PD-1 blockade and allogeneic hematopoietic stem cell transplantation in Hodgkin lymphoma, a matter of time: a national study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

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Safety profile of immune checkpoint inhibitors according to cancer type.

INTRODUCTION: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment in recent years, but have led to the emergence of new so-called immune-related adverse events (irAE). The objective of this study was to determine whether cancer type is a potential predictive factor of irAEs. METHODS: This retrospective study included patients who had started an ICI treatment between 2019 and 2020 at the Grenoble Alpes University Hospital. A logistic regression model and a Fine and Gray survival model with death as a competing risk were used to identify variables associated with grade≥2 irAEs and grade≥2 irAEs-free survival. RESULTS: Of the 512 patients included, 160 (31.2%) had a grade≥2 irAE. Grade≥2 irAEs were less frequent in head and neck cancer compared to other cancers. Ipilimumab (odds ratio [OR]: 6.05; 95% confidence interval [CI]: 2.81-13.7), treatment duration (OR: 1.01; 95% CI: 1.01-1.02), and history of autoimmune disease (OR: 6.04; 95% CI: 2.45-16.5) were independently associated with grade≥2 irAEs. With death as a competing risk, grade≥2 irAEs-free survival was independently improved with treatment duration (subdistribution hazard ratio [sdHR]: 0.93; 95% CI: 0.92-0.94), ipilimumab (sdHR: 0.24; 95% CI: 0.1-0.59) and history of autoimmune disease (sdHR: 0.23; 95% CI: 0.08-0.69) whereas it was poorer for patients with performance status≥2 (sdHR: 2.04; 95% CI: 1.5-2.76) and an older age (sdHR: 1.02; 95% CI: 1.00-1.03). CONCLUSION: Ipilimumab and history of autoimmune disease were both associated with the presence of grade≥2 irAEs and grade≥2 irAEs-free survival. The different cancer groups were not.

Impact of extended interval dosing of immune checkpoint inhibitors in lung cancer patients during the COVID-19 pandemic.

BACKGROUND: The COVID 19-pandemic has led physicians to change their approach to treating non-small cell lung cancer (NSCLC) to reduce hospital stays for patients. OBJECTIVES: We aimed to assess the toxicity and efficacy of extended interval (EI) dosing of immune checkpoint inhibitors (ICIs) compared to standard dosing (SD). METHODS: In this retrospective two-center study, we included patients with stage III/IV NSCLC who were treated with ICIs with or without maintenance pemetrexed during the month before March 2020. Adverse events and efficacy were collected until June 2021. Toxicity and survival were assessed using multivariate Cox models. RESULTS: Among the 134 patients identified (8 stage III and 126 stage IV; 66 first line and 60 second or subsequent lines), 70.9% received EI dosing. In the EI group, 12.6% of patients developed grade 3 or 4 immune-related adverse events versus 15.4% in the SD group (P- value = 0.8). Treatment was definitively discontinued due to toxicity in 9 patients in the EI group and in 5 in the SD group (P-value =0.5). Overall survival was not associated with dosage regimen or toxicity analyzed as a time-dependent variable. CONCLUSIONS: Our study suggests that EI dosing of ICIs did not affect toxicity and overall survival in lung cancer patients.

Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

Late relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity.

Quality of life of patients with solid malignancies at 3 months after unplanned admission in the intensive care unit: A prospective case-control study.

BACKGROUND: Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. METHODS: A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 1:2 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. RESULTS: In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients: median of 54 (interquartile range: 42-57) vs. 47 (37-52), respectively (p = 0.01). The physical component score of the SF-36 did not differ between groups: 35 (31-47) vs. 42 (34-47) (p = 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. CONCLUSION: In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients.