Safety and efficacy of reduced selinexor doses in patients with relapsed/refractory multiple myeloma

A recent study suggests that appropriate dose modifications in selinexor in response to adverse events (AEs) were associated with improved efficacy, reduced AE rates and improved quality of life (QoL) in patients with relapsed/refractory multiple myeloma. The study’s findings were published in the journal, Clinical Lymphoma, Myeloma & Leukemia. 
The BOSTON study, a phase III, open label, randomized, controlled trial included 195 patients with relapsed/refractory multiple myeloma. They were randomized either to once-weekly (QW) 100 mg of selinexor, QW subcutaneous bortezomib (1.3 mg/m2), QW with 20 mg of twice-weekly dexamethasone or to a standard subcutaneous bortezomib and dexamethasone twice-weekly. Primary endpoint was progression-free survival (PFS). Secondary endpoints included Overall response rate (ORR), ≥ very good partial response (VGPR) rate, overall survival (OS), duration of response (DoR), time to next treatment (TTNT), and time to response (TTR) 
Of the total 195 patients enrolled, 126 patients had selinexor dose reductions. The median progression-free survival for patients who received dose reductions was 16.6 months (95% CI 12.9 – NR), while it was 9.2 months (95% CI 6.8, 15.5) for those who did not with a hazard ratio of 0.57 (95% CI 0.36, 0.89). The ORR was 81.7% (95% CI 73.9%, 88.1%) vs 66.7% (95% CI 54.3%, 77.6%) for patients with dose reductions vs in those without dose reductions, respectively. DOR was not reached (95% CI 13.8, NE) in the dose reduction group and was 12.0 months (95% CI 8.3, NE) in the group without reduction (HR = 0.59 [95% CI 0.34, 1.04]). TTNT was 22.6 months (95% CI 14.6, NE) for patients who received selinexor dose reductions, whereas it was 10.5 months (95% CI 6.3, 18.2) for patients who did not receive dose reductions.  
On the EORTC QLQ-C30 Global Health Status/QoL scale, the mean best change from baseline was 10.0 ± 20.5 (95% CI 6.3, 13.7) in the dose reduction group as opposed to 4.0 ± 20.9 (95% CI −1.4, 9.3) in those without dose reduction. After selinexor dose reduction, AE rates that were lower included thrombocytopenia (62.5% before vs. 47.6% after), fatigue (28.1% before vs. 9.9% after), nausea (31.6% before vs. 7.3% after), anemia (17.9% before vs. 10.3% after), diarrhea (12.9% before vs. 5.2% after), and diarrhea (21.5% before vs. 6.4% after).
Based on the above results, it can be concluded that appropriate dose reductions of 100 mg selinexor starting dose may be associated with improved efficacy, reduced AE rates and improved QoL

Nomogram predicts cancer-specific survival for patients with primary gastrointestinal melanoma

According to a recent study, it was validated that nomogram can predict cancer-specific survival and develop a risk stratification system for patients with primary gastrointestinal melanoma. The findings of the study were published in The Turkish Journal of Gastroenterology.
Results from a database of 433 patients with primary gastrointestinal melanoma were included in the study after randomly dividing the participants into training and validation cohorts (8:2). The nomogram was constructed based on the risk factors identified in the multivariate Cox regression analysis. Based on the nomogram, a risk stratification system was developed. Time-dependent receiver operating characteristic, calibration curve, and decision curve analysis were performed.
All cases were randomly divided into either the training (n = 347, 80%) or validation cohort (n = 86, 20%). For all patients, the median cancer-specific survival (CSS) time was 18.0 months (95% CI: 14.7-21.3). The median CSS was 18.0 months (95% CI: 14.5-21.5) and 18.0 months (95% CI: 10.7-25.3) in the training and validation cohorts, respectively (log-rank test, P = .241).
It was found that CSS under the curves of the nomogram for 6-, 12-, and 18-month were 0.789, 0.757, and 0.726 for internal validation, and 0.796, 0.763, and 0.795 for the external validation. Furthermore, the patients were divided into 2 risk sub-groups to study the risk stratification, low-risk (point: 0-182) and high-risk (point: 183-333). The median CSS was 31.0 months (95% CI: 24.5-37.5) in the low-risk subgroup and 8.0 months (95% CI: 6.2-9.8) in the high-risk subgroup. The Kaplan-Meier analysis and the log-rank test demonstrated that the risk stratification was well-differentiated in patients with varying risks of cancer-specific survival.
Thus, it can be concluded that the nomogram prediction model may be practical for validation of cancer-specific survival and development of a risk stratification system in patients with primary gastrointestinal melanoma.
 

