SAN DIEGO – The number of lung volume–reduction surgeries performed in the United States has been increasing since 2011, according to a large national analysis.

Lung volume–reduction surgery (LVRS) has been available for decades, but results from the National Emphysema Treatment Trial (NETT) in 2003 (N Engl J Med 2003;348:2059-73) demonstrated that certain COPD patients benefited from the surgery, Amy Attaway, MD, said at an international conference of the American Thoracic Society.

In that trial, overall mortality at 30 days was 3.6% for the surgical group. “If you excluded high-risk patients, the 30-day mortality was only 2.2%,” said Dr. Attaway, a staff physician at the Cleveland Clinic Respiratory Institute. “If you look at the upper lobe–predominant, low-exercise group, their mortality at 30 days was 1.4%.”

Subsequent studies that evaluated NETT patients over time showed continued improvements in their mortality. For example, one study found that in the upper lobe–predominant patients who received surgery in the NETT trial, their survival at 3 years was 81% vs. 74% in the medical group (P = .05), while survival at 5 years was 70% in the surgery group vs. 60% in the medical group (P = .02; J Thorac Cardiovasc Surg. 2010;140[3]:564-72). Despite this improved mortality, other studies have shown that LVRS remains underutilized. Once such analysis of the Nationwide Inpatient Sample showed a logarithmic drop from 2000 to 2010 (Chest 2014;146[6]:e228-9). The authors also noted that the overall mortality was 6% and that the need for a tracheostomy was 7.9%. Age greater than 65 years was associated with increased mortality (odds ratio 2.8).

Dr. Attaway and her associates hypothesized that availability of the long-term survival data from the NETT, support from GOLD guidelines, and the lack of a Food and Drug Administration–approved alternative may have increased utilization of this surgery from 2007 through 2013. With data from the Nationwide Inpatient Sample for 2007-2013, the researchers performed a retrospective cohort analysis of 2,805 patients who underwent LVRS. The composite primary outcome was mortality or need for tracheostomy. Logistic regression was performed to analyze factors associated with the composite primary outcome.

The average patient age was 59 years, and 64% were male. Medicare was the payer in nearly half of cases, in-hospital mortality and need for tracheostomy were both 5.5%, and the risk for tracheostomy or mortality was 10.5%. Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).

On univariate analysis, the following factors were found to be significantly associated with the composite primary outcome: in-hospital mortality or the need for tracheostomy (P less than .001), respiratory failure (P less than .001), septicemia (P = .01), shock (P less than .001), acute kidney injury (P less than .001), secondary pulmonary hypertension (P less than .001), and a higher mean number of diagnoses or number of chronic conditions on admission (P less than .001 and P = .017, respectively).

On multivariate logistic regression, only two factors were found to be significantly associated with the composite primary outcome: a higher number of diagnoses (adjusted OR of 1.17 per additional diagnosis), and the presence of secondary pulmonary hypertension (adjusted OR 4.4).

“Availability of long-term survival data from NETT, support from the GOLD guidelines, and lack of current FDA-approved alternatives are potential reasons for increased utilization [of LVRS],” Dr. Attaway said. “However, our study showed that in-hospital mortality and morbidity is high, compared to the NETT results. We also found that secondary pulmonary hypertension and comorbidities are associated with poor outcomes. This is important to keep in mind for patient selection.”

Dr. Attaway and her associates reported having no financial disclosures.

[email protected]

SOURCE: Attaway A et al. ATS 2018, Abstract 4436.

SAN DIEGO – The number of lung volume–reduction surgeries performed in the United States has been increasing since 2011, according to a large national analysis.

Lung volume–reduction surgery (LVRS) has been available for decades, but results from the National Emphysema Treatment Trial (NETT) in 2003 (N Engl J Med 2003;348:2059-73) demonstrated that certain COPD patients benefited from the surgery, Amy Attaway, MD, said at an international conference of the American Thoracic Society.

In that trial, overall mortality at 30 days was 3.6% for the surgical group. “If you excluded high-risk patients, the 30-day mortality was only 2.2%,” said Dr. Attaway, a staff physician at the Cleveland Clinic Respiratory Institute. “If you look at the upper lobe–predominant, low-exercise group, their mortality at 30 days was 1.4%.”

Subsequent studies that evaluated NETT patients over time showed continued improvements in their mortality. For example, one study found that in the upper lobe–predominant patients who received surgery in the NETT trial, their survival at 3 years was 81% vs. 74% in the medical group (P = .05), while survival at 5 years was 70% in the surgery group vs. 60% in the medical group (P = .02; J Thorac Cardiovasc Surg. 2010;140[3]:564-72). Despite this improved mortality, other studies have shown that LVRS remains underutilized. Once such analysis of the Nationwide Inpatient Sample showed a logarithmic drop from 2000 to 2010 (Chest 2014;146[6]:e228-9). The authors also noted that the overall mortality was 6% and that the need for a tracheostomy was 7.9%. Age greater than 65 years was associated with increased mortality (odds ratio 2.8).

Dr. Attaway and her associates hypothesized that availability of the long-term survival data from the NETT, support from GOLD guidelines, and the lack of a Food and Drug Administration–approved alternative may have increased utilization of this surgery from 2007 through 2013. With data from the Nationwide Inpatient Sample for 2007-2013, the researchers performed a retrospective cohort analysis of 2,805 patients who underwent LVRS. The composite primary outcome was mortality or need for tracheostomy. Logistic regression was performed to analyze factors associated with the composite primary outcome.

The average patient age was 59 years, and 64% were male. Medicare was the payer in nearly half of cases, in-hospital mortality and need for tracheostomy were both 5.5%, and the risk for tracheostomy or mortality was 10.5%. Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).

On univariate analysis, the following factors were found to be significantly associated with the composite primary outcome: in-hospital mortality or the need for tracheostomy (P less than .001), respiratory failure (P less than .001), septicemia (P = .01), shock (P less than .001), acute kidney injury (P less than .001), secondary pulmonary hypertension (P less than .001), and a higher mean number of diagnoses or number of chronic conditions on admission (P less than .001 and P = .017, respectively).

On multivariate logistic regression, only two factors were found to be significantly associated with the composite primary outcome: a higher number of diagnoses (adjusted OR of 1.17 per additional diagnosis), and the presence of secondary pulmonary hypertension (adjusted OR 4.4).

“Availability of long-term survival data from NETT, support from the GOLD guidelines, and lack of current FDA-approved alternatives are potential reasons for increased utilization [of LVRS],” Dr. Attaway said. “However, our study showed that in-hospital mortality and morbidity is high, compared to the NETT results. We also found that secondary pulmonary hypertension and comorbidities are associated with poor outcomes. This is important to keep in mind for patient selection.”

Dr. Attaway and her associates reported having no financial disclosures.

[email protected]

SOURCE: Attaway A et al. ATS 2018, Abstract 4436.

SAN DIEGO – The number of lung volume–reduction surgeries performed in the United States has been increasing since 2011, according to a large national analysis.

