Author
Lydia Roy
Other affiliations: University of Poitiers, French Institute of Health and Medical Research, Centre national de la recherche scientifique ...read more
Bio: Lydia Roy is an academic researcher from University of Paris. The author has contributed to research in topics: Imatinib mesylate & Imatinib. The author has an hindex of 28, co-authored 107 publications receiving 3688 citations. Previous affiliations of Lydia Roy include University of Poitiers & French Institute of Health and Medical Research.
Papers published on a yearly basis
Papers
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Heidelberg University1, University of Bologna2, Oregon Health & Science University3, Imperial College London4, Princess Margaret Cancer Centre5, University of Medicine and Dentistry of New Jersey6, Lille University of Science and Technology7, University of California, San Francisco8, University of Barcelona9, Cornell University10, Leipzig University11, Harvard University12, University of Paris13, University of Chicago14, Bristol-Myers Squibb15, University of Texas MD Anderson Cancer Center16
TL;DR: Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML, and it is shown that this drug is effective for patients with chronic myelogenous leukemia resistant or intolerant toImatinib.
Abstract: Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, <1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity (any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.
358 citations
TL;DR: Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR, and should be a criterion for resuming therapy.
Abstract: Purpose More than half of patients with chronic-phase chronic myelogenous leukemia (CP-CML) in complete molecular response (CMR) experience molecular relapse after imatinib discontinuation. We investigated loss of major molecular response (MMR) as a criterion for resuming therapy. Patients and Methods A multicenter observational study (A-STIM [According to Stop Imatinib]) evaluating MMR persistence was conducted in 80 patients with CP-CML who had stopped imatinib after prolonged CMR. Results Median time from imatinib initiation to discontinuation was 79 months (range, 30 to 145 months);median duration of CMR before imatinib discontinuation was 41 months (range, 24 to 96 months); median follow-up after discontinuation was 31 months (range, 8 to 92 months). Twenty-nine patients (36%) lost MMR after a median of 4 months off therapy (range, 2 to 17 months). Cumulative incidence of MMR loss was estimated as 35% (95% CI, 25% to 46%) at 12 months and 36% (95% CI, 26% to 47%) at 24 months, whereas probability of ...
346 citations
Mayo Clinic1, University of Paris2, VU University Amsterdam3, Erasmus University Rotterdam4, Leiden University5, Maastricht University6, Autonomous University of Madrid7, University of Freiburg8, University of Ulm9, University of Basel10, University of Angers11, University of Bordeaux12, Joseph Fourier University13, Guy's and St Thomas' NHS Foundation Trust14, British Hospital15, University of Puerto Rico16, Pompeu Fabra University17, University of Barcelona18, University of Florence19, University of Pavia20, Karolinska Institutet21, Uppsala University22
TL;DR: The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptoms study to date.
Abstract: Purpose Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. Patients and Methods The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Results MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P < .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) f...
321 citations
TL;DR: There is a survival advantage from first-line therapy with imatinib over IFN/Ara-C over interferon plus cytarabine, and improved overall survival was also confirmed within different Sokal prognostic risk groups.
223 citations
TL;DR: P-loop and T315I mutations selectively impair the outcome ofImatinib-resistant CML patients, in contrast to other mutations, which may benefit from dose escalation of imatinib, able to improve or stabilize disease response.
Abstract: The emergence of ABL point mutations is the most frequent cause for imatinib resistance in chronic myelogenous leukemia (CML) patients and can occur during any phase of the disease; however, their clinical impact remains controversial. In this study, we retrospectively analyzed the predictive impact of 94 BCR-ABL kinase domain mutations (18 T315I, 26 P-loop, 50 in other sites) found in 89 imatinib-resistant CML patients. At imatinib onset, 64% of patients (57/89) were in chronic phase (CP), 24% (21/89) in accelerated phase (AP) and 12% (11/89) in blastic phase (BP). T315I and P-loop mutations were preferentially discovered in accelerated phase of BP CML, and other types of mutations in CP (P=0.003). With a median follow-up of 39.2 months (6.3-67.2), since imatinib initiation, overall survival (OS) was significantly worse for P-loop (28.3 months) and for T315I (12.6 months), and not reached for other mutations (P=0.0004). For CP only, multivariate analysis demonstrated a worse OS for P-loop mutations (P=0.014), and a worse progression-free survival (PFS) for T315I mutations (P=0.014). Therefore, P-loop and T315I mutations selectively impair the outcome of imatinib-resistant CML patients, in contrast to other mutations, which may benefit from dose escalation of imatinib, able to improve or stabilize disease response.
