma (RRMM) with the antibody-drug conjugate belantamab mafodotin is affected by ocular adverse effects, most frequently keratopathy with corneal microcyst-like epithelial changes (MECs). To assess ocular side effects, the "Keratopathy and Visual Acuity (KVA) scale," based on the extent of keratopathy subjectively graded on slit-lamp examination and the change in best corrected visual acuity from baseline, was created. Advanced corneal imaging techniques have been explored to further characterize MECs and identify objective imaging biomarkers. We examined whether infrared reflectance imaging of the anterior segment (AS-IR) could contribute to the assessment, monitoring, and documentation of corneal toxicity in patients treated with belantamab mafodotin. In addition to the KVA examination, AS-IR imaging was performed. AS-IR images were evaluated for presence of visible hyporeflective lesions and their spatial and temporal distribution between visits and compared with keratopathy identified on slit-lamp examination. To standardize the assessment, a scoring system for lesions on AS-IR was implemented for additional analysis. Nine patients undergoing treatment with belantamab mafodotin for up to 9 months were examined. All patients exhibited hyporeflective lesions on AS-IR imaging, indicative of corneal toxicity corresponding to MECs observed on slit-lamp examination. AS-IR lesions showed early occurrence, variable quantity and size, and distinct distribution patterns, correlating with clinical findings during treatment. As shown for belantamab mafodotin, AS-IR imaging represents a fast, noninvasive, supplemental method for documentation, monitoring, and assessment of corneal adverse effects during treatment with antibody-drug conjugates, which may enable more standardized analyses.

Clubfoot Correction with Ponseti Technique: Three-Dimensional Alignment Analysis and Residual Adult Deformity Effects on Patient-Reported Outcomes

Introduction/Purpose: Few studies have assessed the long-term outcomes of the Ponseti technique and none have utilized 3- dimensional weightbearing analysis. The goal of this study was to understand how potential residual 3D deformities and abnormalities influence patient reported outcomes (PROs). This was accomplished by assessing anatomical foot and ankle alignment in adult clubfoot patients treated with the Ponseti method using 3D weightbearing CT (WBCT) imaging and then correlating residual foot and ankle malalignment with PROs. Methods: There were 37 consecutive patients (57 feet) included and 14 volunteers healthy controls (28 feet) included in this study. Every participant was evaluated using a WBCT (HiRise©) in a bipedal standing position. From these scans Cavus, Adductus, and Varus components were evaluated using multiple 3D measurements calculated using the semi-automatic segmentation software Bonelogic®. Specific Cavus related measurements included sagittal talus-first metatarsal angle and the calcaneal inclination angle. Varus related measurements included talocalcaneal angle in both the sagittal and axial planes as well as the hindfoot moment arm and the hindfoot alignment angle. Adductus deformity was evaluated using talonavicular coverage angle. These measurements were then correlated with patient reported outcome surveys, which included Visual Acuity Scale for pain, PROMIS general health, PROMIS physical function, PROMIS pain interference, pain catastrophic scale, and European foot and ankle society score. Results: There was no significant overall residual 3D-deformity observed in clubfoot patients when compared to controls, with similar FAO measurements observed between the groups, clubfoot=2.63% (95%CI=1.41%-3.85%) and control=3.2% (CI=1.6%- 4.8%,P=0.58). The sagittal talus-first-metatarsal in the clubfoot-patients had a mean-value of -0.12° compared to the controls, −5.2°. Clubfoot patients also had a decreased calcaneal-inclination-angle relative to the controls, 13.01° and 21.5° respectively. Talocalcaneal-angle for clubfoot patients in both the sagittal-plane,44.28°, and axial-plane, 17.74°, were reduced compared to the controls, 57.51° and 25.78°. Talonavicular-coverage-angle in the clubfoot-group (18.63°) was less than the controls (29.19°). Talus- first-metatarsal-angle in the sagittal-plane was significantly correlated with VAS-scores (RSquare=0.19,P=0.0118) and the EFAS- Score (RSquare=0.27,P=0.0025). Talocalcaneal-angle in the sagittal plane was also significantly correlated with the PROMIS-Pain- Interference-score (P=0.038) and PROMIS-Physical-Function-score (RSquare=0.32,P=0.0007). Conclusion: The Ponseti technique is an effective nonsurgical treatment for the overall three-dimensional foot and ankle alignment of Clubfoot. While mild, but statistically significant residual Varus and Adductus deformities were observed in adult clubfoot patients, the overall 3D alignment (FAO) was found to be similar between clubfoot patients and controls. These findings highlight the efficacy of the Ponseti technique and potentially explain the overall good PROs. The results of this study could potentially provide insight into treatment targets that may be applied to help optimize patient outcomes when treating children with Clubfoot in the future. The Ponseti technique is an effective nonsurgical treatment for Clubfoot's overall three-dimensional foot and ankle alignment. While mild, but statistically significant residual Varus and Adductus deformities were observed in adult clubfoot patients, the overall 3D alignment (FAO) was found to be similar between clubfoot patients and controls. These findings highlight the efficacy of the Ponseti technique and potentially explain the overall good PROs. The results of this study could potentially provide insight into treatment targets that may be applied to help optimize patient outcomes when treating children with Clubfoot in the future.

Prevention of Ocular Toxicity Using Protective Contact Lenses in Multiple Myeloma Patients Receiving Belantamab Mafodotin, Pomalidomide and Dexamethasone: A Sub-Study of the Cmrg-007 Trial