Lung volume–reduction surgery (LVRS) has been available for decades, but results from the National Emphysema Treatment Trial (NETT) in 2003 (N Engl J Med 2003;348:2059-73) demonstrated that certain COPD patients benefited from the surgery, Amy Attaway, MD, said at an international conference of the American Thoracic Society.

In that trial, overall mortality at 30 days was 3.6% for the surgical group. “If you excluded high-risk patients, the 30-day mortality was only 2.2%,” said Dr. Attaway, a staff physician at the Cleveland Clinic Respiratory Institute. “If you look at the upper lobe–predominant, low-exercise group, their mortality at 30 days was 1.4%.”

Subsequent studies that evaluated NETT patients over time showed continued improvements in their mortality. For example, one study found that in the upper lobe–predominant patients who received surgery in the NETT trial, their survival at 3 years was 81% vs. 74% in the medical group (P = .05), while survival at 5 years was 70% in the surgery group vs. 60% in the medical group (P = .02; J Thorac Cardiovasc Surg. 2010;140[3]:564-72). Despite this improved mortality, other studies have shown that LVRS remains underutilized. Once such analysis of the Nationwide Inpatient Sample showed a logarithmic drop from 2000 to 2010 (Chest 2014;146[6]:e228-9). The authors also noted that the overall mortality was 6% and that the need for a tracheostomy was 7.9%. Age greater than 65 years was associated with increased mortality (odds ratio 2.8).

Dr. Attaway and her associates hypothesized that availability of the long-term survival data from the NETT, support from GOLD guidelines, and the lack of a Food and Drug Administration–approved alternative may have increased utilization of this surgery from 2007 through 2013. With data from the Nationwide Inpatient Sample for 2007-2013, the researchers performed a retrospective cohort analysis of 2,805 patients who underwent LVRS. The composite primary outcome was mortality or need for tracheostomy. Logistic regression was performed to analyze factors associated with the composite primary outcome.

The average patient age was 59 years, and 64% were male. Medicare was the payer in nearly half of cases, in-hospital mortality and need for tracheostomy were both 5.5%, and the risk for tracheostomy or mortality was 10.5%. Linear regression analysis showed a significant increase in LVRS over time, with the 320 surgeries in 2007 and 605 in 2013 (P = .0016).

On univariate analysis, the following factors were found to be significantly associated with the composite primary outcome: in-hospital mortality or the need for tracheostomy (P less than .001), respiratory failure (P less than .001), septicemia (P = .01), shock (P less than .001), acute kidney injury (P less than .001), secondary pulmonary hypertension (P less than .001), and a higher mean number of diagnoses or number of chronic conditions on admission (P less than .001 and P = .017, respectively).

On multivariate logistic regression, only two factors were found to be significantly associated with the composite primary outcome: a higher number of diagnoses (adjusted OR of 1.17 per additional diagnosis), and the presence of secondary pulmonary hypertension (adjusted OR 4.4).

“Availability of long-term survival data from NETT, support from the GOLD guidelines, and lack of current FDA-approved alternatives are potential reasons for increased utilization [of LVRS],” Dr. Attaway said. “However, our study showed that in-hospital mortality and morbidity is high, compared to the NETT results. We also found that secondary pulmonary hypertension and comorbidities are associated with poor outcomes. This is important to keep in mind for patient selection.”

Dr. Attaway and her associates reported having no financial disclosures.

[email protected]

SOURCE: Attaway A et al. ATS 2018, Abstract 4436.

Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.

In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.

The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.

The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.

Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).

Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.

About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.

“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”

The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.

The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.

SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.

Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.

In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.

The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.

The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.

Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).

Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.

About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.

“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”

The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.

The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.

SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.

Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.

In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.

The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.

The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.

Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).

Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.

About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.

“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”

The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.

The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.

SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.

Steatocystoma multiplex is an uncommon inherited condition in which multiple lesions are formed, most commonly appearing on the trunk, axillae, and groin. Different types of steatocystoma multiplex have been described: localized, generalized, facial, acral, and suppurative (in which the lesions resemble hidradenitis suppurativa).

This condition is autosomal dominant and is linked to defects in KRT17 gene, which instructs the production of keratin 17. However, some cases of steatocystoma multiplex occur sporadically with no mutation in the KRT17 gene; in them, the cause is unknown. Steatocystoma multiplex may be associated with eruptive vellus hair cysts and pachyonychia congenita (nail and teeth abnormalities and palmoplantar keratoderma). Lesions often appear during adolescence, when an individual hits puberty. Hormones likely influence the development of the cysts from the pilosebaceous unit. If there is a single steatocystoma, it is called steatocystoma simplex.

Steatocystomas do not resolve on their own. The small, benign cysts are located fairly superficial in the dermis. If punctured, they drain a yellow, oily liquid sebum. Lesions may become inflamed and may heal with scarring, as in acne. They may be treated by incision and drainage or excision to remove the cyst wall. Electrosurgery and cryotherapy may be used. Oral antibiotics may improve inflamed lesions. There are reports in the literature in which isotretinoin has helped; however, it is not curative. In some cases, the lesions can reoccur and may even be worse.
 

Case and photo submitted by: Donna Bilu Martin, MD; Premier Dermatology, MD; Aventura, Fla.

Steatocystoma multiplex is an uncommon inherited condition in which multiple lesions are formed, most commonly appearing on the trunk, axillae, and groin. Different types of steatocystoma multiplex have been described: localized, generalized, facial, acral, and suppurative (in which the lesions resemble hidradenitis suppurativa).

This condition is autosomal dominant and is linked to defects in KRT17 gene, which instructs the production of keratin 17. However, some cases of steatocystoma multiplex occur sporadically with no mutation in the KRT17 gene; in them, the cause is unknown. Steatocystoma multiplex may be associated with eruptive vellus hair cysts and pachyonychia congenita (nail and teeth abnormalities and palmoplantar keratoderma). Lesions often appear during adolescence, when an individual hits puberty. Hormones likely influence the development of the cysts from the pilosebaceous unit. If there is a single steatocystoma, it is called steatocystoma simplex.

Steatocystomas do not resolve on their own. The small, benign cysts are located fairly superficial in the dermis. If punctured, they drain a yellow, oily liquid sebum. Lesions may become inflamed and may heal with scarring, as in acne. They may be treated by incision and drainage or excision to remove the cyst wall. Electrosurgery and cryotherapy may be used. Oral antibiotics may improve inflamed lesions. There are reports in the literature in which isotretinoin has helped; however, it is not curative. In some cases, the lesions can reoccur and may even be worse.
 

Case and photo submitted by: Donna Bilu Martin, MD; Premier Dermatology, MD; Aventura, Fla.

Steatocystoma multiplex is an uncommon inherited condition in which multiple lesions are formed, most commonly appearing on the trunk, axillae, and groin. Different types of steatocystoma multiplex have been described: localized, generalized, facial, acral, and suppurative (in which the lesions resemble hidradenitis suppurativa).

