Anne-Sophie Michallet

BACKGROUND Despite significant improvements in cancer survival, late complications from oncological treatments remain inadequately managed in routine clinical practice. Standard oncology follow-up prioritizes disease recurrence detection over systematic assessment of treatment-related sequelae, resulting in underdiagnosis of physical, psychological, metabolic, and social complications that substantially impair survivors' quality of life. The temporal dynamics of complication emergence remain poorly characterized, limiting development of evidence-based surveillance schedules. Objective: This study aims to determine the time-specific incidence of 19 predefined treatment-related complications at 1, 6, 24, and 60 months following completion of first-line chemotherapy in adult cancer survivors who achieved complete response. Secondary objectives include characterizing temporal trajectories to identify critical surveillance windows, evaluating the feasibility and performance of a standardized guideline-based referral system integrated within a regional healthcare network, and identifying predictive factors for complication occurrence and timing. OBJECTIVE This study aims to determine the time-specific incidence of 19 predefined treatment-related complications at 1, 6, 24, and 60 months following completion of first-line chemotherapy in adult cancer survivors who achieved complete response. Secondary objectives include characterizing temporal trajectories to identify critical surveillance windows, evaluating the feasibility and performance of a standardized guideline-based referral system integrated within a regional healthcare network, and identifying predictive factors for complication occurrence and timing. METHODS PASCA-c is a single-center, prospective, interventional cohort study conducted at Centre Léon Bérard (Lyon, France). Over 36 months, 500 adults aged 18–65 years with complete responses to first-line therapy for lymphomas (Hodgkin/non-Hodgkin), acute myeloid leukemia, testicular germ cell tumors, non-metastatic breast cancer, or sarcomas will undergo systematic screening at 1 month (T1), 6 months (T2), 24 months (T3), and 60 months (T4) post-treatment. Each assessment includes validated questionnaires, biomarker analyses, cardiovascular evaluations, spirometry, and functional performance tests covering 19 complication domains. Clinical decision trees based on French and international guidelines generate standardized referral recommendations. Patients are referred to a regional network of 120+ healthcare professionals for complication management while continuing standard oncological follow-up. The primary outcome is the time-specific incidence of each complication at T1, T2, T3, and T4, distinguishing new-onset cases from persistent complications detected at prior assessments. RESULTS Patient enrollment began in September 2020 and is ongoing. Final results are anticipated in 2027 upon completion of 60-month follow-up assessments for the last enrolled participant. CONCLUSIONS PASCA-c represents the first large-scale European study systematically evaluating the temporal dynamics of 19 treatment-related complications across multiple cancer types. By characterizing time-specific incidence patterns, this study will identify critical surveillance windows for each complication, informing the development of evidence-based, temporally-optimized survivorship care protocols that can be adapted to diverse healthcare settings. CLINICALTRIAL The study protocol (version_3_03-15-2022) was approved by the French ethics committee (Comité de protection des personnes Ile de France IV, ID-RCB: 2020-A01130-39). The study is registered on ClinicalTrials.gov (NCT04052126). All participants will be asked to sign and date an informed consent form. The results will be published in peer-reviewed journals and academic conferences. The study data have been declared to the ‘Commission nationale de l'informatique et des libertés’ via the reference methodology MR-001 n° R201-001-006.

Chronic lymphocytic leukemia (CLL) is a B-cell-derived hematologic malignancy whose progression depends on active B-cell receptor (BCR) signaling. Despite the spectacular efficacy of Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), resistance can develop in CLL patients, and alternative therapeutic strategies are therefore required. Cancer immunotherapy has revolutionized cancer care and may be an attractive approach in this context. We speculated that characterizing the immune responses of CLL patients may highlight putative immunotherapeutic targets. Here, we used high-dimensional spectral flow cytometry to compare the distribution and phenotype of non-B-cell immune populations in the circulating blood of CLL patients treated with Ibrutinib displaying a complete response or secondary progression. Although no drastic changes were observed in the composition of their immune subsets, the Ibrutinib-resistant group showed increased cycling of CD8+ T cells, leading to their overabundance at the expense of dendritic cells. In addition, the expression of 11 different surface checkpoints was similar regardless of response status. Together, this suggests that CLL relapse upon Ibrutinib treatment may not lead to major alterations in the peripheral immune response.