Background: Belantamab mafodotin (belamaf) is a monomethyl auristatin-F containing antibody drug conjugate that targets BMCA on myeloma cells. Single agent belamaf has shown clinical meaningful activity in relapsed/refractory multiple myeloma (RRMM) but ocular adverse events (AEs) affect 53-72% of trials'participants. In DREAMM-2, prophylactic corticosteroid eye drops did not effectively reduce the risk of keratopathy. It is therefore imperative that strategies to mitigate corneal AEs be explored. This 2-part study is designed to evaluate belamaf and pomalidomide/dexamethasone (Pd) in RRMM. Here we report the efficacy and ocular AEs of patients (pts) receiving 2.5 mg/kg (maximum tolerated dose) or 1.92 mg/kg IV belamaf and administrated on various schedules aimed to define the optimal balance of efficacy and tolerability. We also present results of an ocular sub-study exploring the use of bandage contact lens (BCLs) to reduce the risk and severity of belamaf-associated ocular AEs. Methods: Eligibility: > 1 prior lines of therapy (LoT), lenalidomide, proteasome inhibitors exposed, and refractory to the last LoT. Pd was administered per standard of care and belamaf (1.92 or 2.5 mg/kg) Q4W or 2.5 mg/kg Q8W, Q12W or SPLIT equally on days 1 and 8, Q4W. Pts enrolled on the ocular sub-study received the recommended part two dose (RP2D): 2.5 mg /kg Q8W. A BCL (Bausch and Lomb Pure Vision) was placed in the right (R) eye for the 1st 2 doses of belamaf with the left (L) eye serving as control. Subsequently, BCLs were placed in both eyes. Pts wore BCLs for up to 28 days after each belamaf dose. Evaluation by an eyecare specialist for a comprehensive eye exam and BCL placement occurred every 15-28 days during BCLs use and prior to each belamaf dose. Corneal findings were graded (Gr) by the keratopathy and visual acuity (KVA) scale and findings of local infection were reported. Keratitis prophylaxis during BCLs use included gatifloxacin 0.3% or tobramycin 1.3% eye drops. Results: This analysis comprises 92 pts including 14 on the ocular sub-study. Baseline best corrected visual acuity (BCVA) and ocular comorbidities were similar across all cohorts: with median 20/20 BCVA 46.7% R and 50% L eye. Abnormal fundoscopy was 21.7% in R and 16.3% in L eye. There was a trend to lower incidence and less severity of ocular AEs for the 1.92 mg/kg dose (Table 1). Gr 3-4 keratopathy, decrease in BCVA and subjective Gr >2 blurred vision by CTCAE were 33.3% (4/12), 41.7% (5/12) and 25% (3/12) for the 1.92 mg/kg and 75% (9/12), 75% (9/12) and 33.3% (4/12) for 2.5 mg/kg Q4W cohorts. Preliminary data indicated superior clinical efficacy (ORR, >VGPR rate and mPFS) for the 2.5 mg/kg dose, 100% (12/12), 91.7% (11/12) and 25.1 months (11.8-NYR) versus 66.7% (8/12), 63.6% (7/12) and 16.9 months (5.3-19.7) for the 1.92 mg/kg dose (Table 2). To preserve efficacy but reduce ocular AEs additional cohorts exploring 2.5 mg/kg dosed every 8 and 12 weeks were included. Extended dosing schedules showed lower rates of Gr 3-4 keratopathy, decrease in BCVA, and Gr ≥2 blurred vision: 58.3% (7/12), 91.7% (11/12) and 16.7% (2/12) of pts treated Q8W; and 58.3%, 58.3% and 16.7% (2/12) of pts treated Q12W versus the Q4W schedule. Importantly, the efficacy was preserved with ORRs of 91.7% (11/12) and 100% (11/11), >VGPR rates of 83.3% (10/12) and 63.6% (7/11) and mPFS of 18.3 months (95% CI: 10.1-NYR) and 22.5 (95% CI: 8.9-NYR) for Q8W and Q12W groups, respectively. In the ocular sub-study, assessment of R and L eye during the first 2 belamaf doses showed a significant delay in onset of BCVA decrease in the R eye (p<0.0001) compared to the L. Comparing pts treated at the RP2D, moderate to severe (Gr ≥2) keratopathy and decrease BCVA were significantly lower (p=0.0004 and 0.010), in the BCL cohort versus no-BCL group. Further there was a trend towards less symptomatic blurred vision (p=0.256). BCL pts were able to complete 90% of the pre-planned belamaf cycles compared to 70% in the RP2D no-BCL group (p=0.029). No cases of infectious keratitis were reported in the BCL cohort. Conclusions: Our data suggest that extended dosing intervals may be a significant step forward in mitigating corneal AEs of belamaf. This preliminary report on the efficacy of BCLs in 14 pts demonstrates a decrease in moderate to severe corneal AEs and reduction in dose holds for corneal AEs, noting however a short follow up at this time. The data support the further evaluation of BCLs in preventing belamaf associated ocular toxicities.

Impact of Long-Term Treatment with Belantamab Mafodotin on Safety and Efficacy Outcomes in Patients with Relapsed/Refractory Multiple Myeloma in DREAMM-3

Introduction: DREAMM-3 (NCT04162210) is a randomized study comparing single-agent belantamab mafodotin, a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, to a standard-of-care regimen, pomalidomide plus dexamethasone (Pd). This post-hoc analysis from the DREAMM-3 trial evaluated the safety and efficacy of long-term treatment (≥52 weeks) with belantamab mafodotin compared with Pd, as well as the effects of dose modifications, in adult patients with relapsed/refractory multiple myeloma (RRMM) at third line of therapy or later. Methods: Patients were randomized (2:1) to belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks (Q3W; 21-day cycle) or pomalidomide 4 mg orally once daily (Days 1-21) and dexamethasone 40 mg (20 mg if >75 years) orally once weekly (28-day cycle). Belantamab mafodotin dose reductions or delays were permitted to manage treatment-related Grade 3-4 adverse events (AEs), or Grade 2 AEs that were worsening or had symptoms lasting >7 days. Following AE resolution to Grade ≤1, belantamab mafodotin treatment could resume with or without dose reduction (to 1.9 mg/kg). If no dose delays occurred, patients could receive a maximum of 17 cycles in 52 weeks, hence 17 cycles was used as a threshold to assess long term safety. Ocular exams were performed prior to dosing belantamab mafodotin Q3W up to Cycle 6, then every 3 months if no significant ocular events were reported. Treatment-related ocular AEs were graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5 and per the Keratopathy Visual Acuity (KVA) scale. The KVA scale incorporates corneal examination findings and changes in Snellen-equivalent best corrected visual acuity (BCVA) into a composite grade. Ocular AEs are reported as worst-case post-baseline. Efficacy responses (per 2016 International Myeloma Working Group criteria) were assessed Q3W, regardless of treatment delays. Results: As of September 12, 2022, 50/218 (23%) patients were treated with belantamab mafodotin for ≥52 weeks. AEs were reported in all patients treated with belantamab mafodotin for ≥52 weeks. Grade ≥3 AEs occurred in 82% (n=41); the most frequent were reduced visual acuity (24%), thrombocytopenia (18%), and neutropenia (16%). The majority of AEs reported occurred at or before cycle 17. For the most common (>40%) AEs (any grade), few additional events occurred after cycle 17 (1 new occurrence each of dry eye, reduced visual acuity, eye irritation, and thrombocytopenia after cycle 17). Few infections (any grade) occurred after cycle 17 (COVID-19, n=5; viral infection, n=1; pneumonia influenzal, n=1). No patients permanently discontinued treatment due to AEs considered related to belantamab mafodotin. Ocular AEs were reported in 94% (n=47) of patients treated with belantamab mafodotin for ≥52 weeks. The majority of ocular AEs (n=487) were of Grade 1 or 2 severity (88%) and no ocular AEs led to study treatment discontinuation. At the time of data cutoff, 95% (n=41) of patients experiencing Grade ≥2 KVA events had recovered prior to the end of study treatment exposure (defined as last dose + 20 days). Most patients had a dose modification, and no loss of efficacy was observed. The clinical benefit rate (≥minimal response) in these patients was 90% (45/50) and the median time to best response was 6.3 months (range 0.8-18.8). Median duration of response was not reached (NR; 95% CI 17.9, NR) in the subset of patients treated for ≥52 weeks. At the time of data cutoff, 94% (n=47) patients were alive. Conclusions: In patients who received long-term treatment (≥52 weeks), the safety profile of belantamab mafodotin was consistent with previous reports. Despite the need for belantamab mafodotin dose delays and reductions, no patients discontinued study treatment due to belantamab mafodotin-related AEs. During dose delays, clinical responses were maintained or deepened in most cases, demonstrating that management of AEs using dose modifications did not impact clinical activity. Together, this suggests that dose modifications are highly effective in the management of emerging AEs while allowing for sustained clinical benefit. Funding: GSK (207495). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Evaluation of a Novel Method for the Assessment of Ocular Adverse Events and Associated Functional Impact in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial

Introduction Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen, has shown promising efficacy and a favorable tolerability profile in the treatment of multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. Keratopathy and Visual Acuity (KVA) scale was used in most belamaf trials, including the pivotal DREAMM-2, to guide belamaf dose modifications. KVA grading is dependent on an ophthalmologist consultation prior to belamaf administration. Herein, we evaluate a novel approach to guide belamaf dosing in transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Part 1 evaluated the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and established that the recommended phase 2 dose (RP2D) is 1.9 mg/kg, initially administered q8w and, depending on toxicity, adjusted to q12w. Part 2 investigates the safety/efficacy of RP2D in Groups A and B, comprised of 15 pts each, and evaluates two different sets of guidelines for the management of OAEs. In Group A, belamaf dosing is guided by the KVA scale; in Group B, dose modifications are determined by the pts' responses on ocular symptoms and their impact on activities of daily living (ADL), captured by the Vision Related Anamnestic (VRA) tool, and by the presence of ≥Grade (Gr) 3 KVA events (BCVA reduced/corneal findings). VRA is a novel, 9-item physician administered questionnaire designed to assess the frequency of ocular symptoms and their impact on vision-related activities. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation, while ocular symptoms are classified by CTCAE v5.0. Herein, we present the OAEs and the clinical activity of the treatment combination for both Groups of Part 2 (cut-off date 05/06/2023). Results By the cut-off date, twenty-four pts [median age: 75.5 years; male: 16 (66.7%)] had received ≥ 1 belamaf dose in Part 2 and were still on treatment. At baseline, most pts had ocular comorbidities. The median belamaf administrations and number of cycles reached were 3.0/2.0 and 6.5/5.5, for Groups A and B, respectively. A meaningful BCVA decline (BCVA <20/50) with at least 3 lines drop in the better seeing eye, was noted in 5/52 (9.6%) and 5/45 (11.1%) assessments, while BCVA ≤20/200 with at least 3 lines drop was noted in 1/59 (1.7%) and 2/51 (3.9%), respectively. Overall, no ≥Gr 3 ocular symptoms were observed, while the most frequent ≥Gr 2 ocular symptom was dry eye (57/110, 51.8%); also, no ≥Gr3 keratopathies were recorded. Among 66/59 VRA assessments, ocular symptoms and ADL impairment, manifesting for >50% of the time (substantial time) in the last 24 hours prior to belamaf administration, were noted in 2 (3.0%)/9 (15.3%) and 2 (3.0%)/7 (11.9%), respectively. Importantly, numerically similar proportions of KVA events and skipped belamaf doses were noted in both Groups (Table 1). Furthermore, although the sample size of the present analysis does not allow conclusions for the VRA test characteristics, it is notable that in all assessments where eyesight difficulties were reported for substantial time, ≥Gr2 KVA events were also recorded, suggesting a potential association between VRA responses and KVA events, that warrants further investigation. Finally, in terms of clinical activity, for the 19 response-evaluable pts (≥2 efficacy assessments), at a median follow-up of 7.4 months the ORR was 90%/100% in Groups A and B (PR/VGPR: 30%/60%; 66.7%/33.3%) with no disease progression observed. Conclusions In this preliminary descriptive analysis, the VRA tool was safe and effective in informing belamaf dose adjustments in the extended dosing schedule. Recruitment in Part 2 is ongoing and, as data accumulates, future analyses will provide further insight on the potential association of the VRA tool with KVA events, which may eliminate the need for an ophthalmic exam prior to belamaf dosing.

An Updated Analysis of Ocular Adverse Events and Vision-Related Functioning in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial

Introduction Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. In this descriptive analysis, we evaluate the OAEs and their impact on daily functioning in transplant ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. The study is comprised of 2 Parts: Part 1 evaluates the safety/clinical activity of three different belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd and establishes the recommended phase 2 dose (RP2D). Part 2 further investigates the safety/efficacy of RP2D in two Groups and evaluates two different sets of guidelines for the management of OAEs. In Part 1, belamaf is initially administered q8w and, depending on toxicity, dosing may be adjusted to q12w. Ocular assessments include best corrected visual acuity (BCVA), using Snellen chart and manifest refraction, and corneal exam using slit lamp microscopy. Ocular symptoms are classified by Common Terminology Criteria for Adverse Events v5.0, while dry eye disease severity and vision-related functioning is assessed with the patient-reported questionnaire Ocular Surface Disease Index (OSDI). In Part 1 of the study, severity of corneal events is assessed with the Keratopathy Visual Acuity scale. This descriptive analysis presents the OAEs in all Part 1 pts over an extensive follow-up period (data cut-off: 05 June 2023). Results Thirty-six pts were included in this analysis, who were followed up for a median of 20.3 months (range 3.2-26.8). At baseline, all pts had ocular comorbidities. Among 216/244/201 BCVA assessments in cohorts 2.5/1.9/1.4 mg/kg, a meaningful BCVA decline (BCVA <20/50) with at least 3 lines drop in the better seeing eye, was observed in 21 (10%)/24 (10%)/17 (8%) of the assessments, while BCVA ≤20/200 with at least 3 lines drop in the better seeing eye was noted in only 2 (1%)/3 (1%)/8 (4%), with a median time to resolution of 1 month. The most frequently reported ≥Gr 3 ocular symptom was decreased vision, observed in 11 (5%)/ 8 (3%)/ 7 (3%) of the assessments, while ≥Gr3 keratopathy was noted in < 2% of assessments across all cohorts. Regarding OSDI, from 202/234/196 responses received, the number of “all/most” of the time worst responses in the ocular symptoms category were 6 (3%)/6 (3%)/8 (4%), while the respective proportions in the Activities of Daily Living category (ADL) were 6 (3%)/4 (2%)/3 (2%). In terms of missed doses due to OAEs, among 129/138/119 planned belamaf infusions, the number of skipped doses were 53 (41%)/48 (35%)/32 (27%). The overall response rate was 100%, no disease progression was observed over a median follow-up of 20.3 months, and 30 (83%) patients achieved at least VGPR while 19 (53%) achieved at least CR, with a median time to first response of 1 month. Conclusions Over a prolonged follow-up period, the belamaf-Rd triplet, with the extended dosing schedule for belamaf, had a minimal impact in vision-related functioning, as the ‘all/most’ of the time worst answers in the ADL category of OSDI was ≤3% across all cohorts. Furthermore, the frequency of clinically relevant impairment in vision was low, as a meaningful BCVA decline was observed in <10% of assessments, with a rapid time to resolution. Finally, the treatment combination induced rapid, deep and durable responses across all dose levels, with no PD observed. In conclusion, this novel extended belamaf schedule nearly eradicates the risk for clinically relevant ocular toxicity and impact on ADL, without any compromise in clinical activity, suggesting it may be a valid option in the upfront treatment of this frail, elderly and difficult-to-treat pt population.

Patients with operative gluteus medius tears often present with a concomitant history of lumbar pathology

BackgroundStudies have indicated a correlation between patients presenting with decreased gluteus medius function and a history of lumbar pathology (LP). However, literature investigating the relationship between the prevalence of lumbar pathology in patients with gluteus medius tears is lacking. The purpose of this study is to determine if patients undergoing repair for gluteus medius tears have concomitant lumbar pathology. Materials and methodsPatients aged 18–80 who underwent endoscopic gluteus medius repair by one fellowship-trained surgeon between May 2016 and May 2020 for peritrochanteric pain/tenderness, abductor weakness, and MRI findings consistent with a gluteus medius tear were identified. Pre-operative and post-operative data were gathered using the Visual Acuity Scale (VAS), and post-operative data was gathered using the Abbreviated International Hip Outcome Tool (iHOT-12) and Hip Outcome Score – Activities of Daily Living (HOS-ADL). Outcomes were compared between patients with and without a history of lumbar pathology. ResultsOf 23 hips, 19 (82.6%) presented with a prior history of lumbar pathology. Twenty (87.0%) patients identified were female. A total of 19 hips were included with completed PROM scores. Patients with lumbar pathology had similar pre and post-operative patient reported outcomes. ConclusionsThis study demonstrates a high incidence of lumbar pathology in patients presenting for operative gluteus medius tears, which may suggest an association between lumbar disease and the development of gluteus medius weakness and tears.

A Phase I/II Single Arm Study of Belantamab Mafodotin, Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: Planned Interim Analysis of Safety and Efficacy. Amarc 19-02 Belacard Study

Introduction Belantamab Mafodotin (Belamaf, B), a first in class anti-B-cell maturation antigen (BCMA) antibody-drug conjugate, is efficacious in triple-class exposed, relapsed and refractory multiple myeloma (RRMM). Combination therapy with carfilzomib and dexamethasone (Kd) is potentially synergistic through different anti-myeloma mechanisms of action. We report here a planned interim analysis of safety and responses after the first two cycles of combination therapy. Methods BelaCarD is an ongoing, single-arm, multicentre phase I/II study evaluating 8-weekly B dosing schedule in combination with Kd in patients (pts) with RRMM after 1-3 lines of therapy. B (2.5mg/kg) was administered intravenously (IV) on day (D)1 of every second 28D cycle; K 70mg/m2 IV D1 (20mg/m2 on C1D1), D8 and D15 of every cycle and dexamethasone 40mg weekly (20mg/m2 for pts >75 years). Treatment was continued until disease progression. Corneal adverse events (AEs) were graded as per the keratopathy and visual acuity (KVA) scale and all other AEs as per CTCAEv5. Confidence interval coefficients for response rates (RR) were adjusted using an alpha-spending function. The primary objective is progression free survival (PFS). Results As of 13 th July 2023, 65 pts (67% male) of the intended 70 have been enrolled. 55 pts (62% male) received minimum 2 cycles of B-Kd and were included in the protocol-specified interim analysis. The median age was 69.7 years (48-81); 18 pts (33%) had high-risk cytogenetics either at diagnosis or screening. ISS stage I, II, III occurred in 47.3%, 23.6% and 10% respectively. 25.5%, 38.2% and 34.6% pts had 1, 2 and 3 prior lines of therapy respectively including (exposed/refractory) bortezomib (90.9%/42%), K (3.6%/50%), lenalidomide (52.7%/44.8%), pomalidomide (5.5%/33%), anti-CD38 monoclonal Ab (mAb) (30.9%/52.9%), autologous stem cell transplant (ASCT) (41.8%). The median number of cycles received was 9 (2-27). Treatment-related AEs were reported in 93% of pts (Gr3 60%, Gr4 13%); most frequent were (all grade, Gr3, Gr4): blurred vision (40%, 7.3%, 0%), nausea/vomiting (29.1%, 3.6%, 0%), insomnia (23.6%, 10.9%, 0%), thrombocytopenia (23.6%, 10.9%, 5.5%). Ocular AEs occurred in 42 (79.2%) out of 53 evaluable pts including decline in best corrected visual acuity (BCVA) (total 77.2%, Gr1 9.4%, Gr2 33.9%, Gr3 33.9%) and keratopathy (K) (total 75.4%, Gr1 5.6%, Gr2 22.6%, Gr3 47.2%). Median time to reach worst-grade BCVA and K was 106 (25-309) and 76.5 (25-231) days respectively. Median time to return to Gr ≤1 BCVA and K was 61 (28-322) and 94 (30-326) days respectively. Ten pts had B-related SAEs (Gr 1/2 n=2, Gr 3 n=6, Gr 4 n=1, one pt died of sepsis). A second treatment-related death was due to pneumonia. Six pts discontinued therapy due to treatment-related AE including 4 due to B (corneal toxicity n=2, sepsis n=1, proteinuria n=1). Overall RR and ≥ VGPR by end of cycle 2 were 80% (97%CI: 65.3 - 90.5) and 40% (97%CI: 25.5 - 55.9) respectively. At estimated median potential follow-up of 13 months (4-38), the preliminary estimate of PFS at 24m was 56.1%. Conclusion B-Kd with an extended B schedule demonstrates a manageable safety profile. The preliminary efficacy data is encouraging with deep responses observed after only 2 cycles of therapy. Recruitment is close to completion with the main analysis to be conducted once all pts have completed the 12-month assessment. Acknowledgement: pts, their families and participating AMaRC members and sites as well as the support of GSK and funding support from the Victorian Cancer Agency.

Longitudinal efficacy and safety modeling and simulation framework to aid dose selection of belantamab mafodotin for patients with multiple myeloma.

Belantamab mafodotin, a monomethyl auristatin F (MMAF)-containing monoclonal antibody-drug conjugate (ADC), demonstrated deep and durable responses in the DRiving Excellence in Approaches to Multiple Myeloma (DREAMM)-1 and pivotal DREAMM-2 studies in patients with relapsed/refractory multiple myeloma. As with other MMAF-containing ADCs, ocular adverse events were observed. To predict the effects of belantamab mafodotin dosing regimens and dose-modification strategies on efficacy and ocular safety end points, DREAMM-1 and DREAMM-2 data across a range of doses were used to develop an integrated simulation framework incorporating two separate longitudinal models and the published population pharmacokinetic model. A concentration-driven tumor growth inhibition model described the time course of serum M-protein concentration, a measure of treatment response, whereas a discrete time Markov model described the time course of ocular events graded with the GSK Keratopathy and Visual Acuity scale. Significant covariates included baseline β2 -microglobulin on growth rate, baseline M-protein on kill rate, extramedullary disease on the effect compartment rate constant, and baseline soluble B cell maturation antigen on maximal effect. Efficacy and safety end points were simulated for various doses with dosing intervals of 1, 3, 6, and 9 weeks and various event-driven dose-modification strategies. Simulations predicted that lower doses and longer dosing intervals were associated with lower probability and lower overall time with Grade 3+ and Grade 2+ ocular events compared with the reference regimen (2.5 mg/kg every 3 weeks), with a less-than-proportional reduction in efficacy. The predicted improved benefit-risk profiles of certain dosing schedules and dose modifications from this integrated framework has informed trial designs for belantamab mafodotin, supporting dose-optimization strategies.

Impact of Routinely Performed Optical Coherence Tomography Examinations on Quality of Life in Patients with Retinal Diseases-Results from the ALBATROS Data Collection.

An observational cohort study included patients with retinal diseases starting an intravitreal anti-vascular endothelial growth factor treatment in Germany. Treatment followed clinical practice except mandatory OCT examination during the 12-month observation period. VRQoL was assessed by NEI VFQ-25 and compared with respect to OCT examinations and number of intravitreal injections in the different diseases (nAMD, DME, BRVO, CRVO). 1478 patients (74.5 ± 10.9 years, 54.9% female) were included in the analysis. Patients had neovascular AMD (65.2%), DME (18.4%), BRVO (9.5%), or CRVO (6.9%). 8.8 ± 2.6 OCT examinations and 6.1 ± 3.2 intravitreal injections were performed within 12 months. VRQoL differed between indications at baseline, with substantially lower values for neovascular AMD and CRVO. After twelve months, an increase in visual acuity and visual functional scale was observed for nAMD, DME, and BRVO, while in DME only, there was an association between number of OCT examinations and VRQoL. Intravitreal treatment was able to maintain VRQoL over twelve months in a real-world setting. Regular OCT examinations were associated with higher gain in VRQoL in DME patients after 12 months.

MonumenTAL-5: A Phase 3 Study of Talquetamab Versus Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma Who Received ≥4 Prior Lines of Therapy, Including a Proteasome Inhibitor, an Immunomodulatory Drug, and an Anti-CD38 Monoclonal Antibody

Background: Despite multiple therapeutic options for patients with multiple myeloma (MM), clonal heterogeneity and acquired resistance lead to relapse and disease which is refractory to existing treatments in almost all patients. Patients with relapsed or refractory MM (RRMM) whose disease progresses after receiving standard therapies such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs) are challenging to treat, and new, effective treatment options are needed. Belantamab mafodotin (belantamab) is approved as a monotherapy for patients with RRMM who have previously progressed after 4 prior lines of therapy (LOT), including a PI, an IMiD, and an anti-CD38 mAb; however, disease control remains suboptimal, with response rates of ~30% and a median progression-free survival (PFS) of 2.9 months. There is an unmet need for new, accessible and efficacious therapeutic options with different mechanisms of action that can provide deeper, more sustained responses. Talquetamab is a first-in-class, off-the-shelf, T-cell redirecting, bispecific antibody targeting both G protein-coupled receptor family C group 5 member D (GPRC5D) and CD3. In the phase 1/2 MonumenTAL-1 study (NCT03399799), talquetamab monotherapy had a manageable safety profile and showed encouraging efficacy in heavily pretreated patients with RRMM. MonumenTAL-1 was a single-arm trial and did not include a comparator, so there is a need for direct comparisons between talquetamab and other approved therapies in this heavily-pretreated patient population. The phase 3, multicenter, randomized, open-label, active-controlled MonumenTAL-5 trial will compare the efficacy and safety of talquetamab monotherapy with belantamab in patients with RRMM with ≥4 prior LOT. Study Design and Methods: Eligible patients include those ≥18 years of age with documented MM per International Myeloma Working Group (IMWG) criteria, measurable disease, Eastern Cooperative Oncology Group performance status 0-2, who received ≥4 prior LOTs (including at least one PI, one IMiD, and an anti-CD38 mAb), and have progressive disease on or after their last regimen. Patients with prior GPRC5D-directed treatment or belantamab will be excluded. Approximately 216 patients will be randomized 1:1 to receive 42-day cycles of subcutaneous talquetamab (0.8 mg/kg every other week) or intravenous belantamab (2.5 mg/kg every 3 weeks), stratified by International Staging System stage (I/II vs III), number of prior therapies (4 vs >4), and prior BCMA-targeted therapies (naive vs exposed). Step-up doses of talquetamab will be administered before the first full dose of talquetamab in Cycle 1. Patients will receive treatment until disease progression, start of subsequent antimyeloma therapy, death, intolerable toxicity, withdrawal of consent, or end of study, whichever occurs first. The dual primary endpoints are PFS and overall response rate (ORR); response will be assessed per 2016 IMWG criteria as adjudicated by an IRC. Secondary endpoints include very good partial response or better rate, complete response or better rate, overall survival (OS), PFS on next LOT (PFS2), patient-reported outcomes, and incidence and severity of adverse events (AEs). Exploratory endpoints include the rate of minimal residual disease negativity. AEs will be graded by Common Terminology Criteria for AEs v5.0, except for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which will be graded by American Society for Transplantation and Cellular Therapy guidelines, and corneal AEs, which will be graded according to the Keratopathy and Visual Acuity scale. The study will end when ~160 OS events have been observed across both arms. The study will open for enrollment in October 2022. Results from this study will provide insights into the efficacy and safety of talquetamab monotherapy compared with belantamab in heavily pretreated patients with RRMM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Single-Agent Belantamab Mafodotin in Patients with Relapsed or Refractory Multiple Myeloma: Final Analysis of the DREAMM-2 Trial

Introduction: Belantamab mafodotin (belamaf) is a first-in-class, B-cell maturation antigen-binding antibody-drug conjugate containing monomethyl auristatin F. Belamaf eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma immune response. In the primary1 and 13-month follow-up2 DREAMM-2 study analyses in patients with RRMM, belamaf monotherapy demonstrated deep and durable responses, with a manageable safety profile. The aim of this report is to analyze the efficacy/safety profile of belamaf using final data from the pivotal DREAMM-2 study. Methods: DREAMM-2 (NCT03525678) is a Phase 2, 2-arm, open-label study of single-agent belamaf in patients with triple-refractory RRMM who had ≥3 prior therapies and were refractory to an immunomodulatory agent, and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 mAb. Belamaf doses evaluated were 2.5 and 3.4 mg/kg every 3 weeks (Q3W). The primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, ocular symptoms, and health-related quality of life. Eye exams, including a corneal exam and assessment of change in best corrected visual acuity (BCVA), were conducted at baseline and prior to each dose. The GSK Keratopathy and Visual Acuity scale was used for grading ocular events. Recovery was defined as Grade 1 exam findings/no exam findings, and ≤1-line decline in BCVA vs baseline. Ocular symptoms were graded per CTCAE version 4.03. Patients completed patient-reported outcomes questionnaires during treatment at baseline and Q3/6W. Results: At the cutoff date (31Mar22), the median duration of follow-up for patients randomized to the belamaf 2.5 mg/kg cohort (N=97) was 12.48 months (range 0.1-40.4), and 13.77 (0.1-42.8) months for patients randomized to the 3.4 mg/kg cohort (N=99) (Table). The ORR in the 2.5 mg/kg and 3.4 mg/kg groups was 32% and 35%, respectively; 19% and 24% of patients (58% and 69% of responders) achieved very good partial response (VGPR) or better. Median time to response was 1.5 months (95% CI 1.0, 2.1) in the 2.5 mg/kg cohort and 1.4 months (0.9, 2.1) in the 3.4 mg/kg cohort. The MRD negativity rate of patients with ≥VGPR was 36% and 23% for the 2.5 and 3.4 mg/kg cohorts. Median duration of response was 12.5 and 6.2 months for the 2.5 and 3.4 mg/kg cohorts. Median PFS was 2.8 and 3.9 months. Median Kaplan-Meier estimated OS was 15.3 and 14.0 months. In patients who achieved ≥VGPR, median PFS was 14.0 and 16.8 months for the 2.5 and 3.4 mg/kg cohorts, respectively. In patients who achieved ≥VGPR, estimated OS was 30.7 and 35.5 months. The 3 most common Grade ≥3 adverse events (AEs) were keratopathy, anemia, and thrombocytopenia (Table). AE-related dose reductions occurred in 36% and 44%, dose delays occurred in 54% and 62%, and AE-related permanent discontinuations occurred in 9% and 5% for the 2.5 and 3.4 mg/kg cohorts, respectively; discontinuation due to ocular events was rare (3% in both cohorts). The most commonly reported ocular events in the 2.5 mg/kg cohort included keratopathy (71%), blurred vision (23%), BCVA reduced to 20/50 (21%), and dry eye (15%). BCVA changes and blurred vision were transient; up to 86% of all patients who had experienced blurred vision or worsening BCVA had resolution by the end of follow up. No permanent complete vision loss occurred. Despite changes in BCVA and blurred vision, EORTC-QLQ-C30 data suggest that overall Global Health Status/QoL, Physical and Role functioning, and overall disease symptoms were maintained or improved during treatment. Conclusions: This final analysis of DREAMM-2 confirms earlier reports1,2 that single-agent belamaf (2.5 mg/kg and 3.4 mg/kg) results in rapid, deep, durable, and clinically meaningful responses with a manageable safety profile in patients with RRMM. No new safety signals were observed. Dose modification remained effective in resolving ocular events and allowed patients the clinical benefit gained from continuing treatment with belamaf. Patient quality of life was maintained or improved despite changes in ocular symptoms. 1. Lonial S, et al. Lancet Oncol. 2020;21:207-21; 2. Lonial S, et al. Cancer. 2021;127:4198-212. Funding: GSK (Study 205678). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone Demonstrates Durable Responses in Triple Class Exposed/Refractory Multiple Myeloma

