Histopathology is considered the gold standard diagnostic method for canine mammary tumors. In 2011, a new histologic classification for canine mammary tumors was proposed. The present study was a ...2-year prospective study that validated the 2011 classification as an independent prognostic indicator with multivariate analysis in a population of 229 female dogs, identifying subtype-specific median survival times (MST) and local recurrence/distant metastasis rates. Dogs with benign tumors and carcinoma arising in benign mixed tumors all had an excellent prognosis. Dogs with complex carcinoma and simple tubular carcinoma also experienced prolonged survival. Those with simple tubulopapillary carcinoma, intraductal papillary carcinoma, and carcinoma and malignant myoepithelioma had a more than 10-fold higher risk of tumor-related death. The prognosis was even worse for adenosquamous carcinoma (MST = 18 months), comedocarcinoma (MST = 14 months), and solid carcinoma (MST = 8 months). The most unfavorable outcome was for anaplastic carcinoma (MST = 3 months) and carcinosarcoma (MST = 3 months), which also had the highest metastatic rates (89% and 100%, respectively). Adenosquamous carcinoma exhibited the highest local recurrence rate (50%). In the same canine population, the tumor diameter was recognized as a strong predictor of local recurrence/distant metastasis and an independent prognosticator of survival in the multivariate analysis. Excision margins were predictive only of local recurrence, whereas lymphatic invasion and histologic grade were predictive of local recurrence/distant metastasis and survival, although only in univariate analyses. In conclusion, this study validated the 2011 classification scheme and provided information to be used in the clinical setting and as the basis for future prognostic studies.
Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) -targeted drugs in patients with non-small-cell ...lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC.
Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was required to assess MET status by immunohistochemistry (IHC). Coprimary end points were progression-free survival (PFS) in the intent-to-treat (ITT) and MET-positive (MET IHC diagnostic positive) populations; additional end points included overall survival (OS), objective response rate, and safety.
There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard ratio HR, 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66) treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53; P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR, 1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzumab-treated patients.
Onartuzumab plus erlotinib was associated with improved PFS and OS in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development.
•This EHA-ESMO Clinical Practice Guideline provides key recommendations on the management of multiple myeloma.•Authorship includes a multidisciplinary group of experts from different institutions and ...countries in Europe.•Key treatment recommendations are provided for both newly diagnosed myeloma patients and patients with relapsed/refractory disease.•Recommendations for the treatment of plasma cell leukaemia, solitary plasmacytoma and smouldering myeloma are also provided.•Key recommendations for myeloma complications, including bone disease and renal impairment, are included.
Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether ...the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.
We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.
At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients 26.4% in the daratumumab group and 143 of 369 patients 38.8% in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval CI, 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10
white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).
Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).
Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed ...multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T
). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T
was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T
was 3.1 years. The median number of lines of therapy before T
was 4 (range 3-13). The median overall survival (OS) from T
for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T
in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T
of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated.
Weitere Zielgrößen sind das progressionsfreie Überleben (progression free survival, PFS) und Lebensqualität/Verträglichkeit. Dazu haben wir zum ASH 2018 Abstracts eingereicht und freuen uns, dass wir ...in einer großen Session gleich 2 Vorträge halten durften. Der Start der Studie war im Jahr 2016 (https://www.curetalks.com/event/rsvp/Understanding-iSTOPMM-Iceland-Screens-Treats-or-Prevents-Multiple-Myeloma-with-Dr-Sigurour-Yngvi-Kristinsson/257/). Diese Studie lieferte das Argument für den internationalen Einsatz der Kernspintomographie bei Frühformen des Multiplen Myeloms. best practice onkologie:
Multiple myeloma is characterized by underlying clinical and biological heterogeneity, which translates to variable response to treatment and outcome. With the recent increase in treatment ...armamentarium and the projected further increase in approved therapeutic agents in the coming years, the issue of having some mechanism to dissect this heterogeneity and rationally apply treatment is coming to the fore. A number of robustly validated prognostic markers have been identified and the use of these markers in stratifying patients into different risk groups has been proposed. In this consensus statement, the International Myeloma Working Group propose well-defined and easily applicable risk categories based on current available information and suggests the use of this set of prognostic factors as gold standards in all clinical trials and form the basis of subsequent development of more complex prognostic system or better prognostic factors. At the same time, these risk categories serve as a framework to rationalize the use of therapies.
One of the hallmarks of adaptive immunity is the development of a long-term pathogen specific memory response. While persistent memory T cells certainly impact the immune response during a secondary ...challenge, their role in unrelated infections is less clear. To address this issue, we utilized lymphocytic choriomeningitis virus (LCMV) and Listeria monocytogenes immune mice to investigate whether bystander memory T cells influence Leishmania major infection. Despite similar parasite burdens, LCMV and Listeria immune mice exhibited a significant increase in leishmanial lesion size compared to mice infected with L. major alone. This increased lesion size was due to a severe inflammatory response, consisting not only of monocytes and neutrophils, but also significantly more CD8 T cells. Many of the CD8 T cells were LCMV specific and expressed gzmB and NKG2D, but unexpectedly expressed very little IFN-γ. Moreover, if CD8 T cells were depleted in LCMV immune mice prior to challenge with L. major, the increase in lesion size was lost. Strikingly, treating with NKG2D blocking antibodies abrogated the increased immunopathology observed in LCMV immune mice, showing that NKG2D engagement on LCMV specific memory CD8 T cells was required for the observed phenotype. These results indicate that bystander memory CD8 T cells can participate in an unrelated immune response and induce immunopathology through an NKG2D dependent mechanism without providing increased protection.
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