Citations

ABSTRACT Chimeric antigen receptor T-cell (CART) and T-cell engager (TCE) therapies targeting B-cell maturation antigen (BCMA) are transforming the treatment landscape for relapsed multiple myeloma (MM). However, despite impressive initial response rates, most patients eventually relapse. To investigate this unmet medical need, we applied whole-genome sequencing (WGS) to MM cells from cohorts of 102 relapsed patients treated with anti-BCMA CART and TCE therapies. Several genomic alterations were associated with clinical outcomes, particularly primary refractoriness, including high genomic complexity and mutations in genes regulating plasma cell identity, which predicted resistance to therapy. Single-cell RNA sequencing further revealed that MM cells from refractory patients exhibited high proliferation signatures and reduced expression of TNFRSF17 (encoding BCMA), while were less enriched for plasma cell–associated transcriptional programs, a phenomenon we term “plasma cell identity escape.” This profile was strongly associated with immune dysregulation of CD8 T cells including increased activation and exhaustion. This evolution of MM toward a more proliferative and lineage-divergent state, refractory to the anti-BCMA T-cell redirecting therapies, was functionally validated in preclinical MM mouse models. Collectively, our results comprehensively define the cellular and molecular mechanisms underlying primary resistance to anti-BCMA therapies.

PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Abstract The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient and disease characteristics. In the landmark analysis, rituximab maintenance was associated with improved event-free survival (EFS; median, 49.9 vs 29.7 months; P< .001) as well as overall survival (OS; median, 109.5 vs 74.2 months; P< .001). The EFS and OS benefits were observed across most of the subgroups. EFS and OS differences were statistically significant in those who achieved a complete response to 1L BR (n = 590; median EFS, 62.7 vs 31.1 months [P< .001]; median OS, 136.1 vs 75.3 months [P< .001]), but the analysis among those who achieved a partial response to 1L BR was limited by the small sample size. These results provide additional evidence for the survival benefit of rituximab maintenance after BR in MCL and support its use in clinical trial design and routine practice.

This cohort study evaluates the use of definitive rhinectomy and adjuvant radiotherapy with or without chemotherapy for patients who declined rhinectomy or had unresectable disease.

Abstract Background Topical steroid withdrawal syndrome (TSW) is an adverse event following discontinuation of topical corticosteroids (TCS) and is of growing interest among patients and dermatologists. The absence of well-defined diagnostic criteria and limited insights into the pathomechanisms make diagnosis and future research challenging. Objectives To propose preliminary diagnostic criteria for TSW with the erythemato-oedematous subtype applicable for adult and paediatric populations using a Delphi consensus approach informed by a thorough literature review that summarizes the signs, symptoms and histology of TSW. Methods Eleven clinicians experienced in diagnosing and treating suspected TSW in both children and adults participated in a three-round modified Delphi process. Two rounds of surveys were conducted, with items ranked using a 5-point Likert scale. A predefined consensus threshold of ≥ 75% was established for any one feature to be deemed important. The third round involved a live video conference where the panel reached a consensus on essential diagnostic criteria. Results The panel identified 18 critical diagnostic items, encompassing elements from the patient’s clinical history, signs and symptoms. This includes history of escalating TCS requirement, morphology and distribution differing from primary condition, regional or generalized spontaneous neuropathic pain and severe burning sensation of the skin. Conclusions Differentiating TSW from conditions such as severe atopic dermatitis remains challenging. By emphasizing the common signs and symptoms of TSW, we aim to encourage discussions among healthcare professionals and progress towards the development of a reliable diagnostic tool. An author video to accompany this article is available online.

