SAN ANTONIO – Half of premenopausal breast cancer patients who had completed chemotherapy conceived by intercourse alone within 3 months of beginning to attempt conception, a study showed.

This single-center study provides some guidance for women and the physicians caring for them that an attempt at natural conception is worthwhile if ovarian function has returned after chemotherapy, said Nikita Sinha.

Speaking at the annual meeting of the American Society for Reproductive Medicine, Ms. Sinha, a medical student at the University of California, San Francisco, said that this is a worthwhile strategy, “even for patients with limited ovarian reserve, prior to using cryopreserved tissue.” Cytotoxicity of chemotherapy was not associated with decreased chances for conception, she said.

Ms. Sinha and her colleagues designed a prospective cohort study to follow women aged 18-44 years who had been diagnosed with breast cancer and had received a fertility preservation consult. A total of 297 women who had completed cancer treatment were contacted and asked to complete a survey that asked questions about their oncologic and reproductive history. Of these, 200 (67%) completed the survey, but 43 more patients were excluded because they had not received chemotherapy.

Of the remaining 157 women, 40 (25%) attempted to conceive. Return of ovarian function occurred in 36 of the 40 women (90%). Of these 36 women, 4 also began their attempts to conceive with assisted reproductive technology (ART) because of age, previous history of infertility, or a preimplantation genetic diagnosis of the BRCA mutation. Thus, a total of eight patients (20%) first attempted to conceive with ART.

Three-fourths of women in both groups had eggs or embryos cryopreserved before their chemotherapy. In the ART group, a total of five women (62.5%) became pregnant: One first attempted intrauterine insemination and became pregnant; two first attempted pregnancy by egg donation, and one became pregnant; and three of five women who attempted embryo transfer from cryopreserved eggs or embryos became pregnant.

Of the 32 women who first attempted to conceive by intercourse, 18 became pregnant after 3 months, and 16 women had a live birth, for a 50% live birth rate for this group. Of the remaining 14 women who did not become pregnant by intercourse, 8 went on to attempt conception by ART.

Of these eight women, intrauterine insemination was attempted by three, with two resulting pregnancies. The single patient who used letrozole became pregnant. Of the four patients who attempted frozen embryo transfer, two became pregnant, for a total of five pregnancies (62.5%).

Comparing the 18 women who became pregnant with the 14 women who did not, Ms. Sinha and her colleagues found no significant differences in age, parity, hormone receptor status, pre- or postchemotherapy antral follicle count, type of chemotherapy, or time since chemotherapy. Receiving leuprolide acetate during therapy was not a significant factor.

Of the patients who became pregnant, 2 of 28 (7%) have had a recurrence of their breast cancer; both of these patients are estrogen receptor positive, said Ms. Sinha. One of the 12 patients who didn’t become pregnant also has had a recurrence; she is estrogen receptor negative.

In this study, the winnowing process of patient selection resulted in a limited sample size, with the potential for selection bias, said Ms. Sinha. Data collection is ongoing for breast cancer patients who receive fertility preservation consultations at her facility, she said.

The women trying to conceive were, on average, 37 years old at their initial attempt at conception, and had completed chemotherapy about 4 years ago. Most patients received cytotoxic chemotherapy, and 25 (63%) had estrogen receptor–positive cancer.

Previous work had shown that up to 80% of women of reproductive age will have some ovarian function resume after treatment with gonadotoxic chemotherapy agents, said Ms. Sinha.

However, the fertility risk for cancer survivors is twofold, said Ms. Sinha. “While acute ovarian failure is a well-known risk, there remains an increased risk of early menopause despite resumption of menses, especially in younger aged women” who are cancer survivors, she said.

Ms. Sinha reported that her work was supported by the University of California, San Francisco Clinical and Translational Science Institute.

[email protected]

On Twitter @karioakes

SAN ANTONIO – Half of premenopausal breast cancer patients who had completed chemotherapy conceived by intercourse alone within 3 months of beginning to attempt conception, a study showed.

This single-center study provides some guidance for women and the physicians caring for them that an attempt at natural conception is worthwhile if ovarian function has returned after chemotherapy, said Nikita Sinha.

Speaking at the annual meeting of the American Society for Reproductive Medicine, Ms. Sinha, a medical student at the University of California, San Francisco, said that this is a worthwhile strategy, “even for patients with limited ovarian reserve, prior to using cryopreserved tissue.” Cytotoxicity of chemotherapy was not associated with decreased chances for conception, she said.