This condition is autosomal dominant and is linked to defects in KRT17 gene, which instructs the production of keratin 17. However, some cases of steatocystoma multiplex occur sporadically with no mutation in the KRT17 gene; in them, the cause is unknown. Steatocystoma multiplex may be associated with eruptive vellus hair cysts and pachyonychia congenita (nail and teeth abnormalities and palmoplantar keratoderma). Lesions often appear during adolescence, when an individual hits puberty. Hormones likely influence the development of the cysts from the pilosebaceous unit. If there is a single steatocystoma, it is called steatocystoma simplex.

Steatocystomas do not resolve on their own. The small, benign cysts are located fairly superficial in the dermis. If punctured, they drain a yellow, oily liquid sebum. Lesions may become inflamed and may heal with scarring, as in acne. They may be treated by incision and drainage or excision to remove the cyst wall. Electrosurgery and cryotherapy may be used. Oral antibiotics may improve inflamed lesions. There are reports in the literature in which isotretinoin has helped; however, it is not curative. In some cases, the lesions can reoccur and may even be worse.
 

Case and photo submitted by: Donna Bilu Martin, MD; Premier Dermatology, MD; Aventura, Fla.

“Before you are a leader, success is all about growing yourself. When you become a leader, success is all about growing others.” – Jack Welch

Serving my colleagues as chairman of the department of hematology and medical oncology at the Cleveland Clinic has been my greatest honor and privilege. I am humbled to lead such compassionate, inquisitive, and accomplished clinician scientists during a time of great change in academic medicine. From the introduction of new therapies to the implementation of new operational processes, my team inspires me to extend my capability beyond what I ever thought possible. I am grateful for the opportunity to grow with them.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

“Before you are a leader, success is all about growing yourself. When you become a leader, success is all about growing others.” – Jack Welch

Serving my colleagues as chairman of the department of hematology and medical oncology at the Cleveland Clinic has been my greatest honor and privilege. I am humbled to lead such compassionate, inquisitive, and accomplished clinician scientists during a time of great change in academic medicine. From the introduction of new therapies to the implementation of new operational processes, my team inspires me to extend my capability beyond what I ever thought possible. I am grateful for the opportunity to grow with them.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

“Before you are a leader, success is all about growing yourself. When you become a leader, success is all about growing others.” – Jack Welch

Serving my colleagues as chairman of the department of hematology and medical oncology at the Cleveland Clinic has been my greatest honor and privilege. I am humbled to lead such compassionate, inquisitive, and accomplished clinician scientists during a time of great change in academic medicine. From the introduction of new therapies to the implementation of new operational processes, my team inspires me to extend my capability beyond what I ever thought possible. I am grateful for the opportunity to grow with them.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

Platinum-based chemotherapy is effective in metastatic triple negative breast cancer (mTNBC), but predictive biomarkers would help identify the best candidates for the treatment. Two sets of parameters—neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)—have already demonstrated their prognostic prowess in many malignancies, but how well will they do in platinum-treated mTNBC patients? Researchers from Fondazione IRCCS Istituto Nazionale dei Tumori, in Milan, Italy conducted a retrospective, single-center study to evaluate the association between baseline NLR or PLR and progression-free survival (PFS) in 57 mTNBC patients treated with carboplatin-paclitaxel or carboplatin-gemcitabine between 2007 and 2017, compared with 148 patients with hormone receptor-positive HER2-negative metastatic breast cancer.

Response was assessed every 3 chemotherapy cycles. Among platinum-treated patients, high NLR and PLR were associated with significantly lower PFS. Median PFS was 304 days in patients with NLR < 2.5, and 158 days in those with NLR ≥ 2.5. Progression-free survival was longer in patients with baseline PLR < 200, compared with PLR ≥ 200. The researchers found no significant association between NLR or PLR and the PFS of control patients.

When the same parameters were evaluated before the administration of the third treatment cycle, NLR < 2.5 was still associated with reduced risk of disease progression, although PLR < 200 was not.

In patients with mTNBC, median overall survival was significantly longer in patients with NLR < 2.5 compared with NLR ≥ 2.5. Platelet-to-lymphocyte ratio values were not associated with overall survival. The ratios also appeared to have a generally prognostic role independently from tumor biology.

The hormone receptors for NLR and PLR in multivariable analysis for PFS were similar, and the parameters correlated with each other, the researchers say, suggesting that both NLR and PLR “well reflect the inflammatory/immune contexture in mTNBC, and may be redundant as predictive biomarkers.”

Source:
Vernieri C, Mennitto A, Prisciandaro M, et al. Sci Rep. 2018;8(1):8703.

Platinum-based chemotherapy is effective in metastatic triple negative breast cancer (mTNBC), but predictive biomarkers would help identify the best candidates for the treatment. Two sets of parameters—neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)—have already demonstrated their prognostic prowess in many malignancies, but how well will they do in platinum-treated mTNBC patients? Researchers from Fondazione IRCCS Istituto Nazionale dei Tumori, in Milan, Italy conducted a retrospective, single-center study to evaluate the association between baseline NLR or PLR and progression-free survival (PFS) in 57 mTNBC patients treated with carboplatin-paclitaxel or carboplatin-gemcitabine between 2007 and 2017, compared with 148 patients with hormone receptor-positive HER2-negative metastatic breast cancer.

Response was assessed every 3 chemotherapy cycles. Among platinum-treated patients, high NLR and PLR were associated with significantly lower PFS. Median PFS was 304 days in patients with NLR < 2.5, and 158 days in those with NLR ≥ 2.5. Progression-free survival was longer in patients with baseline PLR < 200, compared with PLR ≥ 200. The researchers found no significant association between NLR or PLR and the PFS of control patients.

When the same parameters were evaluated before the administration of the third treatment cycle, NLR < 2.5 was still associated with reduced risk of disease progression, although PLR < 200 was not.

In patients with mTNBC, median overall survival was significantly longer in patients with NLR < 2.5 compared with NLR ≥ 2.5. Platelet-to-lymphocyte ratio values were not associated with overall survival. The ratios also appeared to have a generally prognostic role independently from tumor biology.

The hormone receptors for NLR and PLR in multivariable analysis for PFS were similar, and the parameters correlated with each other, the researchers say, suggesting that both NLR and PLR “well reflect the inflammatory/immune contexture in mTNBC, and may be redundant as predictive biomarkers.”

Source:
Vernieri C, Mennitto A, Prisciandaro M, et al. Sci Rep. 2018;8(1):8703.

Platinum-based chemotherapy is effective in metastatic triple negative breast cancer (mTNBC), but predictive biomarkers would help identify the best candidates for the treatment. Two sets of parameters—neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)—have already demonstrated their prognostic prowess in many malignancies, but how well will they do in platinum-treated mTNBC patients? Researchers from Fondazione IRCCS Istituto Nazionale dei Tumori, in Milan, Italy conducted a retrospective, single-center study to evaluate the association between baseline NLR or PLR and progression-free survival (PFS) in 57 mTNBC patients treated with carboplatin-paclitaxel or carboplatin-gemcitabine between 2007 and 2017, compared with 148 patients with hormone receptor-positive HER2-negative metastatic breast cancer.

