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LINKED CONTENTThis article is linked to Quinn et al papers. To view these articles, visit https://doi.org/10.1111/apt.16859 and https://doi.org/10.1111/apt.16954

e24125 Background: Gynecologic, gastrointestinal (GI), and thoracic cancers account for significant morbidity and mortality in the U.S. Women with these types of cancers frequently experience psychological distress, among other poor outcomes. Previous research has indicated that mindfulness-based interventions, such as yoga, can be effective in decreasing distress in cancer patients. Notably, this research has primarily been conducted in a breast cancer population with limited research assessing the feasibility, acceptability, and/or efficacy of this type of intervention in other prevalent and impactful cancers among women. The purpose of the present study was to assess the Feasibility and Acceptability of a yoga intervention for women with gynecologic, GI, or thoracic cancers. Methods: A total of 124 women diagnosed with a gynecologic, GI, or thoracic cancer in the prior year were recruited via outpatient oncology clinics to participate in a 10-week, group-based manualized yoga intervention entitled “Stilling the Waters of Uncertainty” (Author: E. Kacel) that is nearing the end of accrual. Participants completed an Acceptability evaluation following each yoga session with ratings on a 5-point Likert scale from “not at all” to “extremely.” Feasibility of the study was operationalized as percentage of eligible participants who (a) enrolled, (b) attended sessions, and (c) completed post-intervention assessment. Acceptability was operationalized as the percentage of participants with average session ratings of “very” or “extremely” for intervention usefulness, enjoyableness, safety, clarity, relevance, and likelihood of continuing to practice skills. Criteria for operationalizing Feasibility and Acceptability for this study were defined a priori based on recommendations of Bowen and colleagues (2009). A minimum of 80% for each measure of feasibility and acceptability was set as the a priori threshold of success in each domain. Results: All measures of Feasibility were below the a priori benchmark of 80%: Of the 318 eligible patients approached for participation, (a) 124 patients (39.0%) enrolled; 49/124 (39.5%) attended at least 1 yoga session; 44/124 (35.4%) attended at least 8 sessions; and (c) 41/124 (33.1%) completed post-intervention assessment procedures. At least 80% of attendees rated the intervention as “very” or “extremely” useful, enjoyable, safe, and clear; 75.5% and 79.6% of attendees rated the intervention as “very” or “extremely” relevant and likely to be continued to be practiced. Conclusions: The results of this study indicate that a yoga intervention for women with prevalent non-breast cancer types did not meet a priori criteria for feasibility. However, participants who attended at least 1 session rated the intervention as generally acceptable. Future research is needed to improve study/intervention feasibility in this population. Clinical trial information: NCT03385577.

12129 Background: Depression, anxiety, and fear of cancer recurrence (FCR) constitute prevalent psychological concerns necessitating further attention in developing supportive care interventions for women with gynecologic, gastrointestinal, and thoracic cancers. Recent evidence indicates that such concerns may be especially severe among underserved women of color and women affected by low-socioeconomic status (SES). The purpose of the present study is to evaluate the magnitude of changes in depression, anxiety, and FCR associated with a mindfulness-based yoga intervention among a diverse sample of women with these cancers. A second aim is to identify how changes in these concerns may differ across sociodemographic groups. Methods: Women with gynecologic ( n=86), gastrointestinal ( n=17), or thoracic ( n=20) cancers were enrolled in a group-based 10-week yoga intervention utilizing mindfulness meditation, relaxation, and gentle yoga. Prior to and following intervention, participants were administered assessments, including the Beck Depression Inventory – Second Edition (BDI-II) to measure depression, the State-Trait Anxiety Inventory (STAI) to assess anxiety, and the Fear of Cancer Recurrence Inventory (FCRI) to evaluate aspects of FCR. Mixed-linear models evaluated change in outcomes from pre- to post-intervention, with conditional models assessing the effects of age, race/ethnicity, and SES on change. Analyses were conducted prior to trial completion due to approaching accrual period termination. Results: The sample demonstrated a mean age of 58.46 ( SD=10.82) and mean SES score of 3.98 ( SD=1.55) using a 1 to 7 composite scale. Twenty-six percent of participants were of racial and/or ethnic minority status ( n=32). Significant declines in total depressive symptoms, somatic depressive symptoms, state anxiety, and psychological distress due to FCR were observed across the sample. Higher SES was associated with significantly greater reductions in total depressive symptoms and affective depressive symptoms, specifically. Women of color experienced significantly greater declines in somatic symptoms compared to non-Hispanic White women. Conclusions: This mindfulness-based yoga intervention was associated with significant reductions in depressive symptoms, state anxiety, and psychological distress related to FCR among women with gynecologic, gastrointestinal, and thoracic cancers. Higher SES and underserved race/ethnicity status moderated some of these effects. Future research should explore the efficacy of this intervention among diverse women in a randomized clinical trial context. Clinical trial information: NCT03385577.

