Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Abstract

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(−) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(−) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

http://ift.tt/2genv6u

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS)

Abstract

Introduction

An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here.

Methods

Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity.

Results

Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids.

Conclusions

These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients.

Funding

Molteni Farmaceutici, Italy.

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Association of Performance Status and Pain in Metastatic Bone Pain Management in the Spanish Clinical Setting

Abstract

Introduction

Bone metastasis is the most common cause of cancer-related pain, and metastatic bone pain (MBP) is not only severe but also progressive in many patients. The aim of this study was to investigate the association between pain management and performance status in patients with metastatic bone cancer in the Spanish clinical setting.

Methods

A 3-month follow-up prospective, epidemiologic, multicenter study was conducted in 579 patients to assess the evolution of their performance, the impact of pain control on sleep and functionality, and the degree of pain control according to analgesic treatment.

Results

In patients with MBP, Eastern Cooperative Oncology Group (ECOG) status (1.5 ± 0.7–1.3 ± 0.7 and 1.3 ± 0.8; p < 0.001) and pain (6.5 ± 1.4–2.8 ± 1.9 and 2.1 ± 1.9; p < 0.001) improved significantly from baseline to months 1 and 3, as did functionality and sleep, after a treatment change consisting of increasing the administration of opioids. Evolution of ECOG and pain were closely related. ECOG and pain outcomes were significantly more favorable in patients treated with opioids versus non-opioid treatment, and in patients who did not need rescue medication versus those who did.

Conclusions

MBP is currently poorly managed in Spain. ECOG improvement is closely and directly related to pain management in MBP. Opioid treatment and a lack of requirements for rescue medication are associated with better ECOG and pain outcomes in MBP patients.

Funding

Mundipharma Pharmaceuticals S.L.

from Cancer via ola Kala on Inoreader http://ift.tt/2floT87
via IFTTT

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Abstract

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(−) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(−) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

from Cancer via ola Kala on Inoreader http://ift.tt/2genv6u
via IFTTT

Newly designed retentive posts of mandibular reconstruction plate in oral cancer patients based on preliminary FEM study

Abstract

Background

The reconstruction of a large mandibular defect poses a challenging issue in oral cancer ablation surgery. One popular option for mandibular continuity reconstruction after tumor resection involves the use of a reconstruction plate (R-plate), which maintains space and contour without bone harvesting. An R-plate, however, cannot provide final functional loading rehabilitation with implants or dentures.

Methods

We suggest a new method of functional mandibular reconstruction using retentive posts and an upper prosthesis. The finite element method (FEM) was used to optimize the design. Surgery was needed to adapt the retentive posts. Prosthodontic procedures were required for the upper prosthesis.

Results

Eight patients were treated with retentive posts and prostheses. All patients underwent wide resections of the mandible, and reconstruction with an R-plate and microvascular soft tissue transfer. We adapted the retentive posts on an R-plate and fabricated the upper prostheses with a flexible denture or a fixed resin prosthesis. Finally, the patients had functional rehabilitation, which restored proper mastication.

Conclusions

The retentive posts of the R-plate and upper prosthesis allow functional dental rehabilitation without the need for a bone graft. Virtual simulation using FEM will help to design and optimize the retentive posts. Two or three regular size posts are suitable for the quadrant jaw. This first preliminary step will allow improved patient-specific retentive post designs in the near future.

from Cancer via ola Kala on Inoreader http://ift.tt/2gvQWDG
via IFTTT

Newly designed retentive posts of mandibular reconstruction plate in oral cancer patients based on preliminary FEM study

Abstract

Background

The reconstruction of a large mandibular defect poses a challenging issue in oral cancer ablation surgery. One popular option for mandibular continuity reconstruction after tumor resection involves the use of a reconstruction plate (R-plate), which maintains space and contour without bone harvesting. An R-plate, however, cannot provide final functional loading rehabilitation with implants or dentures.

Methods

We suggest a new method of functional mandibular reconstruction using retentive posts and an upper prosthesis. The finite element method (FEM) was used to optimize the design. Surgery was needed to adapt the retentive posts. Prosthodontic procedures were required for the upper prosthesis.

Results

Eight patients were treated with retentive posts and prostheses. All patients underwent wide resections of the mandible, and reconstruction with an R-plate and microvascular soft tissue transfer. We adapted the retentive posts on an R-plate and fabricated the upper prostheses with a flexible denture or a fixed resin prosthesis. Finally, the patients had functional rehabilitation, which restored proper mastication.

Conclusions

The retentive posts of the R-plate and upper prosthesis allow functional dental rehabilitation without the need for a bone graft. Virtual simulation using FEM will help to design and optimize the retentive posts. Two or three regular size posts are suitable for the quadrant jaw. This first preliminary step will allow improved patient-specific retentive post designs in the near future.

http://ift.tt/2gvQWDG

Severe changes in colon epithelium in the Mecp2 -null mouse model of Rett syndrome

Abstract

Background

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice.

Methods

Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples.

Results

First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice.

Conclusions

In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

http://ift.tt/2fiIItF