Response was assessed every 3 chemotherapy cycles. Among platinum-treated patients, high NLR and PLR were associated with significantly lower PFS. Median PFS was 304 days in patients with NLR < 2.5, and 158 days in those with NLR ≥ 2.5. Progression-free survival was longer in patients with baseline PLR < 200, compared with PLR ≥ 200. The researchers found no significant association between NLR or PLR and the PFS of control patients.

When the same parameters were evaluated before the administration of the third treatment cycle, NLR < 2.5 was still associated with reduced risk of disease progression, although PLR < 200 was not.

In patients with mTNBC, median overall survival was significantly longer in patients with NLR < 2.5 compared with NLR ≥ 2.5. Platelet-to-lymphocyte ratio values were not associated with overall survival. The ratios also appeared to have a generally prognostic role independently from tumor biology.

The hormone receptors for NLR and PLR in multivariable analysis for PFS were similar, and the parameters correlated with each other, the researchers say, suggesting that both NLR and PLR “well reflect the inflammatory/immune contexture in mTNBC, and may be redundant as predictive biomarkers.”

Source:
Vernieri C, Mennitto A, Prisciandaro M, et al. Sci Rep. 2018;8(1):8703.

Flavorings used in e-cigarettes have a negative impact on endothelial cells that may play a role in cardiovascular toxicity.

Flavored tobacco products are popular among current smokers, including youth, and the flavorings have been deemed ingestible, but their impact on heart health has not been studied, wrote Jennifer Fetterman, PhD, of Boston University, and her colleagues. The report was published in Arteriosclerosis, Thrombosis, and Vascular Biology.

The researchers studied nine types of flavorings used in alternative tobacco products to assess their impact on cardiovascular health.

The first part of the study comprised a population of nine nonsmokers, six nonmenthol cigarette smokers, and six menthol cigarette smokers without cardiovascular disease. The researchers isolated venous endothelial cells from each participant.

Overall, cells from both nonmenthol and menthol cigarette smokers had significantly lower nitric oxide production compared with nonsmokers (P = .003 and P = .012, respectively). In addition, the flavoring compounds menthol and eugenol impaired nitric oxide production in the cells of healthy individuals.

“Increased inflammation and a loss of nitric oxide are some of the first changes to occur leading up to cardiovascular disease and events like heart attacks and stroke, so they are considered early predictors of heart disease,” Dr. Fetterman said in a statement, adding that the “findings suggest that these flavoring additives may have serious health consequences.”

Carpe89/ThinkStock

SOURCE: Fetterman J et al. Arterioscler Thromb Vasc Biol. 2018. doi: 10.1161/ATVBAHA.118.311156.

Flavorings used in e-cigarettes have a negative impact on endothelial cells that may play a role in cardiovascular toxicity.

Flavored tobacco products are popular among current smokers, including youth, and the flavorings have been deemed ingestible, but their impact on heart health has not been studied, wrote Jennifer Fetterman, PhD, of Boston University, and her colleagues. The report was published in Arteriosclerosis, Thrombosis, and Vascular Biology.

The researchers studied nine types of flavorings used in alternative tobacco products to assess their impact on cardiovascular health.

The first part of the study comprised a population of nine nonsmokers, six nonmenthol cigarette smokers, and six menthol cigarette smokers without cardiovascular disease. The researchers isolated venous endothelial cells from each participant.

Overall, cells from both nonmenthol and menthol cigarette smokers had significantly lower nitric oxide production compared with nonsmokers (P = .003 and P = .012, respectively). In addition, the flavoring compounds menthol and eugenol impaired nitric oxide production in the cells of healthy individuals.

“Increased inflammation and a loss of nitric oxide are some of the first changes to occur leading up to cardiovascular disease and events like heart attacks and stroke, so they are considered early predictors of heart disease,” Dr. Fetterman said in a statement, adding that the “findings suggest that these flavoring additives may have serious health consequences.”

Carpe89/ThinkStock

SOURCE: Fetterman J et al. Arterioscler Thromb Vasc Biol. 2018. doi: 10.1161/ATVBAHA.118.311156.

Flavorings used in e-cigarettes have a negative impact on endothelial cells that may play a role in cardiovascular toxicity.

Flavored tobacco products are popular among current smokers, including youth, and the flavorings have been deemed ingestible, but their impact on heart health has not been studied, wrote Jennifer Fetterman, PhD, of Boston University, and her colleagues. The report was published in Arteriosclerosis, Thrombosis, and Vascular Biology.

The researchers studied nine types of flavorings used in alternative tobacco products to assess their impact on cardiovascular health.

The first part of the study comprised a population of nine nonsmokers, six nonmenthol cigarette smokers, and six menthol cigarette smokers without cardiovascular disease. The researchers isolated venous endothelial cells from each participant.

Overall, cells from both nonmenthol and menthol cigarette smokers had significantly lower nitric oxide production compared with nonsmokers (P = .003 and P = .012, respectively). In addition, the flavoring compounds menthol and eugenol impaired nitric oxide production in the cells of healthy individuals.

“Increased inflammation and a loss of nitric oxide are some of the first changes to occur leading up to cardiovascular disease and events like heart attacks and stroke, so they are considered early predictors of heart disease,” Dr. Fetterman said in a statement, adding that the “findings suggest that these flavoring additives may have serious health consequences.”

Carpe89/ThinkStock

SOURCE: Fetterman J et al. Arterioscler Thromb Vasc Biol. 2018. doi: 10.1161/ATVBAHA.118.311156.

©ASCO/Scott Morgan 2018

CHICAGO—The investigational drug ivosidenib, an inhibitor of the mutant IDH1 enzyme, achieved complete remission (CR) rates of 32% and an overall response rate of 42% in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML) and IDH1 mutation, according to investigators.

In addition, overall survival (OS) in patients who achieved CR more than doubled compared with those in the overall study population.

Fewer patients with CR had febrile neutropenia and infectious complications, and 25% of patients with CR were able to clear the IDH1 clone.

 Duration of response was 6.5 months with the investigational drug.

Investigators reported the grade 3/4 toxicities could be managed with supportive care, were not fatal, and some patients still achieved responses.

IDH1 mutation, first identified almost 10 years ago with the sequencing of the first AML cancer genome, is a recurrent mutation in over 10% of patients with AML.

Mutated IDH1, reported in several malignancies, results in impaired cellular differentiation.  Ivosidenib is a first-in-class oral therapy designed to inhibit the mutant IDH1 enzyme.

Phase 1 study (NCT02074839)

The phase 1 dose-escalation and dose expansion study specifically enrolled patients with R/RAML with mutated IDH1.

Daniel A. Pollyea, MD, of the Colorado University School of Medicine in Aurora, reported the data from 2 of the dose expansion cohorts as well as 35 patients from the dose escalation cohort at the 2018 ASCO Annual Meeting (abstract 7000).

All patients received ivosidenib 500 mg daily.

CR/CRh (CR with partial hematologic recovery; defined as morphologic remission with recovery of neutrophils to at least 500/mm3 and recovery of platelets to at least 50,000/µL) was the primary efficacy endpoint.

