Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma ...(RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (
< 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (
< 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.
The marine diatom
Thalassiosira pseudonana
grown under air (0.04% CO
2
) and 1 and 5% CO
2
concentrations was evaluated to determine its potential for CO
2
mitigation coupled with biodiesel ...production. Results indicated that the diatom cultures grown at 1 and 5% CO
2
showed higher growth rates (1.14 and 1.29 div day
−1
, respectively) and biomass productivities (44 and 48 mg
AFDW
L
−1
day
−1
) than air grown cultures (with 1.13 div day
−1
and 26 mg
AFDW
L
−1
day
−1
). The increase of CO
2
resulted in higher cell volume and pigment content per cell of
T
.
pseudonana
. Interestingly, lipid content doubled when air was enriched with 1–5% CO
2
. Moreover, the analysis of the fatty acid composition of
T
.
pseudonana
revealed the predominance of monounsaturated acids (palmitoleic-16:1 and oleic-18:1) and a decrease of the saturated myristic acid-14:0 and polyunsaturated fatty acids under high CO
2
levels. These results suggested that
T
.
pseudonana
seems to be an ideal candidate for biodiesel production using flue gases.
The marine diatom Thalassiosira pseudonana grown under air (0.04% CO.sub.2) and 1 and 5% CO.sub.2 concentrations was evaluated to determine its potential for CO.sub.2 mitigation coupled with ...biodiesel production. Results indicated that the diatom cultures grown at 1 and 5% CO.sub.2 showed higher growth rates (1.14 and 1.29 div day.sup.-1, respectively) and biomass productivities (44 and 48 mg.sub.AFDWL.sup.-1 day.sup.-1) than air grown cultures (with 1.13 div day.sup.-1 and 26 mg.sub.AFDWL.sup.-1 day.sup.-1). The increase of CO.sub.2 resulted in higher cell volume and pigment content per cell of T. pseudonana. Interestingly, lipid content doubled when air was enriched with 1-5% CO.sub.2. Moreover, the analysis of the fatty acid composition of T. pseudonana revealed the predominance of monounsaturated acids (palmitoleic-16:1 and oleic-18:1) and a decrease of the saturated myristic acid-14:0 and polyunsaturated fatty acids under high CO.sub.2 levels. These results suggested that T. pseudonana seems to be an ideal candidate for biodiesel production using flue gases.
In this randomized phase 2 study (GEM-KyCyDex), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone was compared to carfilzomib and dexamethasone (Kd) in ...relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PLs). 197 patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PLs was 1 (1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, ≈70% to immunomodulators, and ≈50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomiderefractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 vs. 11.3 months (Hazard ratio 1.7 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PLs, but a significant benefit in PFS was observed with the triplet in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.
Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the ...massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs;
< 1 × 10
) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci,
,
,
,
,
, and
associated with MM risk (
= 4.47 × 10
-5.79 × 10
). Mechanistically, we found that the
SNP correlated with circulating concentrations of vitamin D3 (
= 4.0 × 10
), whereas the
SNP correlated with the number of transitional CD24
CD38
B cells (
= 4.8 × 10
) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (
= 3.6 × 10
). We also found that the
SNP correlated with numbers of CD19
B cells, CD19
CD3
B cells, CD5
IgD
cells, IgM
cells, IgD
IgM
cells, and CD4
CD8
PBMCs (
= 4.9 × 10
-8.6 × 10
) and circulating concentrations of interleukin (IL)-20 (
= 0.00082). Finally, we observed that the
SNP correlated with levels of CD4
EMCD45RO
CD27
cells (
= 9.3 × 10
). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3
, MCP-2
, and IL20-dependent pathways.
The marine diatom Thalassiosira pseudonana grown under air (0.04% CO
) and 1 and 5% CO
concentrations was evaluated to determine its potential for CO
mitigation coupled with biodiesel production. ...Results indicated that the diatom cultures grown at 1 and 5% CO
showed higher growth rates (1.14 and 1.29 div day
, respectively) and biomass productivities (44 and 48 mg
L
day
) than air grown cultures (with 1.13 div day
and 26 mg
L
day
). The increase of CO
resulted in higher cell volume and pigment content per cell of T. pseudonana. Interestingly, lipid content doubled when air was enriched with 1-5% CO
. Moreover, the analysis of the fatty acid composition of T. pseudonana revealed the predominance of monounsaturated acids (palmitoleic-16:1 and oleic-18:1) and a decrease of the saturated myristic acid-14:0 and polyunsaturated fatty acids under high CO
levels. These results suggested that T. pseudonana seems to be an ideal candidate for biodiesel production using flue gases.
Lo que se pretende con este artículo es dar luz las características diferenciales en el consumo de sustancias adictivas, teniendo en cuenta el género, con el objeto de poder brindar las herramientas ...e instrumentos esenciales que permitan el diseño de programas y tratamientos que incorporen dicha perspectiva en su práctica cotidiana. El objetivo es que los tratamientos sean de una mayor eficacia, tanto en el acceso/incorporación a éstos de las mujeres con adicciones, como en los resultados del proceso de rehabilitación. Las diferencias socialmente asignadas a cada uno de los sexos producen desigualdades que repercuten en un menoscabo en la salud, desarrollo y bienestar de las mujeres respecto a los hombres. Esta diferenciación social de género afectará en la necesaria adaptación de los programas y tratamientos para los distintos colectivos. A través de una metodología cualitativa (entrevistas en profundidad y focus group), se ha podido evidenciar –a partir del análisis de discurso–, cómo consumen las mujeres, a qué tipo de sustancias se las asocia más, las cargas sociales que se suman por ser mujer (múltiple discriminación) y las dificultades que ellas mismas muestran a la hora de acceder a un tratamiento de desintoxicación.
