Dasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study).

Superior rates of deep molecular response (DMR) have been reported with the combination of tyrosine kinase inhibitors and pegylated-interferon-alpha (Peg-IFN) in patients with newly diagnosed chronic phase-chronic myeloid leukaemia (CP-CML). In this setting, this study investigated the efficacy and safety of dasatinib combined to Peg-IFN-α2b (Dasa-PegIFN, NCT01872442). A total of 79 patients (age ≤65 years) started dasatinib; 61 were eligible for Peg-IFNα-2b add-on therapy at month 3 for a maximum 21-months duration. Dasatinib was continued thereafter. The primary endpoint was the cumulative rate of molecular response 4.5 log (MR4.5 ) by 12 months. The results are reported for the 5-year duration of the study. Grade 3 neutropenia was frequent with the combination but did not induce severe infection (one of grade 3). Other adverse events were generally low grade (4% of grade 3-4) and expected. Seventy-nine per cent and 61% of patients continued the Peg-IFN until months 12 and 24, respectively. Overall, at these time points, MR4.5 rates were 25% and 38%, respectively. Thereafter, 32% and 46% of patients achieved a sustained (≥2 years) MR4.5 or MR4 , respectively. This work established the feasibility and high rates of achievement of early and sustained DMR (a prerequisite for treatment-free-remission) with dasatinib and Peg-IFNα-2b combination as initial therapy.

A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients with polycythemia vera or essential thrombocythemia.

Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis. This phase 2, open-label, randomized study evaluated the efficacy and safety of oral once-daily momelotinib (100mg and 200mg) for the treatment of polycythemia vera (PV) and essential thrombocythemia (ET). The primary endpoint for PV was overall response rate (ORR), defined as the proportion of patients with hematocrit <45%, white blood cell count <10×109/L, platelet count ≤400×109/L, and resolution of palpable splenomegaly, each lasting ≥4 weeks. The definition of ORR for ET excluded the hematocrit component. A total of 39 patients (28 PV, 11 ET) were enrolled, with 28 patients receiving ≥12 weeks of treatment. The study was terminated due to limited efficacy. Two patients (ORR 5.1%) met the primary efficacy endpoint (both PV 200mg). Predose plasma levels of momelotinib were stable over time. A total of 31 (79.5%) patients experienced momelotinib-related adverse events (AEs), the most frequent being headache (23.1%), dizziness (18.0%), somnolence (15.4%), nausea (15.4%), and fatigue (15.4%). Three patients experienced serious AEs (7.7%), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy occurred in 7 (17.9%) patients (4 PV, 3 ET).

High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study.

The optimal management of relapsed diffuse large B-cell lymphoma (DLBCL) is not standardized. The Groupe Ouest Est des Leucémies et aAutres Maladies du Sang developed a combination of vinorelbine, ifosfamide, mitoxantrone and prednisone (NIMP) for the treatment of relapsed DLBCL, and assessed its efficacy and safety in association with rituximab (R). This multicentric phase II study included 50 patients with DLBCL in first relapse, aged 18-75 years. Patients received rituximab 375 mg/m² day 1, ifosfamide 1000 mg/m² days 1-5, vinorelbine 25 mg/m² days 1 and 15, mitoxantrone 10 mg/m² day 1, and prednisone 1 mg/kg days 1-5, every 28 days for three cycles. Responding patients underwent autologous transplantation or received three additional R-NIMP cycles. All patients were evaluable for toxicity and 49 for response. Centralized pathology review confirmed DLBCL in all cases. Toxicities were mainly haematological with infectious events needing hospitalization in nine cases. Two toxic deaths were observed. After three cycles, 22 patients (44%) achieved complete response/unconfirmed complete response, 11 achieved partial response (24%), 2 had stable disease and 13 progressed. The non-germinal centre B immunophenotype was associated with shorter progression-free survival. in conclusion, the R-NIMP regimen displayed significant activity in relapsed DLBCL, with acceptable toxicity and should be considered a candidate for combination with new agents.

[Multidisciplinary team meetings in cancerology: setting priorities for improvement]. / Évaluation des réunions de concertation pluridisciplinaire en cancérologie : quelles priorités pour quelles améliorations ?

Resulting medical decision from a multidisciplinary team (MDT) meeting has to be accurate regarding to various patient criteria and relevant specialists participation. The target is to optimize treatment or management options for patients taking into account patients' benefit. The aim of our study was to examine quality criteria of MDT meeting processes, implementation of the MDT decision, and the follow-up of national or regional clinical guidelines. The results lead us to discuss about care management in cancer. Ten various medical specialities of MDT meetings were studied. Relevant multidisciplinarity varied between MDT meetings specialities and was effective between 55 and 100%. Implementation of the decisions that arise from MDT meetings was 86.3%. The most frequent grounds of non-application were patient refusal and new or previous unknown clinical data. The percentage of MDT meetings decisions following national or regional recommendations was 74%. The main reason of not following was the complexity of clinical patient circumstances. Participation in MDT meetings is more and more time-consuming related to enforce the completeness referred to the Plan Cancer (National recommendations). Leading to completeness raises questions about medical time employment and meaning of the MDT meeting for standard clinical cases. The priority seems to enforce multidisciplinarity rather than reach completeness.

Therapeutic impact and diagnostic performance of multiplex PCR in patients with malignancies and suspected sepsis.

OBJECTIVES: New molecular methods allow rapid pathogen detection in patients with sepsis, but their impact on treatment decisions remains to be established. We evaluated the therapeutic usefulness of multiplex PCR testing in patients with cancer and sepsis. METHODS: 110 patients with cancer and sepsis were included prospectively and underwent LightCycler® SeptiFast (LC-SF) multiplex PCR testing in addition to standard tests. Two independent panels of experts assessed the diagnosis in each patient based on medical record data; only one panel had the LC-SF results. The final diagnosis established by a third panel was the reference standard. RESULTS: The final diagnosis was documented sepsis in 50 patients (55 microorganisms), undocumented sepsis in 54, and non-infectious disease in 6. LC-SF detected 17/32 pathogens recovered from blood cultures (BC) and 11/23 pathogens not recovered from BC; 12 microorganisms were detected neither by BC nor by LC-SF. LC-SF produced false-positive results in 10 cases. The LC-SF results would have significantly improved treatment in 11 (10%) patients and prompted immediate antimicrobial therapy not given initially in 3 patients. CONCLUSIONS: In cancer patients with suspected sepsis, LC-SF detected 11/55 (20%) true pathogens not recovered from BCs and would have improved the initial management in 11/110 (10%) patients.

Two new alpha-thalassemia point mutations that are undetectable by biochemical techniques.

We report two new point mutations causing alpha-thalassemia (alpha-thal) that could not be characterized by conventional biochemical studies. The first mutation is a single base substitution at codon 123 of the alpha1-globin gene [alpha123(H6)Ala-->Pro, GCC>CCC (alpha1)] and leads to the substitution of a proline residue in the H helix. The resulting unstable hemoglobin (Hb) variant has been named Hb Voreppe. The second is a frameshift of the alpha2 gene due to a deletion (-C), either of the third base of codon 112 or of the first base of codon 113, that causes a premature stop codon at position 132.