Kinetics of early and late molecular recurrences after first-line imatinib cessation in chronic myeloid leukemia: updated results from the STIM2 trial

Discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia is feasible in clinical practice based on recently published international recommendations. Nevertheless, factors predictive of molecular recurrence have not been fully elucidated and long-term follow-up of patients enrolled in clinical studies are required in order to update knowledge on discontinuation attempts particularly in terms of the safety and durability of treatment-free remission (TFR). In the current study, we updated results from the STIM2 study in the light of the consensual criterion of molecular recurrence reported in different international recommendations. Among the 199 patients included in the perprotocol study, 108 patients lost a major molecular response. With a median follow-up of 40.8 months (5.5-111 months), the probability of treatment-free remission was 43.4% [36.3-50.4] at 5 years, 40.9% [32.8-47.3] at 7 years and 34.5% [25.6- 43.3] at 9 years. Molecular recurrence occurred between 0 to 6 months, 6 to 24 months and after 24 months in 75 patients (69%), 15 patients (14%) and 18 patients (17%), respectively. Notably, the kinetics of molecular recurrence differed significantly between these three subgroups with a median time from loss of MR4 (BCR::ABL1 IS≤0.01%) to loss of major molecular response of 1, 7 and 22 months, respectively. Predictive factors of molecular recurrence differed according to the time of occurrence of the molecular recurrence. Durations of imatinib treatment and deep molecular response as well as BCR::ABL1/ABL1 levels at cessation of tyrosine kinase inhibitor treatment, as quantified by reverse transcriptase droplet digital polymerase chain reaction, are involved in molecular recurrence occurring up to 24 months but not beyond. (ClinicalTrial. gov Identifier NCT#0134373)

Evaluation par recherche du réaménagement BCL2/IGH de la maladie résiduelle dans les intensifications thérapeutiques

La détection du réarrangement Bcl2/IgH par méthode de PCR est utile pour suivre la maladie résiduelle des lymphomes folliculaires et folliculaires transformés ainsi que pour mettre en évidence une éventuelle contamination du greffon lors des intensifications thérapeutiques. Seize malades ont été étudiés. La présence de cellules portant le réarrangement Bcl2/IgH dans le greffon n'est pas toujours associé à la rechute. La présence de cellules portant le réarrangement Bcl2/IgH après intensification est de mauvais pronostic. Toutefois, elle peut ne pas être associée à une rechute. Quatre des cinq malades en rémission complète trois ans après la greffe ont bénéficié d'un greffon avec sélection CD34.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Momelotinib long-term safety and survival in myelofibrosis : integrated analysis of phase 3 randomized controlled trials

Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor-naive) to late (JAK inhibitor-experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY-2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for ≥5 years, with a median treatment exposure of 11.3 months (range, 0.1-90.4 months). The most common nonhematologic treatment-emergent adverse event (AE) occurring in ≥20% of patients was diarrhea (any grade, 27% and grade ≥3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity

Prognostic value of interim FDG PET/CT in Hodgkin's lymphoma patients treated with interim response-adapted strategy: comparison of International Harmonization Project (IHP), Gallamini and London criteria.

International audiencePURPOSE: Interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has shown to be an accurate predictor of prognosis in Hodgkin's lymphoma (HL). However, FDG PET response criteria are a matter of ongoing debate. The aim of this study was to confirm the prognostic value of interim PET/CT in HL patients treated with an interim response-adapted strategy and to compare the respective performances of different published criteria. METHODS: Newly diagnosed patients with HL underwent interim PET/CT after four courses of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The treatment strategy was adapted according to prognostic factors at diagnosis and interim PET/CT and CT results. PET images were prospectively interpreted visually: a negative result was defined as no residual uptake above local background. All other findings were considered as positive. Retrospectively, interim PET/CT was analysed according to International Harmonization Project (IHP), Gallamini and London criteria RESULTS: The analysis included 90 patients; 6 of 31 patients with positive interim PET/CT and 7 of 59 patients with negative interim result presented treatment failure. The negative predictive value (NPV) and positive predictive value (PPV) for predicting 2-year progression-free survival (PFS) was 95 and 16%, respectively. With the other criteria, NPV remained very high (from 95 to 96%). The PPV increased from 19 to 45% according to the threshold used. Interim PET/CT was significantly correlated with PFS with Gallamini (p = 0.01) and London criteria (p < 0.0001). CONCLUSION: Our study confirms the high NPV of interim PET/CT for predicting treatment outcome in HL and a probably better prognostic value using a higher threshold for positivity even after four cycles of chemotherapy as used in Gallamini and London criteria

Biological differences between two commercial anti-CD19 CAR T cells products and impact on outcomes in lymphoma patients.

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Late Complications and Quality of Life after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation

International audienceLate complications (LC) and quality of life (QOL) were analyzed in 110 adult patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) and were alive for more than 2 years after allo-SCT. Overall survival of these patients was 93% (95% confidence interval [CI], 88% to 99%) and 81% (95% CI, 71% to 94%) at 5 and 10 years, respectively. The primary cause of death was a recurrence of primary malignancy. With a median follow-up of 4.6 years (range, 2 to 12.1), chronic graft-versus-host disease (cGVHD) was the most prevalent late effect, with a cumulative incidence of 66% (95% CI, 57% to 74%) at 10 years. Car-diovascular complications were the most prevalent LC with a cumulative incidence of 47% (95% CI, 35% to 59%), followed by pulmonary complications with a cumulative incidence of 33% (95% CI, 21% to 46%) and renal impairment with a cumulative incidence of 34% (95% CI, 25% to 43%) at 10 years. Secondary malignancies occurred with a cumulative incidence of 11% (95% CI, 5% to 20%) at 10 years. In this series, 61 patients (55%) responded to QOL survey. With the use of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 and Functional Assessment of Cancer Therapy–Bone Marrow Transplant questionnaires , most of the patients reported good to excellent QOL and patients with cGVHD had significantly lower QOL than patients without cGVHD. In conclusion, QOL after RIC is comparable to that seen after myeloablative conditioning, while the natural history of LC after RIC appears to be different from that described in the standard myeloablative setting, warranting further research in this field