ABSTRACT A major challenge in hematopoietic progenitor cell apheresis is determining the whole blood (WB) volume to process to achieve a CD34+ cell collection goal. We developed a web‐based calculator app that uses the Collection Efficiency 2 (CE2) model to estimate personalized WB processing volumes needed to reach a prescribed CD34+ cell collection goal. Retrospective evaluation of the app using collection data from two academic medical centers showed that actual processed WB volumes were frequently higher than the app's recommendations. The frequency of potential under‐collection events is predicted to be low had the app‐calculated volumes been utilized. Our findings suggest that using the app's recommendations may lower total WB processing volumes, reducing over‐collection and time spent on the apheresis machine, while maintaining a low under‐collection risk profile.

Abstract Jagim, AR, Dobbs, WC, Horswill, CA, Twohey, E, Fields, JB, and Jones, MT. Prevalence and magnitude weight loss among collegiate wrestlers. J Strength Cond Res 40(1): 90–97, 2026—The purpose of this study was to examine the percentage of wrestlers who compete in their minimal weight class (MWC), and the magnitude of weight loss. Data from the 2023–2024 collegiate season were retrospectively analyzed resulting in a sample of 9,638 collegiate male wrestlers from the National Association of Intercollegiate Athletics ( n = 1,904) and all 3 divisions of the National Collegiate Athletics Association ( n = 7,734). All wrestlers completed skinfold assessments for weight certification at the start of the competition season. The lowest recorded weight class (LRW) achieved by each wrestler during the season was also recorded and used to determine magnitude of weight loss. Out of the 4,605 (53.2%) of wrestlers who competed in their MWC, their average amount of weight loss was significantly higher than those who did not compete in their MWC (3.9 ± 2.5 vs. 3.2 ± 2.9 kg.; p < 0.001), yet they had an initial lower body fat percentage (12.7 ± 2.9 vs. 17.5 ± 4.8%; p < 0.001). At the time of weight certification, wrestlers weighed 8.1 ± 4.5 (95% confidence interval (CI): 8.0–8.2; effect size (ES) = 1.8) kg more than their minimal wrestling weight. The LRW was 3.6 ± 2.9 (95% CI: 3.6–3.7; ES = 1.2) kg lower than their weight at the time of weight certification. Given that slightly more than half of the male wrestlers competed in their MWC, coaches and sports practitioners should recognize that not all athletes follow the traditional assumption of cutting to the lowest possible weight class. Importantly, those who did achieve their MWC had lower initial body fat percentages, limiting the amount of weight they could safely lose. This underscores the need for individualized weight management strategies that consider body composition and health implications.

Abstract Introduction Vasectomy is a highly effective, permanent method of contraception. Vasectomy is commonly performed in the outpatient urology clinic with the patient awake. There is clearly anticipation of pain as well as anxiety associated with the procedure. Objective The objective of our study was to evaluate anticipated versus experienced pain associated with office-based vasectomy. Methods We studied men who underwent vasectomy in May and June of 2022. Men who had no history of scrotal surgery of any kind were asked to score the anticipated pain associated with an office based vasectomy with a score of 0-10. After the vasectomy, patients were asked to rate the pain they perceived with the vasectomy on the same scale (0-10). Results A total of 17 men were asked to rate their pain as discussed in the method section. The median age of men sampled was 38 years of age. All men we treated were given 15 mg of Valium before the procedure and instructed to take the medication 30 minutes prior to their procedure. The average pre vasectomy prediction pain score was 7.5+/- 1.9; the average post-injection perceived pain score was 2.9+/- 1.9. Thus there was an average decrease of over 4 points in the predicted pain versus perceived pain. A two-sample T test was performed; in addition Wilcoxson Signed Rank Test was performed. Both tests showed a statistical significance in the difference between pre and post vasectomy pain scores (p&lt;0.001). Conclusions We found that patients who are undergoing office based vasectomy for the first time have a significantly higher perception of pain versus perception of pain after the injection. We have utilized this data in our clinic to explain to patients that while most patients will predict a high pain score associated with the vasectomy, the vast majority of patients report minimal pain after the procedure. Our study can be particularly helpful in patients who have had significant anxiety about office based vasectomy and for those patients who are deciding between office based vasectomy and vasectomy performed under general anesthesia. Disclosure No