Of 179 patients in the primary efficacy cohort, 10% were still receiving treatment at the time of the presentation.

While most patients discontinued due to disease progression, 10% came off therapy for stem cell transplantation. Median duration of treatment was 4 months.

Patients were a median 67 years of age. Approximately 1/3 had secondary AML.

Patients had received a median of 2 prior therapies and approximately 1/4 had relapsed after transplantation.

Fifty-nine percent were refractory to induction or reinduction therapy.

Toxicity

Dr Pollyea considered adverse events to be as expected for a relapsed/refractory AML population.

However, he called out 3 for special mention—leukocytosis, ECG QT prolongation, and IDH differentiation syndrome—none of which was fatal.

Eight percent of patients had grade 3 or 4 leukocytosis, some of which were mechanistically induced from treatment.

About 10% of patients had grade 3 or 4 QT prolongation.

And grade 3 or 4 differentiation syndrome was reported for approximately 5% of patients.

In 19 patients with any grade differentiation syndrome, CR was reported for 5 patients. The message: patients experiencing this adverse event can be managed with supportive care, continue treatment, and still respond.

All adverse events were managed with supportive care measures, including concomitant medications, and ivosidenib dose modifications as required.

CR/CRh was 32% for the efficacy cohort; median time to response was 2 months and median time of response was 8.2 months. CR rate was 24%. Investigator-reported International Working Group categorized ORR was 42%.

The median OS was 9 months for the entire cohort and 18.8 months for patients who achieved CR/CRh.

Dr Pollyea reported that transfusion independence—defined as no need for transfusion for 56 days—was achieved in all CR patients, 75% of CRh patients, and even in a proportion of nonresponders.

Investigtors observed febrile neutropenia and grade 3 or 4 infectious complications in fewer patients who achieved CR/CRh.

Of note was the observation that 23% of patients who achieved CR/CRh were able to clear the mutant IDH1 clone. Patients who did not respond still harbored the IDH1 clone, Dr Pollyea reported.

These results reported at ASCO are an update from those simultaneously published in NEJM.

The study was supported by Agios Pharmaceuticals.

Ivosidenib is being evaluated alone and in combination in other clinical trials. 

©ASCO/Scott Morgan 2018

CHICAGO—The investigational drug ivosidenib, an inhibitor of the mutant IDH1 enzyme, achieved complete remission (CR) rates of 32% and an overall response rate of 42% in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML) and IDH1 mutation, according to investigators.

In addition, overall survival (OS) in patients who achieved CR more than doubled compared with those in the overall study population.

Fewer patients with CR had febrile neutropenia and infectious complications, and 25% of patients with CR were able to clear the IDH1 clone.

 Duration of response was 6.5 months with the investigational drug.

Investigators reported the grade 3/4 toxicities could be managed with supportive care, were not fatal, and some patients still achieved responses.

IDH1 mutation, first identified almost 10 years ago with the sequencing of the first AML cancer genome, is a recurrent mutation in over 10% of patients with AML.

Mutated IDH1, reported in several malignancies, results in impaired cellular differentiation.  Ivosidenib is a first-in-class oral therapy designed to inhibit the mutant IDH1 enzyme.

Phase 1 study (NCT02074839)

The phase 1 dose-escalation and dose expansion study specifically enrolled patients with R/RAML with mutated IDH1.

Daniel A. Pollyea, MD, of the Colorado University School of Medicine in Aurora, reported the data from 2 of the dose expansion cohorts as well as 35 patients from the dose escalation cohort at the 2018 ASCO Annual Meeting (abstract 7000).

All patients received ivosidenib 500 mg daily.

CR/CRh (CR with partial hematologic recovery; defined as morphologic remission with recovery of neutrophils to at least 500/mm3 and recovery of platelets to at least 50,000/µL) was the primary efficacy endpoint.

Of 179 patients in the primary efficacy cohort, 10% were still receiving treatment at the time of the presentation.

While most patients discontinued due to disease progression, 10% came off therapy for stem cell transplantation. Median duration of treatment was 4 months.

Patients were a median 67 years of age. Approximately 1/3 had secondary AML.

Patients had received a median of 2 prior therapies and approximately 1/4 had relapsed after transplantation.

Fifty-nine percent were refractory to induction or reinduction therapy.

Toxicity

Dr Pollyea considered adverse events to be as expected for a relapsed/refractory AML population.

However, he called out 3 for special mention—leukocytosis, ECG QT prolongation, and IDH differentiation syndrome—none of which was fatal.

Eight percent of patients had grade 3 or 4 leukocytosis, some of which were mechanistically induced from treatment.

About 10% of patients had grade 3 or 4 QT prolongation.

And grade 3 or 4 differentiation syndrome was reported for approximately 5% of patients.

In 19 patients with any grade differentiation syndrome, CR was reported for 5 patients. The message: patients experiencing this adverse event can be managed with supportive care, continue treatment, and still respond.

All adverse events were managed with supportive care measures, including concomitant medications, and ivosidenib dose modifications as required.

CR/CRh was 32% for the efficacy cohort; median time to response was 2 months and median time of response was 8.2 months. CR rate was 24%. Investigator-reported International Working Group categorized ORR was 42%.

The median OS was 9 months for the entire cohort and 18.8 months for patients who achieved CR/CRh.

Dr Pollyea reported that transfusion independence—defined as no need for transfusion for 56 days—was achieved in all CR patients, 75% of CRh patients, and even in a proportion of nonresponders.

Investigtors observed febrile neutropenia and grade 3 or 4 infectious complications in fewer patients who achieved CR/CRh.

Of note was the observation that 23% of patients who achieved CR/CRh were able to clear the mutant IDH1 clone. Patients who did not respond still harbored the IDH1 clone, Dr Pollyea reported.

These results reported at ASCO are an update from those simultaneously published in NEJM.

The study was supported by Agios Pharmaceuticals.

Ivosidenib is being evaluated alone and in combination in other clinical trials. 

©ASCO/Scott Morgan 2018

CHICAGO—The investigational drug ivosidenib, an inhibitor of the mutant IDH1 enzyme, achieved complete remission (CR) rates of 32% and an overall response rate of 42% in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML) and IDH1 mutation, according to investigators.

In addition, overall survival (OS) in patients who achieved CR more than doubled compared with those in the overall study population.

Fewer patients with CR had febrile neutropenia and infectious complications, and 25% of patients with CR were able to clear the IDH1 clone.

 Duration of response was 6.5 months with the investigational drug.

Investigators reported the grade 3/4 toxicities could be managed with supportive care, were not fatal, and some patients still achieved responses.

IDH1 mutation, first identified almost 10 years ago with the sequencing of the first AML cancer genome, is a recurrent mutation in over 10% of patients with AML.

Mutated IDH1, reported in several malignancies, results in impaired cellular differentiation.  Ivosidenib is a first-in-class oral therapy designed to inhibit the mutant IDH1 enzyme.

Phase 1 study (NCT02074839)

The phase 1 dose-escalation and dose expansion study specifically enrolled patients with R/RAML with mutated IDH1.