Background: t‐AML occurs after a primary malignancy treatment and retains a poor prognosis.Aims: To determine the impact of primary malignancies, therapeutic strategies, and prognostic factors on clinical outcomes of t‐AML.Results: A total of 112 adult patients were included in this study. Fifty‐Five patients received intensive chemotherapy (IC), 33 non‐IC, and 24 best supportive care. At t‐AML diagnosis, 42% and 44% of patients presented an unfavorable karyotype and unfavorable 2010 ELN risk profile, respectively. Among treated patients (n = 88), 43 (49%) achieved complete remission: four out of 33 (12%) and 39 out of 55 (71%) in non‐IC and IC groups, respectively. With a median follow‐up of 5.5 months, the median overall survival (OS) and disease‐free survival (DFS) for the whole population were 9 months and 6.3 months, respectively, and for the 88 treated patients 13.5 months and 8.2 months, respectively. Univariate analysis on OS and DFS showed a significant impact of high white blood cells (WBC) and blast counts at diagnosis, unfavorable karyotype and ELN classification. Multivariate analysis showed a negative impact of WBC count at diagnosis and a positive impact of chemotherapy on OS and DFS in the whole population. It also showed a negative impact of previous auto‐HCT and high WBC count on OS and DFS and of IC on OS in treated patients which disappeared when we considered only confounding variables (age, previous cancers, marrow blasts, and 2010 ELN classification). In a pair‐matched analysis comparing IC treated t‐AML with de novo AML, there was no difference of OS and DFS between the two populations.Conclusion: We showed, in this study that t‐AML patients with unfavorable features represented almost half of the population. Best outcomes obtained in patients receiving IC must be balanced by known confounding variables and should be improved by using new innovative agents and therapeutic strategies.

Background: Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low‐dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real‐life conditions.Method: This retrospective, real‐life study collected data on venetoclax use and management in a French cohort with acute myeloid leukemia (AML) ineligible for intensive chemotherapy.Result: Of 118 patients, 81 were in second line/beyond (71.6% also hypomethylating agent [HMA]; 23.5% lowdose cytarabine [LDAC]) and 37 in first line. For venetoclax initiation, 57.3% underwent ramp up and 74.6% were hospitalized. Median venetoclax duration was 2.5 months (range 0.03‐16.2). With all treatment lines and regimens, most common grade 3/4 adverse events were hematologic (overall 96.4% of patients) and infections (57.1%). Dosage adjustments for drug interactions and safety varied between centers. In second‐line/beyond, median progression‐free survival was 4.0 months (95% confidence interval [CI] 2.7‐12.8) with venetoclax‐HMA and 3.4 months (1.3‐8.9) with venetoclax‐LDAC; overall response rate was 51.9% and 41.2%, respectively. Thus, we showed that venetoclax‐based treatment yields promising findings in patients with AML, but to address treatment complexity, practice harmonization is needed.

Context The need for patient navigator is growing, and there is a lack of cost evaluation, especially during survivorship. Objective The objective of this study is to evaluate the cost-effectiveness of an Ambulatory Medical Assistance (AMA) programme in patients with haematological malignancies (HM). Design A cost-effectiveness analysis of the AMA programme was performed compared to a simulated control arm. Setting An interventional, single-arm and prospective study was conducted in a French reference haematology-oncology centre between 2016 and 2020. Participants Adult patients were enrolled with histologically documented malignant haematology, during their active therapy phase, and treated either by intravenous chemotherapy or oral therapy. Methods An extrapolation of the effectiveness was derived from a similar nurse monitoring programme (CAPRI study). Cost effectiveness of the programme was evaluated through adverse events of Grade 3 or 4 avoided in different populations. Results Included patient (n = 797) from the AMA programme were followed during 125 days (IQR: 0-181), and adverse events (Grade 3/4) were observed in 10.1% of patients versus 13.4% in the simulated control arm. The overall cost of AE avoided was estimated to euro81,113, leading to an ICER of euro864. Conclusion The AMA programme was shown to be cost-effective compared to a simulated control arm with no intervention.