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OBJECTIVE: To identify the optimal dose of selinexor in combination with pomalidomide and dexamethasone (SPd). METHODS: An analysis of efficacy and safety of 2 once-weekly selinexor regimens (60 mg and 40 mg) with pomalidomide and dexamethasone (SPd-60 and SPd-40, respectively) given to patients with relapsed/refractory multiple myeloma (RRMM) in the STOMP (NCT02343042) and XPORT-MM-028 (NCT04414475) trials. RESULTS: Twenty-eight patients (60.7% males, median age 67.5 years) and 20 patients (35.0% males, median age 65.5 years) were analyzed in the SPd-40 and SPd-60 cohorts, respectively. Overall response rate was 50% (95% confidence interval [CI] 30.6-69.4%) and 65% (95% CI 40.8-84.6%), respectively. Very good partial response or better was reported in 28.6% (95% CI 13.2-48.7%) and 30.0% (95% CI 11.9-54.3%) of patients, respectively. Among 27 responders in both cohorts, the 12-month sustained response rate was 83.3% (95% CI 64.7-100.0%) for SPd-40 and 28.1% (95% CI 8.9-88.8%) for SPd-60. Median progression-free survival was 18.4 months (95% CI 6.5 months, not evaluable [NE]) and 9.5 months (95% CI 7.6 months-NE) for SPd-40 and SPd-60, respectively. Twenty-four-month survival rates were 64.2% (95% CI 47.7-86.3%) for SPd-40 and 51.1% (95% CI 29.9-87.5%) for SPd-60. Treatment-emergent adverse events (TEAEs) included neutropenia (all grades: SPd-40 64.3% versus SPd-60 75.0%), anemia (46.4% versus 65.0%), thrombocytopenia (42.9% versus 45.0%), fatigue (46.4% versus 75.0%), nausea (32.1% versus 70.0%) and diarrhea (28.6% versus 35.0%). CONCLUSION: The all-oral combination of SPd exhibited preliminary signs of efficacy and was generally tolerable in patients with RRMM. The overall risk-benefit profile favored the SPd-40 regimen.

PURPOSE: To study the association between tear film hyperosmolarity and ocular light scatter in a cataract surgery population. PATIENTS AND METHODS: Contiguous, 20-second objective scatter index (OSI) scans were recorded in hyperosmolar (≥320 mOsm/L) and normal subjects (

BACKGROUND: Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent head-to-head trial outcomes. OBJECTIVE: To compare the efficacy of OC-01 (varenicline solution) 0.03 mg nasal spray (OC-01 VNS) to lifitegrast 5% ophthalmic solution on tear production and patient-reported eye dryness in patients with dry eye disease (DED) using data from phase 3 clinical trials via MAIC analysis. METHODS: Individual patient data (IPD) from the phase 3 registrational trial of OC-01 VNS and aggregate data from 2 phase 3 trials of lifitegrast in the publicly available XIIDRA New Drug Application were used. Using unanchored MAIC methods, IPD were weighted on clinically relevant baseline variables (age, race, sex, baseline Schirmers test score [STS], and Eye Dryness Score [EDS]) to produce weighted OC-01 VNS datasets matched to the same lifitegrast datasets variables. Least-squares (LS) mean change from baseline (CFB) in STS for OC-01 VNS was calculated using the identical analysis of covariance model and covariates used to calculate the same values for lifitegrast in the XIIDRA New Drug Application and was then compared. LS mean EDS (based on a 100- point Visual Analogue Scale) was compared via analysis of covariance in the weighted OC-01 VNS and lifitegrast datasets. OC-01 VNS at 2 and 4 weeks compared to lifitegrast data at 2 and 6 weeks. RESULTS: Data from 511 subjects (n = 260 treated; 251 vehicle control [VC]) in the OC-01 VNS phase 3 trial, 588 (n = 293 treated, 295 VC) in the lifitegrast phase 3 OPUS-1 trial, and 718 (n = 358 treated, 360 VC) in the lifitegrast phase 3 OPUS-2 trial were analyzed. The LS mean STS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 and OPUS-2 (P < 0.0001 for all comparisons). The LS mean EDS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 (P < 0.0001 for both comparisons) and at 4 weeks vs lifitegrast at 6 weeks in OPUS-2 (P < 0.0001). CONCLUSIONS: This MAIC analysis demonstrates OC-01 VNS produced significantly greater improvement in mean STS and comparable or greater improvement in EDS compared with lifitegrast in phase 3 trials. These findings suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with lifitegrast for the treatment of DED within the conditions of the analysis methodology. DISCLOSURES D White is a consultant for Oyster Point Pharma, Inc. L Hendrix, M Macsai, and A Gibson are employees and shareholders for Oyster Point Pharma, Inc. L Sun was an employee of COEUS, Clinical Research at the time of study conduct and received funding from Oyster Point Pharma, Inc. I Tam is an employee of COEUS, Clinical Research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc was involved in the study design, data collection, data analysis, and preparation of the manuscript and is the manufacturer/licensee of OC-01 (varenicline solution) nasal spray. Oyster Point Pharma, Inc., sponsored the phase 3 OC-01 (varenicline solution) clinical study from which analysis data were obtained.

There is a lack of consensus on therapy sequencing in previously treated multiple myeloma, particularly after anti-B-cell maturation antigen (BCMA) therapy. Earlier reports on selinexor (X) regimens demonstrated considerable efficacy in early treatment, and after anti-BCMA-targeted chimeric antigen receptor-T cell therapy. Here, we present data from 11 heavily pretreated patients who predominantly received BCMA-antibody-drug conjugate therapy. We observe that X-containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survival compared to patients prior anti-BCMA therapies, despite being used later in the treatment course. In an area of evolving unmet need, these data reaffirm the efficacy of X-based regimens following broader anti-BCMA therapy.

BackgroundProteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM).MethodsThe safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib.ResultsThirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months.ConclusionsWeekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.

Background: T-cell–redirecting therapies, such as bispecific antibodies and chimeric antigen receptor T-cells, exploit the cytotoxic capabilities of the immune system to destroy cells expressing specific surface antigens, including malignant cells. These therapies have demonstrated unprecedented rates, depth, and duration of responses in relapsed and refractory multiple myeloma. However, there are significant challenges in implementing these therapies into practice, which require multidisciplinary and multicenter coordination and significant healthcare resources to effectively manage these patients. So far, there are no Canadian guidelines for the effective implementation and use of T-cell–redirecting therapies. Methods: This consensus statement was developed based on three advisory meetings held in March, July, and November 2023. During these meetings, a panel of Canadian subject matter experts and representation from Myeloma Canada gathered to discuss the optimal procedures for the use of T-cell–redirecting therapies in the treatment of multiple myeloma. Members of the panel performed a thorough review of randomized clinical trials, real-world data, and other current literature, and provided their up-to-date clinical experience with T-cell–redirecting therapies in Canadian practice settings. Subsequently, asynchronous working groups were appointed to develop unified criteria for patient selection, appraise referral pathways, and devise strategies for management of short-term and long-term adverse events arising from the use of T-cell–redirecting therapies in multiple myeloma. Results: Here, we present recommendations for optimizing patient selection, referral pathways, and adverse event management in the Canadian practice setting. These recommendations are relevant for hematologists/oncologists, oncology nurses, pharmacists, nurse practitioners, physician assistants, and other providers who treat patients with multiple myeloma, as well as individuals with multiple myeloma and their care partners. These recommendations will be of interest to clinicians who treat patients with MM at community clinics and hospitals and who may be interested in referring patients for T-cell–redirecting therapy. [ABSTRACT FROM AUTHOR]

Background: Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature. Methods: We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022. Results: The median age was 46 years old (range: 25.6–50). Most patients fell into the R‐ISS II category (72.7%), and 24.1% had high‐risk cytogenetics. The majority of patients (89.9%) received a proteasome inhibitor‐based first‐line treatment, 92.1% received a stem cell transplant, and 65.6% had maintenance therapy post–autologous stem cell transplant (ASCT). Median follow‐up from initial treatment to patients' last follow‐up was 48.5 (range: 0–155) months. Median progression‐free survival (PFS) was 45.0 months (95% CI: 40.2–50.0). Maintenance therapy post‐ASCT improved median PFS to 52.3 months (95% CI: 43.1–68.2), compared to 23.6 months (95% CI: 20.0–34.8) without maintenance [p < 0.001]. Conclusion: Although the overall survival has not yet been reached in this young population, our reported median PFS of only 45 months highlights the urgent need to develop innovative treatments to induce more profound and durable responses. [ABSTRACT FROM AUTHOR]

Objective scatter index (OSI) scans were recorded in hyperosmolar (≥ 320 mOsm/L) and normal subjects (< 308 mOsm/L) with cataract nuclear opacity ≥ 3. OSI was measured at screening, baseline and 90 days following surgery. Along with symptoms of ocular surface disease, slit-lamp examination included corneal staining (0– 3), tear film breakup time (TBUT) and evaluation of meibomian gland disease (MGD). An additional cohort of hyperosmolar subjects were measured for OSI at screening, baseline, and 5, 10, 15 and 30 minutes following instillation of 0.18% sodium hyaluronate (HA). Results: Thirty-one eyes of 31 patients were included. There was a significant difference in post-operative OSI variation when comparing hyperosmolar (0.65± 0.30, N=11) to normal subjects (0.33± 0.11, N=10, p=0.005). Of note, there were no significant differences in OSI variation when subjects were sorted by staining (p=0.9), TBUT (p=0.7), symptoms (p=0.7), or MGD status (p=0.9). Instillation of 0.18% HA (N=10) did not alter OSI at 5 minutes, but significant reductions in OSI of 28.8%, 38.5% and 36.7% (all p < 0.001) were observed at 10, 15 and 30 minutes. Conclusion: Hyperosmolar patients exhibited significantly increased variation in light scatter following cataract surgery that was undifferentiated by staining or TBUT. Elevated osmolarity may be indicative of light scatter equivalent to that of a grade 2– 3 cataract. [ABSTRACT FROM AUTHOR]

Introduction: Two phase 3 studies demonstrated superior efficacy of intravenous daratumumab (DARA IV) plus bortezomib/melphalan/prednisone (ALCYONE) or lenalidomide/dexamethasone (Rd; MAIA) versus standard-of-care regimens for transplant-ineligible newly diagnosed multiple myeloma. In these studies, patients could switch from DARA IV to subcutaneous daratumumab (DARA SC) while receiving daratumumab monotherapy in ALCYONE (as of Cycle 11) or daratumumab plus Rd in MAIA. The phase 3 COLUMBA study demonstrated noninferiority of DARA SC to DARA IV. DARA SC reduced administration time, allowing patients to spend less time in healthcare settings, a relevant practical consideration for patient care in the COVID-19 pandemic/settings of limited healthcare resources. Methods: DARA SC 1800 mg was administered every 4 weeks, per approved dosing schedules. We evaluated safety and patient-reported experience (ALCYONE only) among patients who switched from DARA IV to DARA SC. Results: Fifty-seven patients in ALCYONE and 135 in MAIA switched to DARA SC. Three (2.2%; MAIA) patients reported injection-site reactions, all of which were mild. No infusion-related reactions occurred with DARA SC. In ALCYONE, >80% of patients preferred DARA SC over DARA IV. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 5.3% of patients in ALCYONE and 25.9% in MAIA; one (0.7%; MAIA) patient experienced a TEAE with an outcome of death. Conclusion: For transplant-ineligible newly diagnosed multiple myeloma, DARA SC (monotherapy/with Rd) was safe and preferred over DARA IV. ClinicalTrials.gov, NCT02195479/NCT02252172. [ABSTRACT FROM AUTHOR]