Daniel A. Pollyea, MD, of the Colorado University School of Medicine in Aurora, reported the data from 2 of the dose expansion cohorts as well as 35 patients from the dose escalation cohort at the 2018 ASCO Annual Meeting (abstract 7000).

All patients received ivosidenib 500 mg daily.

CR/CRh (CR with partial hematologic recovery; defined as morphologic remission with recovery of neutrophils to at least 500/mm3 and recovery of platelets to at least 50,000/µL) was the primary efficacy endpoint.

Of 179 patients in the primary efficacy cohort, 10% were still receiving treatment at the time of the presentation.

While most patients discontinued due to disease progression, 10% came off therapy for stem cell transplantation. Median duration of treatment was 4 months.

Patients were a median 67 years of age. Approximately 1/3 had secondary AML.

Patients had received a median of 2 prior therapies and approximately 1/4 had relapsed after transplantation.

Fifty-nine percent were refractory to induction or reinduction therapy.

Toxicity

Dr Pollyea considered adverse events to be as expected for a relapsed/refractory AML population.

However, he called out 3 for special mention—leukocytosis, ECG QT prolongation, and IDH differentiation syndrome—none of which was fatal.

Eight percent of patients had grade 3 or 4 leukocytosis, some of which were mechanistically induced from treatment.

About 10% of patients had grade 3 or 4 QT prolongation.

And grade 3 or 4 differentiation syndrome was reported for approximately 5% of patients.

In 19 patients with any grade differentiation syndrome, CR was reported for 5 patients. The message: patients experiencing this adverse event can be managed with supportive care, continue treatment, and still respond.

All adverse events were managed with supportive care measures, including concomitant medications, and ivosidenib dose modifications as required.

CR/CRh was 32% for the efficacy cohort; median time to response was 2 months and median time of response was 8.2 months. CR rate was 24%. Investigator-reported International Working Group categorized ORR was 42%.

The median OS was 9 months for the entire cohort and 18.8 months for patients who achieved CR/CRh.

Dr Pollyea reported that transfusion independence—defined as no need for transfusion for 56 days—was achieved in all CR patients, 75% of CRh patients, and even in a proportion of nonresponders.

Investigtors observed febrile neutropenia and grade 3 or 4 infectious complications in fewer patients who achieved CR/CRh.

Of note was the observation that 23% of patients who achieved CR/CRh were able to clear the mutant IDH1 clone. Patients who did not respond still harbored the IDH1 clone, Dr Pollyea reported.

These results reported at ASCO are an update from those simultaneously published in NEJM.

The study was supported by Agios Pharmaceuticals.

Ivosidenib is being evaluated alone and in combination in other clinical trials. 

Photo courtesy of Merck

The US Food and Drug Administration (FDA) granted accelerated approval to the anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).

The indication also includes patients who have relapsed after 2 or more prior lines of therapy.

Pembrolizumab had received priority review for PMBCL late last year and also has orphan drug designation and breakthrough therapy designation for this indication.

The FDA based its approval on data from the KEYNOTE-170 (NCT02576990 ) trial.

Investigators enrolled 53 patients onto the multicenter, open-label, single-arm trial. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression.

Patients whose disease did not progress received the drug for up to 24 months.

Patient characteristics

Patients were a median age of 33 years (range, 20 – 61), 43% were male, 92% white, 43% had an ECOG performance status of 0, and 57% had an ECOG performance status of 1.

Almost half (49%) had relapsed disease, and 36% had primary refractory disease.

About a quarter (26%) had undergone prior autologous hematopoietic stem cell transplant, and 32% had prior radiation therapy.

All patients had received prior rituximab.

Results

At a median follow-up of 9.7 months, the overall response rate was 45% (24 responders), including 11% complete responses and 34% partial responses.

The median duration of response was not reached during the follow-up period and ranged from a median 1.1 to 19.2 months.

Median time to first objective response was 2.8 months (range, 2.1 – 8.5). Accordingly, investigators do not recommend pembrolizumab for PMBCL patients who require urgent cytoreductive therapy.

Safety

The most common adverse events occurring in 10% or more of patients were musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), fatigue (23%), cough (26%), dyspnea (21%), diarrhea (13%), abdominal pain (13%), nausea (11%), arrhythmia (11%), and headache (11%).

Eight percent of patients discontinued treatment, and 15% interrupted treatment due to adverse reactions.

Adverse events requiring systemic corticosteroid therapy occurred in 25% of patients.

Serious adverse events occurred in 26% and included arrhythmia (4 %), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%).

Six (11%) patients died within 30 days of start of treatment.

The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks.  The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Additional indications for pembrolizumab include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, and cervical cancer.

The full prescribing information is available on the FDA website.

Pembrolizumab (Keytruda) is a product of Merck & Co, Inc. 

Photo courtesy of Merck

The US Food and Drug Administration (FDA) granted accelerated approval to the anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).

The indication also includes patients who have relapsed after 2 or more prior lines of therapy.

Pembrolizumab had received priority review for PMBCL late last year and also has orphan drug designation and breakthrough therapy designation for this indication.

The FDA based its approval on data from the KEYNOTE-170 (NCT02576990 ) trial.

Investigators enrolled 53 patients onto the multicenter, open-label, single-arm trial. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression.

Patients whose disease did not progress received the drug for up to 24 months.

Patient characteristics

Patients were a median age of 33 years (range, 20 – 61), 43% were male, 92% white, 43% had an ECOG performance status of 0, and 57% had an ECOG performance status of 1.

Almost half (49%) had relapsed disease, and 36% had primary refractory disease.

About a quarter (26%) had undergone prior autologous hematopoietic stem cell transplant, and 32% had prior radiation therapy.

All patients had received prior rituximab.

Results

At a median follow-up of 9.7 months, the overall response rate was 45% (24 responders), including 11% complete responses and 34% partial responses.

The median duration of response was not reached during the follow-up period and ranged from a median 1.1 to 19.2 months.

Median time to first objective response was 2.8 months (range, 2.1 – 8.5). Accordingly, investigators do not recommend pembrolizumab for PMBCL patients who require urgent cytoreductive therapy.

Safety

The most common adverse events occurring in 10% or more of patients were musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), fatigue (23%), cough (26%), dyspnea (21%), diarrhea (13%), abdominal pain (13%), nausea (11%), arrhythmia (11%), and headache (11%).

Eight percent of patients discontinued treatment, and 15% interrupted treatment due to adverse reactions.

Adverse events requiring systemic corticosteroid therapy occurred in 25% of patients.

Serious adverse events occurred in 26% and included arrhythmia (4 %), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%).

Six (11%) patients died within 30 days of start of treatment.

The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks.  The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Additional indications for pembrolizumab include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, and cervical cancer.

The full prescribing information is available on the FDA website.

Pembrolizumab (Keytruda) is a product of Merck & Co, Inc. 

Photo courtesy of Merck

The US Food and Drug Administration (FDA) granted accelerated approval to the anti-PD-1 therapy pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL).

The indication also includes patients who have relapsed after 2 or more prior lines of therapy.