Background: Belantamab mafodotin (belamaf) is a first-in-class antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA). Belamaf has shown clinically meaningful activity as a single agent in relapse/refractory multiple myeloma (RRMM). The Algonquin study demonstrated that the anti-myeloma activities of belamaf are significantly increased by the immunomodulatory drug pomalidomide (POM). The Algonquin study is a two part study designed to evaluate the safety and efficacy of different doses and schedules of belamaf in combination with POM and dexamethasone (DEX) (Bela-Pd) in patients (pts) with RRMM. Here we report updated safety and efficacy data for the subgroup of RRMM pts exposed or refractory to lenalidomide (LEN), a proteasome inhibitor (PI) and an anti-CD38 agent (triple class exposed). Methods: Eligibility criteria included > 1 prior lines of treatment (LoT), LEN and PI exposure and refractoriness to the last LoT. POM was administered at 4 mg days 21/28 days, DEX 40 mg (20 mg age > 75 years) weekly in conjunction with IV belamaf administered as a SINGLE dose of 1.92 mg/kg Q4W or 2.5 mg/kg Q4W, Q8W or Q12W, or SPLIT equally (2.5 or 3.4 mg/kg) on days 1 and 8 Q4W. Responses were assessed by International Myeloma Working Group (IMWG) criteria and adverse events (AEs) were graded by CTCAE criteria except for corneal findings which were also graded by the pre-specified keratopathy and visual acuity (KVA) scale. In Part 1 up to 12 pts were enrolled in each cohort to inform the recommended part 2 dose (RP2D). In part 2, 23 patients will be enrolled to provide 35 patients (inclusive of the 12 treated at the RP2D of 2.5 mg/kg Q8W in Part 1) for overall response determination. Results: At data cut-off (April 11, 2022), 54 triple class exposed pts had been enrolled in the following dose levels and schedules: 1.92 mg/kg Q4W (n=6), 2.5 mg/kg (SINGLE and SPLIT) Q4W (n=6), 2.5 mg/kg Q8W (n=26), 2.5 mg/kg Q12W (n=12), and 3.4 mg/kg SPLIT (n=4). The median age was 67.5 years (range 36-85) and median prior LoT was 3 (range 2-5). Prior therapies (exposed/refractory) included stem cell transplant (61.1%), PI (100%/79.6%), LEN (100%/92.6%), anti-CD38 (100%/100%) and 72.2% triple class refractory. The most frequent grade 1-2 AEs reported in all cohorts were keratopathy (an ophthalmologic finding) (68.6%), decreased best-corrected visual acuity (BCVA) (60.8%), fatigue (51.0%), thrombocytopenia (35.3%), and blurred vision (33.3%). Grade 3/4 AEs reported in >20% of pts across all cohorts, were keratopathy (54.9%), neutropenia (37.3%), thrombocytopenia (27.5%), and decreased BCVA (23.5%). Three patients discontinued treatment due to AEs (one G4 decreased visual acuity, one G3 elevated ALT, and one due to myelodysplastic syndrome) and three grade 5 AEs were observed (one from myeloma progression, one from lung infection, and one from myelodysplastic syndrome). At data cut-off, 50/54 patients were evaluable for response. Across all cohorts the ORR was 86.0% (60.0% > VGPR). Responses by dosing cohort are summarized in Table 1. At a median follow-up of 5.7 months, the median PFS (n=49 at a data-cut of March 28, 2022) was 15.6 months (95% CI: 12.9, NYR; across all cohorts). Conclusions: Patients who are triple class exposed/refractory remain challenging to treat and require therapies with novel mechanisms of action. In the recent LocoMMotion study, triple class exposed MM patients who prospectively received real-life standard of care (SOC) therapies demonstrated an overall response rate (ORR) of 29.8% and median PFS of 4.6 months. Thus, the combination of Bela-Pd represents an improvement over widely available SOC treatments for this poor prognosis patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma, a Real-World Single Center Experience

Introduction Belantamab mafodotin is an antibody drug conjugate targeting B-cell maturation antigen (BCMA) with single agent activity around 32% in the DREAMM2 phase II trial (Lonial et al, Cancer 2021). Side effects, including keratopathy and reduced best corrected visual acuity (BCVA), often necessitate dose reduction and dose delays which may limit efficacy. The aim of this study was to assess response rates, dose modifications, and frequency of ocular adverse events in patients treated with belantamab mafodotin in a real-world setting and in relation to prior treatment with BCMA targeted therapies. Methods All patients treated with at least one dose of commercial belantamab mafodotin at Memorial Sloan Kettering Cancer Center between October 1, 2020 and July 11, 2022 were included in the study. Descriptive statistics were used to assess patient characteristics, response rates, and rate of adverse events. Kaplan Meier curves were used to assess progression free survival (PFS) and overall survival (OS). Results Eighty-two relapsed/refractory multiple myeloma patients were included; 40 (49%) were women median age was 68 years, and 50 patients (61%) had high risk cytogenetics. Twelve patients were treated on the Expanded Access Program with belantamab mafodotin prior to receiving commercial drug. Patients had a median of 6 (range 2-14) prior lines of therapy, all had received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. Sixteen patients (20%) had received one or more BCMA-targeted agents including a bi-specific antibody (N=5), chimeric antigen receptor (CAR) T cell (N=12), and trial therapy with belantamab mafodotin (N=1). Patients received a median of 4 cycles (range 1-31) of belantamab mafodotin. The majority, 96% (N=79), as single agent, while 3 patients were received belantamab mafodotin in combination with other anti-myeloma agents. The overall response rate (ORR) in all patients was 45%; 37/82 patients. Of these, 10 achieved a partial response (PR); 14 patients achieved a very good partial response (VGPR), and 13 patients achieved a complete response (CR) (Table). The median duration of response for patients in the ORR cohort was 11 months. Eighteen patients had stable disease (SD) and 27 patients had progressive disease (PD). The median PFS was 6 months and median OS was not reached. At the end of follow up, 19 patients continued belantamab mafodotin therapy and 28 patients had died. In a separate analysis of patients not included in the Expanded Access Program, the ORR was 43%; 8 had a PR, 13 had a VGPR, and 8 patients had a CR. Of the 16 patients who had prior exposure to BCMA targeted therapy, 5 patients had a PR or better (3 VGPR, 2 CR), 2 patients were in a VGPR/CR at start and continued to respond, 3 patients had SD while 6 patients had PD. The median PFS was similar in patients that were BCMA exposed and those that were BCMA naïve (Figure). Fifty-six patients (68%) had any grade of ocular toxicity per the Keratopathy and Visual Acuity (KVA) scale; 26 patients had grade 1, 15 grade 2, 12 grade 3, and 2 patients had grade 4 keratopathy, respectively. Twenty-six patients had presence of corneal microcysts (information missing in 11 patients). Forty-five patients experienced a decline in BCVA; 22 patients had grade 1, 13 had grade 2, 3 had grade 3, and 1 patient had grade 4 decline in BCVA, respectively (grade missing in 4 patients). The dose of belantamab mafodotin was reduced from 2.5 mg/kg to 1.92 mg/kg in 36 patients while 29 patients had dose delays, the majority due to ocular adverse events but also due to baseline cytopenia, infection, and patient preference. Most patients who had dose modifications due to ocular events were able to continue therapy on a lower dose with maintained response. Nine patients discontinued treatment due to keratopathy, 3 of whom had ongoing grade 1 keratopathy at the end of follow up. Conclusion In this heavily pre-treated multiple myeloma patient population, the ORR was 43-45% which is similar or better than the DREAMM2 phase II trial. The rate of ocular toxicity (68% keratopathy) was comparable to previous reports. Importantly, 5 of 16 patients with exposure to prior BCMA exposure achieved a PR or better while 5 had SD. The PFS was similar in BCMA exposed and BCMA naïve patients. These are encouraging outcomes for belantamab mafodotin in the real-world setting with responses and toxicities comparable to those reported in clinical trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ocular Adverse Events in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in a Phase 1/2 Trial

Introduction Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. In pts refractory to immunomodulatory drugs, proteasome inhibitors, and antiCD38, belamaf plus pomalidomide and dexamethasone induced a very good partial response (VGPR) or better rate of 69.2% and a median progression-free survival of 16.2 months (Trudel S, ASH 2021). Corneal examination findings (e.g., keratopathy) and visual acuity changes are common with belamaf, warranting belamaf dose modifications (dose reduction, dose holds) or treatment discontinuation. Here, we evaluate the ocular adverse effects of belamaf and their impact on daily functioning in pts participating in the phase 1/2 BelaRd study. Methods The ongoing, prospective, open-label, 2-part, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 adult pts with TI NDMM. In Part 1 of the study (dose selection), 18 pts are randomized (1:1:1) in 3 cohorts to receive belamaf 2.5, 1.9, or 1.4 mg/kg doses by intravenous infusion once every 8 weeks (Q8W) plus Rd and the safety/tolerability of the combination is evaluated for pts with ≥4 weeks of follow up. As a safety review found no unexpected findings, an additional 6 pts were enrolled in each dose cohort to select the belamaf recommended phase 2 dose (RP2D). Part 2 (dose expansion; not initiated) will further evaluate the safety and clinical activity of belamaf RP2D plus Rd. Ocular assessments include best corrected visual acuity (BCVA), using Snellen chart and manifest refraction, and corneal exam using slit lamp microscopy. Ocular symptoms are classified by Common Terminology Criteria for Adverse Events and dry eye disease severity and vision-related functioning is assessed with the patient-reported Ocular Surface Disease Index (OSDI). In Part 1 of the study, severity of corneal events is assessed with the Keratopathy Visual Acuity scale. This descriptive analysis included all Part 1 pts from the BelaRd study (data cut-off: 24 June 2022). Results Thirty-six pts were included in this analysis, who were followed up for a median of 9.5 months (range 3.2-15.4). At baseline (cycle 1 day 1), all pts had ocular comorbidities. During follow-up, most of OSDI assessments indicated that there was an impact of study treatment on activities of daily living (ADLs) 'some' or 'none of the time', while only <2.0% of OSDI assessments indicated the impact was 'all' or 'most of the time' (Table). The most common any grade (gr) ocular adverse events (OAEs) across cohorts were dry eye and visual acuity reduced. Gr 3 OAEs were observed only for visual acuity reduced, visual impairment, and cataract; no Gr 4 OAEs were observed. Belamaf doses skipped due to OAEs per the total number of planned belamaf administrations were 23/68 (33.8%), 15/73 (20.5%), and 10/69 (14.5%) in cohorts 2.5, 1.9, and 1.4 mg/kg, respectively. For the entire pt population, median times to resolution of keratopathy and BCVA change from baseline were 2.1 months (range 0.7-11.1) and 2.0 months (range 0.3-6.9), respectively; across cohorts, numerically similar median times to resolution were observed for each OAE Conclusions No new ocular safety signals were observed with belamaf plus Rd in the upfront treatment of TI pts with NDMM; the observed OAEs were within the anticipated range with the use of belamaf. Keratopathy and BCVA change from baseline were resolved by a median of ~2 months; for each of these OAEs, similar times to resolution were recorded, across dose cohorts. Belamaf plus Rd had a minor impact on ADLs, with the patients receiving 1.4 and 1.9 mg/kg doses being the least impacted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Visual function and disability are associated with microcystic macular edema, macular and peripapillary vessel density in patients with neuromyelitis optica spectrum disorder.

To assess macular and peripapillary vessel density and neurodegeneration in eyes with and without microcystic macular edema (MME) in neuromyelitis optica spectrum disorder (NMOSD) patients while investigating their association with visual impairment and disease disability. This is a cross-sectional study. A total of 52 eyes from 29 NMOSD patients were recruited, including 8 eyes with MME from 7 patients. Optical coherence tomography angiography (OCTA) images were analyzed to quantify the radial papillary capillary density (RPCD), and the density of macular microvascular network in both the superficial retinal capillary plexus (SRCP) and the deep retinal capillary plexus (DRCP). Thicknesses of the neural retinal layers centered on the fovea and the optic nerve head were also collected by OCT. Best-corrected visual acuity (BCVA) and Expanded Disability Status Scale (EDSS) scores were assessed for all patients. Microvascular densities and retinal sublayer thicknesses were compared among groups, and correlations of these vascular and structural parameters with BCVA and EDSS scores were determined. Patients with NMOSD and MME had significantly decreased visual acuity and worse EDSS score than patients without MME (P = 0.01 and 0.002, respectively). The vessel density in SRCP and RPCD were significantly lower in eyes with MME and ON compared to that of eyes with ON but without MME and eyes without MME or ON. Impairment of visual acuity and disease severity were significantly negatively associated with the reduction of SRCP vessel density and RPCD but were not related to DRCP vessel density. MME were correlated with worse visual impairment and disability in NMOSD patients. Sparse SRCP vessel density and RPCD were observed in NMOSD MME eyes and correlated with worse BCVA and EDSS scores.

