Real-world experience of pegcetacoplan in paroxysmal nocturnal hemoglobinuria.

Pegcetacoplan significantly improves outcomes for patients with paroxysmal nocturnal hemoglobinuria (PNH) experiencing extravascular hemolysis (EVH) on eculizumab, leading to approval in 2021/2022 (USA/Europe). We report the first collaborative real-world evidence on pegcetacoplan use in UK and France. A total of 48 patients were either currently receiving or previously received pegcetacoplan (2019-2023). A total of 12 patients had participated in the PEGASUS clinical trial, continuing treatment after trial completion. Five patients were on combination treatment of C5 inhibition and pegcetacoplan. Mean pegcetacoplan duration was 20.2 months. Indication for pegcetacoplan was EVH on C5 inhibitors (Eculizumab, n = 29, Ravulizumab n = 16, others n = 3) with 35/48 patients requiring blood transfusion within the previous 12 months. Mean hemoglobin and reticulocyte count at pegcetacoplan commencement and after 3 months: 91 g/L and 205 × 109/L and 115.8 g/L and 107 × 109/L, respectively, resulting in mean Hb change of 22.3 g/L. Mean LDH pre- and post-pegcetacoplan was unchanged. Six patients have stopped pegcetacoplan. A total of 32 breakthrough hemolysis (BTH) events occurred in 13/48 patients. A total of 14 events were within clinical trials (reported separately). Six patients experienced 18 acute BTH events outside clinical trials, 7/18 associated with complement activating conditions. Successful clinical management included daily pegcetacoplan subcutaneously for 3 days or single eculizumab doses; these events are manageable with prompt intervention. Pegcetacoplan is effective for patients with PNH experiencing EVH. In this large patient cohort, treatment was well tolerated with improved hemoglobin and reticulocytes and maintained LDH control. Although BTH occurs, this is manageable by acute dose modification, with the majority of patients being maintained on pegcetacoplan.

The Prospective Effects of Coping Strategies on Mental Health and Resilience at Five Months after HSCT.

OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) is a stressful event that engenders psychological distress. This study examines the prospective effects of coping strategies during hospitalization on resilience and on various mental-health dimensions at five months after transplantation. METHODS: One hundred and seventy patients (Mage = 52.24, SD = 13.25) completed a questionnaire assessing adjustment strategies during hospitalization, and 91 filled out a questionnaire five months after HSCT (Mage = 51.61, SD = 12.93). RESULTS: Multiple regression analyses showed that a fighting spirit strategy positively predicted resilience (p < 0.05), whereas anxious preoccupations predicted anxiety (p < 0.05), poorer mental QoL (p < 0.01), and were associated with an increased risk of developing PTSD (OR = 3.27, p < 0.01; 95% CI: 1.36, 7.84) at five months after transplantation. Hopelessness, avoidance, and denial coping strategies were not predictive of any of the mental health outcomes. Finally, the number of transplantations was negatively related to a fighting spirit (p < 0.01) and positively related to hopelessness-helplessness (p < 0.001): Conclusions: These results highlight the importance of developing psychological interventions focused on coping to alleviate the negative psychological consequences of HSCT.

Mental health and quality of life of patients undergoing hematopoietic stem cell transplantation (HSCT) prior to hospitalization: a cross-sectional complete state health study.

OBJECTIVE: The main goal of this cross-sectional study was to examine the relationships between negative/positive psychological dispositions, mental health, and quality of life (QoL) prior to hospitalization among patients undergoing hematopoietic stem cell transplantation (HSCT). METHOD: A total of 187 patients (Mage = 52.07 years) completed a questionnaire 19.6 days before an allograft. Several positive psychological dispositions (i.e. mindfulness, optimism, and acceptance) and a negative psychological disposition (i.e. experiential avoidance) were assessed. Our dependent variables were mental health (i.e. happiness, depression, and anxiety) and QoL. RESULTS: In the sample, 56.8% of patients were characterized by an impaired QoL and 56.9% and 21% had, respectively, anxiety and depression levels above the critical threshold (i.e. a score above seven on the Hospital Anxiety and Depression Scale). Anxiety, depression, and happiness were significantly related to the mental component of QoL, whereas physical QoL was only related to depression and happiness. Providing additional support for a complete state health approach, several positive and negative psychological dispositions (i.e. optimism, acceptance, and experiential avoidance) were robustly related to mental illness/wellness and QoL. CONCLUSIONS: These results highlight the importance of improving psychological health and QoL among HSCT patients prior to hospitalization by both promoting positive psychological and health factors and alleviating negative ones.

Retrospective and prospective measures of post-traumatic growth reflect different processes: longitudinal evidence of greater decline than growth following a hematopoietic stem-cell transplantation.

BACKGROUND: This prospective longitudinal study examined and compared two measures (prospective and retrospective ones) of post-traumatic growth (PTG) following Hematopoietic Stem-Cell Transplantation (HSCT) and their respective relationships with mental health and psychological disposition. We also tested the hypothesis that unwillingness to be in contact with distressing thoughts and feelings-i.e. experiential avoidance-would moderate the relationship between Post-Traumatic Stress Disorder (PTSD) and growth. METHODS: This study was carried out with 187 patients. Patients completed the Post-Traumatic Growth Inventory (PTGI) 5 months after HSCT and scales tapping into the five domains of PTGI during hospitalisation and 5 months after HSCT. Mental health and psychological disposition were also assessed prior to hospitalisation. A PTSD scale was administered at the five-month follow-up. RESULTS: Prospective and retrospective measures of PTG were weakly correlated. Bayesian pre/post-HSCT comparisons in the prospective measure of PTG revealed substantial to very strong decline in four of the five dimensions assessed. Overall, RCI indicated a reliable increase for 5.6% of patients and a reliable decrease for 40.8% of patients. Confirming that retrospective and prospective measures of PTG reflect different processes, they were not related to the same mental health and psychological disposition variables. Moreover, the hypothesis that acquiring positive outcomes from a potentially traumatic experience, such as HSCT, requires direct confrontation with the source of distress was supported in the case of the retrospective measure of growth but not in the case of the prospective measure growth. CONCLUSIONS: Retrospective measures such as the PTGI do not appear to assess actual pre- to post-HSCT change. HSCT seems more linked to psychological decline than to growth.

Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial.

BACKGROUND: In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. METHODS/DESIGN: PRODIGE 22--ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50% prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial. TRIAL REGISTRATION: NCT01675999 (ClinicalTrials.gov).