Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ/γ isoforms currently in clinical development. PI3K-δ/γ inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma. Inhibition of either isoform may also contribute to clinical responses by modulating nonmalignant immune cells. We investigated these dual effects in a TCL cohort from a phase 1, open-label study of duvelisib in patients with relapsed or refractory PTCL (n = 16) and CTCL (n = 19), along with in vitro and in vivo models of TCL. The overall response rates in patients with PTCL and CTCL were 50.0% and 31.6%, respectively ( = .32). There were 3 complete responses, all among patients with PTCL. Activity was seen across a wide spectrum of subtypes. The most frequently observed grade 3 and 4 adverse events were transaminase increases (40% alanine aminotransferase, 17% aspartate aminotransferase), maculopapular rash (17%), and neutropenia (17%). Responders and nonresponders had markedly different changes in serum cytokine profiles induced by duvelisib. In vitro, duvelisib potently killed 3 of 4 TCL lines with constitutive phospho-AKT (pAKT) vs 0 of 7 lines lacking pAKT ( = .024) and exceeded cell killing by the PI3K-δ-specific inhibitor idelalisib. Administration of duvelisib to mice engrafted with a PTCL patient-derived xenograft resulted in a shift among tumor-associated macrophages from the immunosuppressive M2-like phenotype to the inflammatory M1-like phenotype. In summary, duvelisib demonstrated promising clinical activity and an acceptable safety profile in relapsed/refractory TCL, as well as preclinical evidence of both tumor cell-autonomous and immune-mediated effects. This trial was registered at www.clinicaltrials.gov as #NCT01476657.

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Objective Parents and children affected by pediatric cancer are at risk for psychological distress, including depression, anxiety, and post-traumatic stress. A link is believed to exist between parent and child distress; however, no systematic analysis of this relationship has occurred. A meta-analysis was conducted to assess the relationship between parent and child distress among families affected by pediatric cancer. Methods A systematic review and meta-analysis was conducted using EBSCO (searching PsycINFO, MEDLINE, Academic search Premiere, and Health Source: Nursing/Academic Edition) and PubMed. The initial search yielded a total of 29,118 articles. Inclusion criteria were that studies assessed the relation between parent and child distress in the context of pediatric cancer, were written in English, and were published in peer-reviewed journals. 28 articles met inclusion criteria. Results A statistically significant association was found between overall parent and child distress (r = .32, p < .001), such that increased parent-reported distress was associated with increased distress in their children. Significant relationships were also present among each type of parental distress (i.e., depression, anxiety, post-traumatic stress, and global distress; rs = .31–.51, ps < .001) and overall child distress. Moderation analyses via meta-regression indicated that parent proxy-report of child symptoms was associated with a stronger relationship between parent and child distress than child self-report of their own distress. Conclusions Aligned with the social–ecological framework, familial factors appear to be highly relevant in understanding distress following pediatric cancer diagnosis. Indeed, greater parent distress was associated with greater child distress.

This study identified grit as a positive personal asset among AYAs with chronic medical conditions. By introducing a novel construct to the AYA literature, the study expands on the integration of positive psychology and pediatric psychology and underscores the need for greater research on the role of grit in chronic medical condition populations.

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