Impact of gender on outcomes following single-level anterior lumbar interbody fusion

BackgroundThere have been a multitude of studies attempting to identify the relationship between gender and postoperative outcomes; however, few studies have examined how this relationship may affect outcomes after anterior lumbar interbody fusion (ALIF) surgery. We aim to better characterize the impact that self-reported gender may have on patient reported outcome measures (PROMs) and achievement rates of minimum clinically important difference (MCID) after ALIF. MethodsA retrospective database of a single spine surgeon was searched for patients who had undergone single-level ALIF. Indications for surgery including acute trauma, infection, or malignancy were excluded. The population was separated into cohorts by self-reported gender, female or male. PROMs were recorded and compared within groups to their preoperative baselines and between groups. MCID achievement rate was compared between groups. Results140 patients were identified for this study, with 68 patients self-identifying as female gender. The male gender cohort was found to have a significantly greater prevalence of hypertension (p = 0.018). Both cohorts showed significant improvement during at least one or more postoperative time points for each evaluated outcome measure (p ≤ 0.048, all). No significant difference in mean PROM scores was noted between cohorts at any time point for any measured outcome. The female gender cohort had significantly greater MCID achievement rates for visual acuity scale (VAS) back pain overall and at the 6-month time point (p ≤ 0.043, both). The female gender cohort also had significantly greater achievement of MCID at the 1-year time point for VAS leg pain (p = 0.017). ConclusionBoth female and male gender cohorts demonstrated significant improvement in all outcomes measured at one or more postoperative time points. Postoperative outcomes did not differ by gender. MCID achievement was more common in female patients. Female patients may experience more tangible clinical improvement after ALIF compared to male patients.

Paper 69: Traumatic Rotator Cuff Tears Have Greater Improvements in Functional Outcomes than Non-Traumatic Tears Following Arthroscopic Rotator Cuff Repair

Objectives:Rotator cuff tears may occur due to a traumatic event that causes acute tearing of the rotator cuff tendons or secondary to chronic tendon degeneration and subsequent atraumatic tearing. The role that tear etiology plays in outcomes after repair is not well understood. The purpose of this study is to determine if a difference exists in outcomes after rotator cuff repair based on tear etiology.Methods:221 consecutive patients who underwent arthroscopic rotator cuff repair were evaluated with prospectively collected preoperative and at least 2-year postoperative data via chart review. Shoulder range-of-motion, strength and standard shoulder physical exam findings were recorded both preoperatively and postoperatively. Outcome measures including visual acuity scale pain score (VAS), subjective shoulder value (SSV), Patient-Reported Outcomes Measurement Information System (PROMIS) scores (both mental and physical components), and American Shoulder and Elbow Surgeons Scores (ASES) were examined.Results:Of the 221 patients, 73 had traumatic tears and 148 had atraumatic/degenerative tears. There were no differences in age, body-mass-index, or Charlson comorbidity index between groups. Patients in the atraumatic cohort had significantly longer duration of symptoms prior to presentation (17.9 months vs 6.5 months, p<0.05). Preoperatively, the traumatic cohort had less motion to forward elevation (138.0° vs 151.7°, p<0.05). Postoperatively, both groups experienced significant improvements in VAS and SSV scores (p<0.05). However, only the traumatic cohort demonstrated improvements in ASES and the physical PROMIS scores. Patients with traumatic rotator cuff tears had greater improvements in SSV (40.6% vs 29.2%, p<0.05), forward elevation (21.6° vs 2.3°, p<0.05), and strength to forward elevation, external rotation, and internal rotation compared to those with atraumatic tears (p<0.05).Conclusions:Patients with traumatic rotator cuff tears experience greater improvements in range-of-motion, strength, and perceived shoulder function than those with degenerative/atraumatic tears.

Exploring alternative dosing regimens of single-agent belantamab mafodotin on safety and efficacy in patients with relapsed or refractory multiple myeloma: DREAMM-14.

TPS8073 Background: Belantamab mafodotin (belamaf: BLENREP) is a first-in-class, monomethyl auristatin F (MMAF)-containing, B-cell maturation antigen (BCMA)-directed antibody–drug conjugate (ADC). In the DREAMM-2 study, belamaf showed deep responses with a manageable safety profile in patients with relapsed/refractory multiple myeloma (RRMM). At 13 months of follow-up, the median duration of response was 11 months and overall survival was 13.7 months at the 2.5 mg/kg Q3W dose. Corneal events are common and expected with belamaf and other MMAF-containing ADCs. In DREAMM-2, corneal events were managed with dose modifications. Clinical responses were observed even with prolonged dose holds, suggesting alternative dosing regimens may lower corneal event rates without compromising efficacy. The DREAMM-14 study (NCT05064358) will investigate if an improved benefit/risk profile of single-agent belamaf can be achieved by modifying the dose, schedule, or both, relative to the approved dosing regimen (2.5 mg/kg Q3W). Methods: This Phase II, randomized, open-label study will include adults with RRMM who had ≥3 prior lines of therapy (LOT), including an anti-CD38 monoclonal antibody, an immunomodulatory agent, and a proteasome inhibitor. Patients with corneal epithelial disease (except nonconfluent superficial punctate keratitis) or with prior exposure to BCMA-targeted therapies, or ADCs will be excluded. Patients will be randomized into Arms A–D (n=40 each) and Arm E (n=20) in parallel and stratified by the International Staging System (I vs II vs III) and prior LOT (3 vs ≥4). Belamaf will be administered as follows—Arm A: 2.5 mg/kg Q3W; Arm B: 1.9 mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E: 1.9 mg/kg Q6W with ocular event-related dose modifications based on oncology staff assessment of ocular symptoms (patient-reported symptoms using the Ocular Surface Disease Index), and visual acuity (Snellen chart or equivalent) in addition to corneal findings assessed by an eye care specialist. Patients in all Arms will have response assessments, safety assessments, and ophthalmic exams performed by an eye care specialist Q3W regardless of dosing schedule. Ocular event-related dose modifications (except in Arm E) will be guided by a modified Keratopathy and Visual Acuity scale. The primary endpoint will be incidence of ocular events. Key secondary endpoints include ocular safety and tolerability, overall safety and tolerability, pharmacokinetics, and efficacy outcomes. Follow-up for progression-free survival will be Q3W until progressive disease, start of new anticancer therapy, withdrawal of consent, end of study, or death. Status: Recruitment is ongoing. Funding: GSK (Study 209628); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT05064358.