Citations

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

4591 Background: EV-302 and CheckMate 901 demonstrated significant survival benefit with enfortumab vedotin-pembrolizumab (EVPembro) and gemcitabine-cisplatin-nivolumab (GemCisNivo) as 1L therapy, respectively, in patients (pts) with la/mUC. However, whether these treatments are cost-effective or not remains unclear. Methods: A three-state Markov model (progression-free, progression and death) was developed. State utilities were derived from published literature. State transition probabilities were informed from point-probabilities and hazard ratios for OS and PFS obtained from the latest follow-up of eligible trials. Average sales price (2024 USD) for individual treatments (excluding ancillary charges) were obtained from the center of medicare and medicaid services (US payer’s perspective). Treatment strategies were modeled in accordance with the dose/schedule reported in the eligible trials. Pts who received GemCis or Gem-carboplatin (GemCarbo) and did not progress were modeled to receive Avelumab maintenance. Half-cycle corrected costs and utilities were accrued over a 10-year lifetime horizon and were discounted at 3%. Monte Carlo simulation was used to estimate quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold (WTP) of 100,000$ per QALY was used. Results: In cisplatin-eligible pts, GemCisNivo demonstrated a 0.8 QALY gain over GemCis at an ICER of 21,127 ($/QALY). GemCisNivo was also associated with an incremental net monetary benefit (INMB) of 63,099$ relative to GemCis. EVPembro demonstrated a 2.4 QALY gain over GemCis at an ICER of 915,283 and a 1.6 QALY gain over GemCisNivo at an ICER of 1,406,308. In cisplatin-ineligible pts, EVPembro demonstrated a 2.4 QALY gain over Gem-carboplatin (GemCarbo) at an ICER of 934,761. Price threshold analyses demonstrated that EVPembro is likely to be cost-effective at a cost of 12,344$ for cisplatin-eligible and 13,374$ per cycle for cisplatin-ineligible pts (original cost: 35,665.60$ per cycle). Sensitivity analysis using a total of 12 cycles for EVPembro showed cost-effectiveness at an ICER of 69,594 relative to GemCisNivo in cisplatin-eligible pts, and at an ICER of 53,099 relative to GemCarbo in cisplatin-ineligible pts. Conclusions: In terms of US payer’s perspective, GemCisNivo is most likely to be cost-effective in cisplatin-eligible pts at the WTP of 100,000 $/QALY. Limiting the number of cycles for EVPembro may render it as a cost-effective 1L treatment in la/mUC pts regardless of cisplatin-eligibility status.

Abstract Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell–associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen–targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.

Goals: To determine long-term efficacy and safety of tCS for treatment of EoE. Background: Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed. Study: This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS. Results: Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence; P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy). Conclusions: Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE.

ABSTRACTBackgroundIntraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear.MethodsIn this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13‐year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics.ResultsOf 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN‐associated cancer and 5 cases of worrisome features) over an average follow‐up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p > 0.05). Combined kidney and liver transplantation (p = 0.005) and pretransplant cholangiocarcinoma (p = 0.012) were associated with IPMN progression.ConclusionIPMN progression is rare after liver transplantation even over an extended follow‐up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

Background Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives. Objective To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I–III. Methods This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I–III between January 2010 and December 2023 were included. Results The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03). Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group. Conclusion Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

BACKGROUND: Sugammadex, aprepitant, and fosaprepitant are increasingly used perioperatively. These medications may interfere with the effectiveness of hormonal contraception. This study assessed anesthesia providers’ use of sugammadex and aprepitant, their knowledge of interactions with hormonal birth control, and patient counseling practices to identify possible knowledge gaps or opportunities for practice improvement. METHODS: In January 2023, an electronic survey was distributed to all anesthesia providers at Mayo Clinic sites (Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida, and Mayo Clinic Health System hospitals). The survey included 32 questions assessing providers’ use of sugammadex and aprepitant, their knowledge of the medications’ interactions with hormonal contraceptives (HC), their perceptions regarding education of these interactions during training, and their perioperative patient counseling practices. The collected data were analyzed using descriptive statistics. RESULTS: A total of 337 of 1092 (31%) providers completed the survey. While almost all respondents (324; 96%) knew that sugammadex may interfere with oral contraceptive effectiveness, only 158 (47%) knew about aprepitant’s potential contraceptive interference. Only 176 providers (52%) knew the recommended duration for alternative contraceptive methods after use after sugammadex, and 119 providers (35%) knew the recommended duration after aprepitant exposure. Most respondents considered the interference of these perioperative drugs with HCs to be clinically relevant (sugammadex, 217, 64%; aprepitant, 191, 58%). Despite the common belief that the decision between these medications and alternatives should be shared between provider and patient, most providers reported rarely engaging in such shared decision-making (SDM) in practice. Most providers recognized the need for preoperative discussions on sugammadex (280, 83%) and aprepitant (257, 76%), yet 184 providers (73%) never or rarely discussed contraception use before surgery for aprepitant, and 135 (36%) never or rarely did so for sugammadex. Lastly, many providers believed that the interference between sugammadex, aprepitant, and HC was poorly taught during training. CONCLUSIONS: The results of this study highlight the need for increased education and awareness among anesthesia providers regarding drug interactions with HCs during the perioperative period. To facilitate SDM, it is imperative that providers discuss alternative medications and the potential need for additional contraception methods after drug administration and communicate the risks with patients preoperatively to enable informed and SDM. The patient’s preferences should be accounted for, especially if they are unwilling or unable to use an alternative contraceptive for 7 to 30 days, thereby avoiding the complexities and burdens of altering birth control methods.