Continuous PEGasparaginase dosing regimen decreases hypersensitivity reactions in children with acute lymphoblastic leukemia

A recent study showed that a continuous dosing regimen of PEGasparaginase (PEGasp) can effectively prevent the formation of antibody and reduce the risk of hypersensitivity reactions. These findings were published in the Journal of Clinical Oncology. 
Patients diagnosed with Acute Lymphoblastic Leukemia (ALL) were included in the DCOG ALL11 protocol. These patients were administered PEGasp as part of their treatment. Out of 818 patients, 312 were categorized as medium-risk and were randomized to receive 14 individualized doses of PEGasp. The administration of these doses occurred once every two weeks, following either a non-continuous or continuous schedule after the initial three doses during the induction phase. The primary objective of this study was to assess whether the continuous dosing schedule, without any asparaginase-free interval, would lead to a lower occurrence of hypersensitivity reactions to PEGasp compared to the standard non-continuous dosing schedule. The secondary endpoints of the study included evaluating other asparaginase-related toxicities, asparaginase activity and antibody levels, as well as overall treatment outcome.
In the induction phase, hypersensitivity reactions were detected in 27 out of 818 patients. Following random assignment assignment of 312 medium risk patients, 4 out of 155 (2.6%) patients in the continuous treatment arm and 17 out of 157 (10.8%) patients in the noncontinuous treatment arm reported hypersensitivity reactions. Among these reactions, 2 versus 13 were inactivating reactions. In the continuous treatment arm, the occurrence of inactivating hypersensitivity reactions was 7 times lower. Additionally, antibody levels were notably reduced in the continuous treatment arm. There were no notable differences in the total number of asparaginase-related toxicities between the two treatment groups, besides a lower incidence of elevated amylase in the continuous treatment group. 
As a result, a continuous PEGasp dosing schedule is successful in preventing antibody formation neutralizing and hypersensitivity responses. This continuous schedule demonstrated no rise in toxicity levels and had no impact on the efficacy.
 

The correlation between chronic sinonasal inflammation and nasopharyngeal carcinoma

In a recent systematic review and meta-analysis, the presence of chronic sinonasal inflammation shows a significant correlation with nasopharyngeal carcinoma. Findings of this study were documented in the American Journal of Otolaryngology.

This meta-analysis involved a comprehensive search of four international databases from 1^st January 1973 to 28^th March 2022 for studies addressing sinonasal inflammation and NPC in adults (greater than 18 years old). Case-control, cohort, or cross-sectional studies were included that explored the association between a prior history of sinonasal inflammation and the risk of developing NPC. The incidence of nasopharyngeal carcinoma (NPC) in patients with prior sinonasal inflammation is the outcome.

A total of eight studies, comprising 8,245 individuals diagnosed with NPC and 1,036,087 individuals without NPC, were examined. The overall odds ratio for developing NPC following sinonasal inflammation was found to be 1.81 (95% confidence interval 1.73-1.89). Chronic rhinosinusitis (CRS) exhibited a stronger association with an increased risk of NPC, with an odds ratio of 1.78 (95% confidence interval: 1.68-1.90), in comparison to allergic rhinitis (AR) (odds ratio of 1.60; 95% confidence interval: 1.52-1.68).

Thus, it can be concluded that chronic sinonasal inflammation is strongly linked to nasopharyngeal carcinoma. It is important to thoroughly examine the cause-and-effect relationship and the potential effects of targeted screening using large-scale prospective studies.