Successful Imatinib therapy as a bridge to transplant in an atypical myeloproliferative neoplasm

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18 F-Fludarabine PET for Lymphoma Imaging: First-in-Humans Study on DLBCL and CLL Patients

CERVOXY/LDM-TEP COLLInternational audienceThis was the first-in-humans clinical study of 18F-fludarabine, which is a radiopharmaceutical for PET imaging in lymphoma, for which many issues remain controversial with the standard radiotracer 18F-FDG. Methods: 18F-fludarabine PET or PET/CT was performed on 10 patients: 5 with diffuse large B-cell lymphoma (DLBCL) and 5 with chronic lymphocytic leukemia. The tumor uptake, biodistribution, and radiation dosimetry of 18F-fludarabine were evaluated. Six successive partial-body PET scans were acquired for 250 min after an intravenous 4 MBq/kg bolus of 18F-fludarabine. SUVs were recorded for each involved lymph node territory and for several extranodal sites, with particular reference to the liver. To assess the time-related uptake profile of 18F-fludarabine, PET images were analyzed by delineating volumes of interest over the uptake sites on the optimal scan for visual observation and were projected onto all coregistered scans of the same subject. Physical examination, laboratory studies, and contrast-enhanced CT were performed on all patients. For the DLBCL group, 18F-FDG PET was also considered. Results: In DLBCL patients, increased 18F-fludarabine uptake was observed in sites considered abnormal by CT or 18F-FDG, with SUVs significantly higher in involved lesions than in physiologic nontarget sites. Nonetheless, the comparison of 18F-fludarabine and 18F-FDG PET showed discrepancies in 2 patients. In chronic lymphocytic leukemia patients, the uptake of 18F-fludarabine coincided with sites expected to be involved (including splenic invasion) according to conventional clinical and CT staging and was significant in hematopoietic bone marrow. No uptake was observed, whatever the disease group, in cardiac muscle or brain. The mean effective dose from a mean injected 18F-fludarabine activity of 305 ± 76 MBq was 3.07 ± 0.81 mSv. Conclusion: 18F-fludarabine PET might well be a promising tool for lymphoproliferative diseases. The radiation dose of this radiopharmaceutical is below that of 18F-FDG. The specificity of this PET probe for lymphoid cells, its absence of accumulation in reactive tissues, and its feasibility for detection of bone marrow infiltration might play an innovative role in lymphoma imaging

Ibrutinib in very elderly patients with relapsed/refractory chronic lymphocytic leukemia: A real-world experience of 71 patients treated in France: A study from the French Innovative Leukemia Organization (FILO) group

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Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

International audienceBackground There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation. DESIGN AND METHODS: Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed. RESULTS: The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3-4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3-4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively. Conclusions The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: NCT00285389)

Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

International audienceAims: The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF.Methods and results: A disproportionality analysis evaluating the multivariable adjusted reporting odd-ratios (aROR) for AF with their 99.97% confidence intervals (CI) was performed for 176 FDA- or EMA-labeled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215.A total of 11,757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in hematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane) and obinutuzumab, an anti-CD20 monoclonal antibody.Conclusion: Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of hematologic malignancies

Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95

International audiencePeripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear as highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite non satisfactory results with the CHOP regimen, it remains the reference front line therapy in these diseases, but has not been challenged in phase III trials. The GOELAMS group devised an alternative therapeutic schedule including Etoposide, Ifosfamide, Cisplatin alternating with Doxorubicin, Bleomycin, Vinblastin, Dacarbazine (VIP-reinforced-ABVD) and compared it to CHOP/21 as front-line treatment in non cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-years event-free survival (EFS) rate. Secondary objectives were to compare the response rates, overall survival, and toxicities as well as identify prognostic factors. 88 patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-years EFS. ALCL type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. The VIP-rABVD regimen was not superior to CHOP/21 in term of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference arm in these lymphomas

Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia

International audienceElderly patients with chronic lymphocytic leukemia (CLL) are underrepresented in trials evaluating fludarabine, cyclophosphamide, and rituximab (FCR). We assessed four cycles of FCR with two additional rituximab doses on day 14 of cycles 1 and 2 in 194 untreated CLL patients \textgreater 65 years (median age 71.2) without del17p. Four FCR cycles were administered to 90.7% (176/194), with (n = 74) or without (n = 102) dose-delay and/or dose-reduction. A total of 50% grade 3/4 neutropenia occurred after each cycle. Only 6.2% cycles were associated with severe infection. Complete remission (CR) was achieved in 19.7%, and partial remission (PR) in 73.9% of patients. Minimal residual disease (MRD) was negative in 36.7%. Overall survival at 36 months was estimated at 87.4%. Oral FC and dose-dense rituximab is feasible and active in fit elderly CLL patients. However, myelosuppression is significant and frequent dose adaptations are required implying that these results cannot be generalized to unfit or frail elderly CL