The intention with this article is to shed light on the different characteristics in the consumption of addictive substances considering gender, in order to provide the tools and instruments which are essential to the design of programs and treatments that incorporate that perspective in their daily practice. The final aim is that these treatments are of greater efficiency, both in access/joining these women with addictions, and the outcome of rehabilitation. It is, thus, to acquire more knowledge to better use of resources and services that are operated reintegration of addicts both private and public partnerships.
Differences socially assigned to each gender inequalities produced an impairment affecting the health, development and welfare of women relative to men. Through qualitative methods (interviews and focus groups), it has been evident from the analysis of discourse, how women consume, what kind of substances are more associations, social charges in addition to being a woman addicted (multiple discrimination) and difficulties show themselves when accessing drug treatment.
The intention with this article is to shed light on the different characteristics in the consumption of addictive substances considering gender, in order to provide the tools and instruments which ...are essential to the design of programs and treatments that incorporate that perspective in their daily practice. The final aim is that these treatments are of greater efficiency, both in access/joining these women with addictions, and the outcome of rehabilitation. It is, thus, to acquire more knowledge to better use of resources and services that are operated reintegration of addicts both private and public partnerships. Differences socially assigned to each gender inequalities produced an impairment affecting the health, development and welfare of women relative to men. Through qualitative methods (interviews and focus groups), it has been evident from the analysis of discourse, how women consume, what kind of substances are more associations, social charges in addition to being a woman addicted (multiple discrimination) and difficulties show themselves when accessing drug treatment. Adapted from the source document.
INTRODUCTION
Daratumumab is an anti-CD38 monoclonal antibody which is a recent success in the treatment of multiple myeloma (MM). It binds to the CD38 protein, which is highly expressed in MM tumor ...cells.
It is indicated in monotherapy in patients with relapsed MM, being refractory to treatment and having previously received a proteasome inhibitor and an immunomodulatory agent, with progression of the disease since the last treatment.
It can also be used, as stated recently in its data sheet, in combination with Lenalidomide and Dexamethasone or Bortezomib and Dexamethasone for the treatment of patients with MM who have received at least one previous treatment. It is being tested in combination with other drugs, which shows its enormous potential.
OBJECTIVES
We expose the experience with this drug in our center in recent years.
MATERIALS AND METHODS
We have evaluated patients treated with Daratumumab, recording: demographic data, previous number of lines of treatment, use in monotherapy or combination, date of initiation of treatment, response to it, date of suspension (if it occurred) and its cause, as well as total duration of the treatment (figure 1 and 2).
RESULTS
We studied 12 patients, 6 men and 6 women, treated with Daratumumab between 2016 and 2018. The average age is 63.75 years (range between 57 and 72).
On average, it was used in the 4th line of treatment, ranging between 2 cases in which it was the 2nd and 1 in which it was the 7th. In all patients, it was used in monotherapy.
Currently, 3 out of the 12 patients are still being treated with Daratumumab and they are in remission (objectified by PET-CT in 1 patient with only 4 months of treatment). 2 other patients are in partial remission (with 23 and 4 completed months of treatment, respectively). It was necessary to suspend the drug in 8 patients, in 7 cases due to progression of the disease. The remaining patient suffered, in the 1st administration, an adverse reaction of type III that was refractory to the symptomatic treatment and to the decrease of the infusion rate, which forced to withdraw the drug.
In 4 cases, the drug was discontinued and the result was “stable disease”, so it remained until progression was evidenced. The average maintenance of the drug until progression was 4 months, ranging between 2 and 6 months. In the remaining 3 patients the disease progressed, so the drug was discontinued.
CONCLUSIONS
The MM treatment has to be individualized and adapted to the risks. The data obtained from our patients indicate that Daratumumab is a potentially valuable drug among the therapeutic arsenal against this pathology. However, we believe that the results would be much better if the treatment is started in earlier lines.
Rios:Amgen, Celgene, Janssen, and Takeda: Consultancy.
Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the
and
loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study ...including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the
genotype had a significantly increased risk of developing IA (
= 0.00022). We also found that carriers of the
allele showed decreased serum levels of TNFSF14 protein (
= 0.0027), and that their macrophages had a decreased fungicidal activity (
= 0.048). In addition, we observed that each copy of the
allele increased the risk of IA by 60% (
= 0.0017), whereas each copy of the
allele was estimated to decrease the risk of developing the disease (
= 0.0029). Mechanistically, we found that carriers of the risk
allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (
= 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (
= 0.00097). Finally, we also found that carriers of the protective
allele had decreased numbers of CD27-IgM-IgD- B cells (
= 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (
= 0.00018 and 0.00023). Altogether, these results suggest a role of the
genes in determining IA risk.
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