225 research outputs found
Blinatumomab consolidation and maintenance therapy in adults with relapsed/refractory B-precursor acute lymphoblastic leukemia
In a phase 3 clinical study of heavily pretreated adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), overall survival (OS) following blinatumomab, a BiTE (bispeci\ufb01c T-cell engager) immunooncology therapy, was signi\ufb01cantly improved vs chemotherapy following induction (cycles 1 to 2). Here we report the e\ufb03cacy and safety of those who received additional cycles of blinatumomab. Blinatumomab was administered as a continuous IV infusion for 4 weeks in a 6-week cycle. Patients who achieved a bone marrow response (#5% blasts) or complete remission (full, partial, or incomplete hematological recovery) during induction could receive additional cycles of blinatumomab. OS and relapse-free survival (RFS) for consolidation (cycles 3 to 5) vs no consolidation, and maintenance (cycles $6) vs no maintenance were analyzed using Simon-Makuch and Mantel-Byar odds ratios. Of 267 patients who received blinatumomab induction, 86 (32%) entered consolidation and 36 (13%) entered maintenance. Evidence of longer OS was demonstrated among the maintenance group compared with no-maintenance (median OS [95% con\ufb01dence interval, CI]: not reached for maintenance vs 15.5 months for no maintenance). Median RFS (months; 95% CI) was numerically longer among maintenance group (14.5; 7.1 to 21.9) compared with no-maintenance (9.8; 8.5 to 11.1). A lower incidence of adverse events was seen during maintenance (72.2%) compared with induction (97.2%) and consolidation (86.1%). Adults with R/R ALL who achieved remission following blinatumomab induction had longer survival on continuation therapy than those who discontinued blinatumomab early, supporting the use of blinatumomab as long-term therapy. No new safety signals were reported. This trial was registered at www.clinicaltrials.gov as #NCT02013167
Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab
Background: Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods: A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results: A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions: These data suggest that long-term survival is possible after blinatumomab therapy. Lay Summary: Immuno-oncology therapies such as blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with blinatumomab
Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation
Patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic stem cell transplantation (alloHSCT) have a poor prognosis, and alternative therapies are needed for this patient population. Blinatumomab, a bispecific T cell engager immunotherapy, was evaluated in an open-label, single-arm, phase II study of adults with R/R Philadelphia chromosome-negative B cell precursor ALL and resulted in a rate of complete remission (CR) or CR with partial hematologic recovery of peripheral blood counts (CRh) of 43% within 2 treatment cycles. We conducted an exploratory analysis to determine the efficacy and safety of blinatumomab in 64 patients who had relapsed following alloHSCT before enrollment in the phase II study. Forty-five percent of the patients (29 of 64) achieved a CR/CRh within the first 2 cycles of treatment, 22 of whom had a minimal residual disease (MRD) response (including 19 with a complete MRD response). After 1 year and 3 years of follow-up, the median relapse-free survival was 7.4 months for patients who achieved CR/CRh in the first 2 cycles, and the median overall survival was 8.5 months; overall survival rate (Kaplan-Meier estimate) was 36% at 1 year and 18% at 3 years. Grade 3 and 4 adverse events were reported in 20 patients (31%) and 28 patients (44%), respectively, with grade 3 and 4 neurologic events in 8 and 2 patients, respectively, and grade 3 cytokine release syndrome in 2 patients. Eight patients had fatal adverse events, including 5 due to infections. Seven patients had grade 64 3 graft-versus-host disease during the study, none of which resulted in the discontinuation of blinatumomab or hospitalization. Our data suggest that blinatumomab is an effective salvage therapy in this patient population
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Model-independent search for CP violation in D0âKâK+ÏâÏ+ and D0âÏâÏ+Ï+Ïâ decays
A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states KâK+ÏâÏ+ and ÏâÏ+Ï+Ïâ is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fbâ1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the KâK+ÏâÏ+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the ÏâÏ+Ï+Ïâ final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Search for the lepton-flavor-violating decays Bs0âe±Όâ and B0âe±Όâ
A search for the lepton-flavor-violating decays Bs0âe±Όâ and B0âe±Όâ is performed with a data sample, corresponding to an integrated luminosity of 1.0ââfb-1 of pp collisions at âs=7ââTeV, collected by the LHCb experiment. The observed number of Bs0âe±Όâ and B0âe±Όâ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0âe±Όâ)101ââTeV/c2 and MLQ(B0âe±Όâ)>126ââTeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) and the direct CP asymmetry in B0 -> K*0 gamma
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 phi gamma has been measured using an integrated luminosity of 1.0 fb-1
of pp collision data collected by the LHCb experiment at a centre-of-mass
energy of sqrt(s)=7 TeV. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 ->
phi gamma) = 1.23 +/- 0.06(stat.) +/- 0.04(syst.) +/- 0.10(fs/fd), where the
first uncertainty is statistical, the second is the experimental systematic
uncertainty and the third is associated with the ratio of fragmentation
fractions fs/fd. Using the world average value for BR(B0 -> K*0 gamma), the
branching fraction BR(Bs0 -> phi gamma) is measured to be (3.5 +/- 0.4) x
10^{-5}.
The direct CP asymmetry in B0 -> K*0 gamma decays has also been measured with
the same data and found to be A(CP)(B0 -> K*0 gamma) = (0.8 +/- 1.7(stat.) +/-
0.9(syst.))%.
Both measurements are the most precise to date and are in agreement with the
previous experimental results and theoretical expectations.Comment: 21 pages, 3 figues, 4 table
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
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