Pembrolizumab had received priority review for PMBCL late last year and also has orphan drug designation and breakthrough therapy designation for this indication.

The FDA based its approval on data from the KEYNOTE-170 (NCT02576990 ) trial.

Investigators enrolled 53 patients onto the multicenter, open-label, single-arm trial. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression.

Patients whose disease did not progress received the drug for up to 24 months.

Patient characteristics

Patients were a median age of 33 years (range, 20 – 61), 43% were male, 92% white, 43% had an ECOG performance status of 0, and 57% had an ECOG performance status of 1.

Almost half (49%) had relapsed disease, and 36% had primary refractory disease.

About a quarter (26%) had undergone prior autologous hematopoietic stem cell transplant, and 32% had prior radiation therapy.

All patients had received prior rituximab.

Results

At a median follow-up of 9.7 months, the overall response rate was 45% (24 responders), including 11% complete responses and 34% partial responses.

The median duration of response was not reached during the follow-up period and ranged from a median 1.1 to 19.2 months.

Median time to first objective response was 2.8 months (range, 2.1 – 8.5). Accordingly, investigators do not recommend pembrolizumab for PMBCL patients who require urgent cytoreductive therapy.

Safety

The most common adverse events occurring in 10% or more of patients were musculoskeletal pain (30%), upper respiratory tract infection (28%), pyrexia (28%), fatigue (23%), cough (26%), dyspnea (21%), diarrhea (13%), abdominal pain (13%), nausea (11%), arrhythmia (11%), and headache (11%).

Eight percent of patients discontinued treatment, and 15% interrupted treatment due to adverse reactions.

Adverse events requiring systemic corticosteroid therapy occurred in 25% of patients.

Serious adverse events occurred in 26% and included arrhythmia (4 %), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%).

Six (11%) patients died within 30 days of start of treatment.

The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks.  The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Additional indications for pembrolizumab include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, and cervical cancer.

The full prescribing information is available on the FDA website.

Pembrolizumab (Keytruda) is a product of Merck & Co, Inc. 

The FP recognized the growth as an early nevus sebaceous (NS).

NS may be present at birth or noted in early childhood and occurs in males and females equally. In early stages of development, it appears skin-colored and waxy. Because of the potential for malignant transformation, particularly following puberty, many authors have recommended early complete plastic surgical excision. However, in a retrospective analysis of 757 cases of NS from 1996 to 2002 in children <16 years, investigators found no malignancies and questioned the need for prophylactic surgical removal.

The FP emphasized that this condition was benign and would likely get darker and more raised over time. He said that he would keep an eye on it during future visits and that the boy could choose to have it removed when he became an adult. The FP explained that reasons for removal include cosmetic issues and the prevention of malignant changes.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine, 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized the growth as an early nevus sebaceous (NS).

NS may be present at birth or noted in early childhood and occurs in males and females equally. In early stages of development, it appears skin-colored and waxy. Because of the potential for malignant transformation, particularly following puberty, many authors have recommended early complete plastic surgical excision. However, in a retrospective analysis of 757 cases of NS from 1996 to 2002 in children <16 years, investigators found no malignancies and questioned the need for prophylactic surgical removal.

The FP emphasized that this condition was benign and would likely get darker and more raised over time. He said that he would keep an eye on it during future visits and that the boy could choose to have it removed when he became an adult. The FP explained that reasons for removal include cosmetic issues and the prevention of malignant changes.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine, 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized the growth as an early nevus sebaceous (NS).

NS may be present at birth or noted in early childhood and occurs in males and females equally. In early stages of development, it appears skin-colored and waxy. Because of the potential for malignant transformation, particularly following puberty, many authors have recommended early complete plastic surgical excision. However, in a retrospective analysis of 757 cases of NS from 1996 to 2002 in children <16 years, investigators found no malignancies and questioned the need for prophylactic surgical removal.

The FP emphasized that this condition was benign and would likely get darker and more raised over time. He said that he would keep an eye on it during future visits and that the boy could choose to have it removed when he became an adult. The FP explained that reasons for removal include cosmetic issues and the prevention of malignant changes.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine, 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

SAN DIEGO – Individuals with opioid use disorder generally embraced the idea of using a novel mobile application to learn about recovery options and medication-assisted treatment, according to results from a pilot study.

Doug Brunk/MDedge News

“We found that, after participants engaged with our mobile app, their interest for recovery and attitudes about recovery improved,” lead study author Patricia Cavazos-Rehg, PhD, of the department of psychiatry at Washington University in St. Louis, said in an interview at the annual meeting of the College on Problems of Drug Dependence. “We were not expecting results to be so positive, and these findings are very promising because they suggest that individuals may not have interest in or be reluctant to engage in treatment. But we can engage them with a tool that will get them interested and move them toward treatment recovery.”

Dr. Cavazos-Rehg and her associates set out to examine the effectiveness of a mobile application called “uMAT-R,” which includes evidence-based health information about opioid use disorder recovery and medication-assisted treatment (MAT). The app is being develop in partnership with iTether, an Arizona-based mobile health software company. Material for the user is derived from the Substance Abuse and Mental Health Services Administration’s online handbook, “Decisions in Recovery: Treatment for Opioid Disorders,” and is divided into consumer-friendly content modules that provide information on MAT, including costs, latest research findings, and potential side effects.

For the study, researchers recruited 161 individuals 18 years of age and older from three opioid-focused groups on Reddit to pilot the use of uMAT-R. To be eligible, they had to be a U.S. resident, be fluent in English, have misused opioids in the past 30 days, and not currently be using medication-assisted treatment. Participants had access to the app for 1 month, and the researchers administered a baseline questionnaire that assessed demographics, opioid dependence, and history of treatment. They also administered pre- and postapplication engagement questionnaires that assessed attitudes toward MAT, treatment interest, and usefulness of the app.

Of the 161 invited participants, 44 downloaded the app, and 26 completed all content modules and all pre- and postapp assessments. The median age of the 26 participants was 28 years; 65% were male, and 88% were non-Hispanic white. Nearly all (96%) met criteria for opioid dependence, and 12% had received treatment for opioid misuse in the past 6 months. Dr. Cavazos-Rehg and her associates found that only 32% expressed interest in starting treatment for their opioid use disorder before using the app, compared with 48% after using the app, a difference that reached statistical significance (P = 0.046). Feedback from participants was mostly positive. For example, 92% agreed that the app includes useful tips on how to make life better; 88% would consult the app if they had to make a decision about their recovery; 88% believed the app has a positive outlook; 84% said the app helped them have a better understanding of options for recovery, and 84% said they learned something new from the app.

In addition, scores on the MAT attitudes scale rose from a mean of 3.3 to a mean of 3.5 (P = 0.044).

“We are in the pilot phase of our research, so it is exciting for us to already observe statistically significant findings,” Dr. Cavazos-Rehg said. “We want to develop a mobile app that will teach individuals who have opioid use disorder about their recovery options so that we can nudge them towards considering recovery, and our findings indicate some success with this goal.”

