Quantification of the living human visual system using MRI methods has been challenging, but several applications demand a reliable and time-efficient data acquisition protocol. In this study, we demonstrate the utility of high spatial resolution diffusion tensor fiber tractography (DTT) in reconstructing and quantifying the human visual pathways. Five healthy males, age range 24–37 years, were studied after approval of the Institutional Review Board (IRB) at The University of Texas Health Science Center at Houston. We acquired diffusion tensor imaging (DTI) data with 1-mm slice thickness on a 3.0 Tesla clinical MRI scanner and analyzed the data using DTT with the fiber assignment by continuous tractography (FACT) algorithm. By utilizing the high spatial resolution DTI protocol with FACT algorithm, we were able to reconstruct and quantify bilateral optic pathways including the optic chiasm, optic tract, optic radiations free of contamination from neighboring white matter tracts.
8060 Background: Belantamab mafodotin (belamaf) is a BCMA antibody drug conjugate approved for the treatment of relapsed refractory multiple myeloma (RRMM) patients (pts) based on the pivotal phase 2 DREAMM-2 study (Lonial et al, Lancet Oncology, 2019), which demonstrated an overall response rate (ORR) of 32%, median progression free survival (PFS) of 2.8 months, and overall survival (OS) of 13.7 months in triple class (proteasome inhibitor, IMiD, and anti-CD38) refractory (TCR) MM. In this single-center retrospective study, we report the efficacy and safety of belamaf in RRMM pts administered in a real-world, standard of care (SOC) setting. Methods: All MM pts who initiated therapy with SOC belamaf, either as monotherapy or in combination, between 11/1/2020 and 11/30/2021 at MD Anderson were included in this study. Response and progression were evaluated using International Myeloma Working Group standard criteria. Keratopathy and best corrected visual acuity (BCVA) adverse events (AEs) were graded per the Keratopathy and Visual Acuity (KVA) scale. The Kaplan-Meier method was used to estimate time to event endpoints. Results: A total of 39 consecutive pts with a median of 7 prior lines of therapy were included in the analysis, of whom 37 pts (95%) received single agent belamaf. Median age was 66 years (range 39-89), 14 of 37 (38%) pts with available FISH had high risk disease (del 17p, t(4;14, and/or t(14;16)), 14 pts (36%) had extramedullary disease, 37 (95%) pts were TCR, 32 (82%) pts were TCR and alkylator-refractory, and 8 pts (21%) were BCMA-refractory. Notably, the majority (69%) of pts in this analysis would have been ineligible for the DREAMM-2 trial based on key eligibility criteria. Median number of belamaf doses administered was 2 (range 1-9). Among 37 pts with measurable, response evaluable baseline disease, the best ORR (≥ PR) was 27% with ≥ VGPR of 3%. The clinical benefit rate (≥ MR) was 35%. Among 8 BCMA-refractory pts, there was 1 PR and 1 MR. Median PFS was 1.8 months and median OS was 9.2 months with a median follow-up of 10.1 months. Median duration of response has not been reached among 10 responding pts. Among 33 pts with a post-treatment ocular exam, 25 pts (76%) developed any grade keratopathy (Grade 1/2/3/4, 9%/55%/12%/0%, respectively) and BCVA changes (Grade 1/2/3/4, 42%/27%/6%/0%, respectively). Median time to first keratopathy or BCVA AE was 1.3 months. The most common reasons for treatment discontinuation were disease progression (75%) and AEs (9%). Conclusions: Our current study in heavily pretreated RRMM pts, of whom the majority would have been ineligible for the DREAMM-2 study, demonstrates an ORR, PFS, and ocular AE profile with SOC belamaf therapy comparable to outcomes reported in the pivotal registration study. Future studies are needed to further define the optimal use and sequencing of belamaf in MM pts, particularly in context of other BCMA-targeting modalities.
Introduction Immune checkpoint inhibitors (ICIs) have improved prognosis in advanced malignancies; however, they may be associated with extensive ocular immune-related adverse events (irAEs) that are sight threatening. Our study aimed to identify the presentation, characteristics, management, and clinical outcomes of ocular irAEs. Methods: In this retrospective, observational case series, we reviewed the medical records of 1280 patients at a large US tertiary cancer center between 2010 and 2020. Results: We identified 130 patients who presented with ocular irAEs (10%) with 69 males (53%) and 61 females (47%). The mean time to toxicity was 6.1 months. Adverse events include corneal toxicity (31%), neuro-ophthalmic (14%), uveitis and scleritis (13%), retinopathy (13%), periocular disorders (11%), and others. IrAEs occurred most frequently with nivolumab (26%). Most ocular irAEs were treated with topical therapy. Advanced cases required systemic corticosteroids and even cessation of ICIs. Conclusion: Our cohort is a large case series highlighting the increased potential of ocular toxicity associated with ICIs. Prompt recognition and management of ocular irAEs can minimize their effect.
Purpose: Targeted cancer therapy (TCT) is a significant advancement in oncology with promising survival improvement in patients with cancer and remarkable effects on various cancers. There is evidence suggesting a connection between specific TCT classes and the occurrence of immune-related adverse events (irAEs). Our study aims to investigate the potential ocular toxicities of different classes of TCT, provide a better understanding of these toxicities, and aid in the future development of screening and management recommendations for ocular irAEs. Design: Retrospective observational case series. Participants: Only ocular immune-related AEs were included in the study; patients on TCT who received a new ophthalmic diagnosis were seen at the MD Anderson Cancer Center. Methods: Between 2010 and 2019, we retrospectively reviewed the medical records of 6,354 patients on TCT at a large US tertiary cancer center. Results: The criteria for data analysis were met by 1861 patients. TCT was associated with a wide range of class-specific ocular irAEs. There was a statistically significant correlation between ocular toxicity with polytherapy with a p-value of <0.001. Furthermore, there was a statistically significant correlation between toxicity and BRAF, epidermal growth factor receptor (EGFR), and ICI <0.001, <0.001, and 0.006, respectively. Conclusion: Our cohort is the most extensive case series in English literature, demonstrating the increased risk of class-specific ocular toxicity associated with TCT, which sheds some light on the importance of developing standardized grading criteria and management guidelines.
While significant strides have been made in the treatment of multiple myeloma, treatment options remain limited and definite, and most patients ultimately succumb to their disease. The urgency for more treatment modalities remains, as patients who are refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies have a median survival of only 5.8 to 13 months. Belantamab mafodotin, a first-in-class antibody-drug conjugate, was approved by the US Food and Drug Administration in 2020 for patients with relapsed or refractory myeloma who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. It produced an overall response rate of 31%, and the median progression-free survival was 2.9 months when administered as a single agent. While generally well tolerated, ocular toxicities were a notable adverse event reported. In this article, we discuss the response data, toxicity profile including ocular toxicities, and treatment management.
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