8038 Background: Multiple myeloma (MM) predominantly affects older patients (pts) (median age at diagnosis 69 yrs) in whom comorbidities must be considered to manage the disease appropriately. Some anti-MM therapies can be associated with ocular toxicities and require careful attention when used among pts with pre-existing ocular comorbidities (OC). In 2018, 41% of Medicare enrollees had OC. Despite the potential implication on treatment decisions, information on pre-existing OC (e.g., disorders of lens, glaucoma) in MM pts is limited. This study aims to describe the prevalence of OCs among real-world pts with MM in 2011-2020 in the US. Methods: Adults with newly diagnosed MM (NDMM) with or without treatment, with 1L systemic therapy, and with relapsed/refractory MM (RRMM) who received up to 4 lines of systemic therapies (LOT) for MM were identified in the IQVIA PharMetrics Plus data. The index date was the date of initial MM diagnosis or a LOT initiation date. The prevalence of OC in each group was defined as the presence of any OC ICD 9/10 diagnosis codes in the 12 months prior to the index date. OCs (e.g., disorders of conjunctiva, lens, choroid, retina, glaucoma) were considered a potentially MM-related disease manifestation or MM treatment-related toxicity based on published literature and clinical expert opinion. Results: The median age at initial MM diagnosis was 64 yrs overall (N=49,814), and 63 yrs among treated pts (N=22,963). The median age was 63 yrs at 1L initiation and 64 yrs at 2L, 3L, and 4L initiation. The prevalence of OC at initial MM diagnosis was 39.0% overall and 35.2% among treated pts (Table). The OC prevalence was 35.8% prior to 1L initiation and higher in RRMM pts (42.1%, 44.9%, and 45.7% prior to 2L, 3L, and 4L initiation, respectively). This trend was observed across all OC categories, among MM-related OCs, and across all age groups. The prevalence of OC by MM stage was stable over the years. Conclusions: Approximately 40% of NDMM pts have a pre-existing OC, and the prevalence increases with the number of LOT in RRMM. While some OC may be due to aging, the impact of OC on treatment decisions for MM should be explored. [Table: see text]

4079 Background: HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs) and are associated with poor overall survival (OS) in patients with metastatic disease. HER2 overexpression is associated with an increased risk of disease recurrence in patients with resected BTC. There is limited data on targeting HER2 in BTC harboring activating somatic HER2 mutations. Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has demonstrated activity in several HER2-mutant solid tumors. Methods: SUMMIT is an open-label, single-arm, multi-cohort, phase 2, ‘basket’ trial of neratinib in patients with solid tumors harboring oncogenic HER2 somatic mutations. The primary objective of the BTC cohort was to estimate objective response rate (ORR). Secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), OS, response duration, safety, and tolerability. Retrospective central confirmation of locally reported HER2 mutation (next-generation sequencing on archival or fresh tumor tissue using MSK-IMPACT or in cfDNA extracted from plasma by MSK-ACCESS) and association with outcome was an exploratory endpoint. This trial is registered with ClinicalTrials.gov (NCT01953926). Results: 25 treatment-refractory patients with metastatic BTC were enrolled (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers). ORR was 16% (95% CI 4.5–36.1%) and CBR was 28% (95% CI 12.1–49.4%). Median PFS and OS were 2.8 (95% CI 1.1–3.7) and 5.4 (95% CI 3.7–11.7) months, respectively. Median PFS for the gallbladder, cholangiocarcinoma and ampulla cohorts was 3.7 (95% CI 0.8–6.4), 1.4 (95% CI 0.5–9.1), and 1.1 (95% CI 1.1–3.8) months, respectively. Corresponding median OS values in these cohorts were 9.8 (95% CI 2.4–NE), 5.4 (95% CI 0.8–16.2), and 5.0 (95% CI 3.7–10.2) months, respectively. Central mutation confirmation was feasible for 23 of 25 patients; 22 were concordant with enrolment assays. The most common HER2 mutations were S310F (n = 11; 48%) and V777L (n = 4; 17%). Exploratory analyses suggested worse outcomes for HER2-mutant tumors with co-occurring oncogenic TP53 and CDKN2A alterations. Loss of amplified HER2 S310F and acquisition of multiple previously undetected oncogenic co-mutations were identified at progression in one of four responders. Diarrhea (56% any grade) was the most common toxicity. Conclusions: Neratinib is tolerable with modest antitumor activity in patients with BTC harboring HER2 mutations. Although the primary endpoint was met, future studies should evaluate rational combinations to augment and/or prolong responses. Clinical trial information: NCT01953926.

Abstract Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

Summary: The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.

SummaryBackgroundTradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV).AimTo evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics.MethodsWe conducted a randomised, double‐blind, placebo‐controlled, single‐centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2.ResultsThe two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV.ConclusionTradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis.Clinic trials registryClinicalTrials.gov #NCT04849559.

Abstract HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has activity in HER2-mutant tumours. SUMMIT is an open-label, single-arm, multi-cohort, phase 2, ‘basket’ trial of neratinib in patients with solid tumours harbouring oncogenic HER2 somatic mutations (NCT01953926). The primary objective of the BTC cohort was objective response rate (ORR). Among 25 treatment-refractory patients (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers), the ORR was 16%. The most common HER2 mutations were S310F (n = 11; 48%) and V777L (n = 4; 17%). Outcomes appeared worse for ampullary tumours or those with co-occurring oncogenic TP53 and CDKN2A alterations. Loss of amplified HER2 S310F and acquisition of multiple previously undetected oncogenic co-mutations were identified at progression in one responder. Neratinib demonstrated anti-tumour activity in patients with refractory BTC harbouring HER2 mutations. Future studies of rational combinations are warranted.

LINKED CONTENTThis article is linked to Quinn et al papers. To view these articles, visit https://doi.org/10.1111/apt.16859 and https://doi.org/10.1111/apt.16916