Next, she and her associates plan to pair use of the app with traditional in-person care among pregnant women with opioid use disorders. “Even if people are engaged in treatment, they still only see a therapist or a clinician once or twice a week,” she said. “We want to be able to use a mobile health treatment to support their needs while they are outside of treatment.”

The study was funded by a grant from the National Institutes of Health. Dr. Cavazos-Rehg reported having no financial disclosures.

[email protected]

SAN DIEGO – Individuals with opioid use disorder generally embraced the idea of using a novel mobile application to learn about recovery options and medication-assisted treatment, according to results from a pilot study.

Doug Brunk/MDedge News

“We found that, after participants engaged with our mobile app, their interest for recovery and attitudes about recovery improved,” lead study author Patricia Cavazos-Rehg, PhD, of the department of psychiatry at Washington University in St. Louis, said in an interview at the annual meeting of the College on Problems of Drug Dependence. “We were not expecting results to be so positive, and these findings are very promising because they suggest that individuals may not have interest in or be reluctant to engage in treatment. But we can engage them with a tool that will get them interested and move them toward treatment recovery.”

Dr. Cavazos-Rehg and her associates set out to examine the effectiveness of a mobile application called “uMAT-R,” which includes evidence-based health information about opioid use disorder recovery and medication-assisted treatment (MAT). The app is being develop in partnership with iTether, an Arizona-based mobile health software company. Material for the user is derived from the Substance Abuse and Mental Health Services Administration’s online handbook, “Decisions in Recovery: Treatment for Opioid Disorders,” and is divided into consumer-friendly content modules that provide information on MAT, including costs, latest research findings, and potential side effects.

For the study, researchers recruited 161 individuals 18 years of age and older from three opioid-focused groups on Reddit to pilot the use of uMAT-R. To be eligible, they had to be a U.S. resident, be fluent in English, have misused opioids in the past 30 days, and not currently be using medication-assisted treatment. Participants had access to the app for 1 month, and the researchers administered a baseline questionnaire that assessed demographics, opioid dependence, and history of treatment. They also administered pre- and postapplication engagement questionnaires that assessed attitudes toward MAT, treatment interest, and usefulness of the app.

Of the 161 invited participants, 44 downloaded the app, and 26 completed all content modules and all pre- and postapp assessments. The median age of the 26 participants was 28 years; 65% were male, and 88% were non-Hispanic white. Nearly all (96%) met criteria for opioid dependence, and 12% had received treatment for opioid misuse in the past 6 months. Dr. Cavazos-Rehg and her associates found that only 32% expressed interest in starting treatment for their opioid use disorder before using the app, compared with 48% after using the app, a difference that reached statistical significance (P = 0.046). Feedback from participants was mostly positive. For example, 92% agreed that the app includes useful tips on how to make life better; 88% would consult the app if they had to make a decision about their recovery; 88% believed the app has a positive outlook; 84% said the app helped them have a better understanding of options for recovery, and 84% said they learned something new from the app.

In addition, scores on the MAT attitudes scale rose from a mean of 3.3 to a mean of 3.5 (P = 0.044).

“We are in the pilot phase of our research, so it is exciting for us to already observe statistically significant findings,” Dr. Cavazos-Rehg said. “We want to develop a mobile app that will teach individuals who have opioid use disorder about their recovery options so that we can nudge them towards considering recovery, and our findings indicate some success with this goal.”

Next, she and her associates plan to pair use of the app with traditional in-person care among pregnant women with opioid use disorders. “Even if people are engaged in treatment, they still only see a therapist or a clinician once or twice a week,” she said. “We want to be able to use a mobile health treatment to support their needs while they are outside of treatment.”

The study was funded by a grant from the National Institutes of Health. Dr. Cavazos-Rehg reported having no financial disclosures.

[email protected]

SAN DIEGO – Individuals with opioid use disorder generally embraced the idea of using a novel mobile application to learn about recovery options and medication-assisted treatment, according to results from a pilot study.

Doug Brunk/MDedge News

“We found that, after participants engaged with our mobile app, their interest for recovery and attitudes about recovery improved,” lead study author Patricia Cavazos-Rehg, PhD, of the department of psychiatry at Washington University in St. Louis, said in an interview at the annual meeting of the College on Problems of Drug Dependence. “We were not expecting results to be so positive, and these findings are very promising because they suggest that individuals may not have interest in or be reluctant to engage in treatment. But we can engage them with a tool that will get them interested and move them toward treatment recovery.”

Dr. Cavazos-Rehg and her associates set out to examine the effectiveness of a mobile application called “uMAT-R,” which includes evidence-based health information about opioid use disorder recovery and medication-assisted treatment (MAT). The app is being develop in partnership with iTether, an Arizona-based mobile health software company. Material for the user is derived from the Substance Abuse and Mental Health Services Administration’s online handbook, “Decisions in Recovery: Treatment for Opioid Disorders,” and is divided into consumer-friendly content modules that provide information on MAT, including costs, latest research findings, and potential side effects.

For the study, researchers recruited 161 individuals 18 years of age and older from three opioid-focused groups on Reddit to pilot the use of uMAT-R. To be eligible, they had to be a U.S. resident, be fluent in English, have misused opioids in the past 30 days, and not currently be using medication-assisted treatment. Participants had access to the app for 1 month, and the researchers administered a baseline questionnaire that assessed demographics, opioid dependence, and history of treatment. They also administered pre- and postapplication engagement questionnaires that assessed attitudes toward MAT, treatment interest, and usefulness of the app.

Of the 161 invited participants, 44 downloaded the app, and 26 completed all content modules and all pre- and postapp assessments. The median age of the 26 participants was 28 years; 65% were male, and 88% were non-Hispanic white. Nearly all (96%) met criteria for opioid dependence, and 12% had received treatment for opioid misuse in the past 6 months. Dr. Cavazos-Rehg and her associates found that only 32% expressed interest in starting treatment for their opioid use disorder before using the app, compared with 48% after using the app, a difference that reached statistical significance (P = 0.046). Feedback from participants was mostly positive. For example, 92% agreed that the app includes useful tips on how to make life better; 88% would consult the app if they had to make a decision about their recovery; 88% believed the app has a positive outlook; 84% said the app helped them have a better understanding of options for recovery, and 84% said they learned something new from the app.

In addition, scores on the MAT attitudes scale rose from a mean of 3.3 to a mean of 3.5 (P = 0.044).

“We are in the pilot phase of our research, so it is exciting for us to already observe statistically significant findings,” Dr. Cavazos-Rehg said. “We want to develop a mobile app that will teach individuals who have opioid use disorder about their recovery options so that we can nudge them towards considering recovery, and our findings indicate some success with this goal.”

Next, she and her associates plan to pair use of the app with traditional in-person care among pregnant women with opioid use disorders. “Even if people are engaged in treatment, they still only see a therapist or a clinician once or twice a week,” she said. “We want to be able to use a mobile health treatment to support their needs while they are outside of treatment.”

The study was funded by a grant from the National Institutes of Health. Dr. Cavazos-Rehg reported having no financial disclosures.

[email protected]