214 citations
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Oregon Health & Science University1, Newcastle University2, Novartis3, University of Texas MD Anderson Cancer Center4, University of Düsseldorf5, Leipzig University6, Cornell University7, National Institutes of Health8, Harvard University9, University of Barcelona10, Heidelberg University11, Wake Forest University12, Icahn School of Medicine at Mount Sinai13, University of Paris14, University of Bordeaux15, Erasmus University Rotterdam16, Royal Adelaide Hospital17, Medical University of Vienna18, University of Mainz19, Katholieke Universiteit Leuven20, University of British Columbia21, University of Basel22, Aarhus University23, Fred Hutchinson Cancer Research Center24, Uppsala University25, Mater Health Services26, University of Bologna27, University of Chicago28
TL;DR: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients.
Abstract: BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...
3,351 citations
TL;DR: It is found that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role, and this analysis extended to other cancer-related genes that possess pseudogenes, and revealed a non-coding function for mRNAs.
Abstract: The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
2,107 citations
University of Bologna1, University of Utah2, University of Jena3, Imperial College London4, University of Barcelona5, Royal Liverpool and Broadgreen University Hospital NHS Trust6, University of Texas MD Anderson Cancer Center7, University of Poitiers8, Norwegian University of Science and Technology9, University of Adelaide10, Catholic University of Korea11, University of Chicago12, University of Toronto13, University of Bordeaux14, Masaryk University15, Heidelberg University16, Leipzig University17, University of Naples Federico II18, Fred Hutchinson Cancer Research Center19, University of Turin20, Wayne State University21, Cornell University22, Uppsala University23
TL;DR: Optimal responders to chronic myeloid leukemia treatment should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
1,679 citations
University of Alabama at Birmingham1, University of South Florida2, Vanderbilt University3, City of Hope National Medical Center4, Fox Chase Cancer Center5, University Of Tennessee System6, Brigham and Women's Hospital7, Seattle Cancer Care Alliance8, Case Western Reserve University9, Roswell Park Cancer Institute10, Northwestern University11, Harvard University12, University of Nebraska Medical Center13, University of Utah14, Memorial Sloan Kettering Cancer Center15
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
1,545 citations
TL;DR: Since achieving complete cytogenetic response within 12 months has been associated with better long-term, progression-free survival, dasatinib may improve the long- term outcomes among patients with newly diagnosed chronic-phase CML.
Abstract: Background Treatment with dasatinib, a highly potent BCR-ABL kinase inhibitor, has resulted in high rates of complete cytogenetic response and progression-free survival among patients with chronic myeloid leukemia (CML) in the chronic phase, after failure of imatinib treatment. We assessed the efficacy and safety of dasatinib, as compared with imatinib, for the first-line treatment of chronic-phase CML. Methods In a multinational study, 519 patients with newly diagnosed chronic-phase CML were randomly assigned to receive dasatinib at a dose of 100 mg once daily (259 patients) or imatinib at a dose of 400 mg once daily (260 patients). The primary end point was complete cytogenetic response by 12 months, confirmed on two consecutive assessments at least 28 days apart. Secondary end points, including major molecular response, were tested at a significance level of 0.0001 to adjust for multiple comparisons. Results After a minimum follow-up of 12 months, the rate of confirmed complete cytogenetic response was higher with dasatinib than with imatinib (77% vs. 66%, P = 0.007), as was the rate of complete cytogenetic response observed on at least one assessment (83% vs. 72%, P = 0.001). The rate of major molecular response was higher with dasatinib than with imatinib (46% vs. 28%, P<0.0001), and responses were achieved in a shorter time with dasatinib (P<0.0001). Progression to the accelerated or blastic phase of CML occurred in 5 patients who were receiving dasatinib (1.9%) and in 9 patients who were receiving imatinib (3.5%). The safety profiles of the two treatments were similar. Conclusions Dasatinib, administered once daily, as compared with imatinib, administered once daily, induced significantly higher and faster rates of complete cytogenetic response and major molecular response. Since achieving complete cytogenetic response within 12 months has been associated with better long-term, progression-free survival, dasatinib may improve the long-term outcomes among patients with newly diagnosed chronic-phase CML. (ClinicalTrials.gov number, NCT00481247.)
1,386 citations