Ms. Sinha and her colleagues designed a prospective cohort study to follow women aged 18-44 years who had been diagnosed with breast cancer and had received a fertility preservation consult. A total of 297 women who had completed cancer treatment were contacted and asked to complete a survey that asked questions about their oncologic and reproductive history. Of these, 200 (67%) completed the survey, but 43 more patients were excluded because they had not received chemotherapy.

Of the remaining 157 women, 40 (25%) attempted to conceive. Return of ovarian function occurred in 36 of the 40 women (90%). Of these 36 women, 4 also began their attempts to conceive with assisted reproductive technology (ART) because of age, previous history of infertility, or a preimplantation genetic diagnosis of the BRCA mutation. Thus, a total of eight patients (20%) first attempted to conceive with ART.

Three-fourths of women in both groups had eggs or embryos cryopreserved before their chemotherapy. In the ART group, a total of five women (62.5%) became pregnant: One first attempted intrauterine insemination and became pregnant; two first attempted pregnancy by egg donation, and one became pregnant; and three of five women who attempted embryo transfer from cryopreserved eggs or embryos became pregnant.

Of the 32 women who first attempted to conceive by intercourse, 18 became pregnant after 3 months, and 16 women had a live birth, for a 50% live birth rate for this group. Of the remaining 14 women who did not become pregnant by intercourse, 8 went on to attempt conception by ART.

Of these eight women, intrauterine insemination was attempted by three, with two resulting pregnancies. The single patient who used letrozole became pregnant. Of the four patients who attempted frozen embryo transfer, two became pregnant, for a total of five pregnancies (62.5%).

Comparing the 18 women who became pregnant with the 14 women who did not, Ms. Sinha and her colleagues found no significant differences in age, parity, hormone receptor status, pre- or postchemotherapy antral follicle count, type of chemotherapy, or time since chemotherapy. Receiving leuprolide acetate during therapy was not a significant factor.

Of the patients who became pregnant, 2 of 28 (7%) have had a recurrence of their breast cancer; both of these patients are estrogen receptor positive, said Ms. Sinha. One of the 12 patients who didn’t become pregnant also has had a recurrence; she is estrogen receptor negative.

In this study, the winnowing process of patient selection resulted in a limited sample size, with the potential for selection bias, said Ms. Sinha. Data collection is ongoing for breast cancer patients who receive fertility preservation consultations at her facility, she said.

The women trying to conceive were, on average, 37 years old at their initial attempt at conception, and had completed chemotherapy about 4 years ago. Most patients received cytotoxic chemotherapy, and 25 (63%) had estrogen receptor–positive cancer.

Previous work had shown that up to 80% of women of reproductive age will have some ovarian function resume after treatment with gonadotoxic chemotherapy agents, said Ms. Sinha.

However, the fertility risk for cancer survivors is twofold, said Ms. Sinha. “While acute ovarian failure is a well-known risk, there remains an increased risk of early menopause despite resumption of menses, especially in younger aged women” who are cancer survivors, she said.

Ms. Sinha reported that her work was supported by the University of California, San Francisco Clinical and Translational Science Institute.

[email protected]

On Twitter @karioakes

SAN ANTONIO – Half of premenopausal breast cancer patients who had completed chemotherapy conceived by intercourse alone within 3 months of beginning to attempt conception, a study showed.

This single-center study provides some guidance for women and the physicians caring for them that an attempt at natural conception is worthwhile if ovarian function has returned after chemotherapy, said Nikita Sinha.

Speaking at the annual meeting of the American Society for Reproductive Medicine, Ms. Sinha, a medical student at the University of California, San Francisco, said that this is a worthwhile strategy, “even for patients with limited ovarian reserve, prior to using cryopreserved tissue.” Cytotoxicity of chemotherapy was not associated with decreased chances for conception, she said.

Ms. Sinha and her colleagues designed a prospective cohort study to follow women aged 18-44 years who had been diagnosed with breast cancer and had received a fertility preservation consult. A total of 297 women who had completed cancer treatment were contacted and asked to complete a survey that asked questions about their oncologic and reproductive history. Of these, 200 (67%) completed the survey, but 43 more patients were excluded because they had not received chemotherapy.

Of the remaining 157 women, 40 (25%) attempted to conceive. Return of ovarian function occurred in 36 of the 40 women (90%). Of these 36 women, 4 also began their attempts to conceive with assisted reproductive technology (ART) because of age, previous history of infertility, or a preimplantation genetic diagnosis of the BRCA mutation. Thus, a total of eight patients (20%) first attempted to conceive with ART.

Three-fourths of women in both groups had eggs or embryos cryopreserved before their chemotherapy. In the ART group, a total of five women (62.5%) became pregnant: One first attempted intrauterine insemination and became pregnant; two first attempted pregnancy by egg donation, and one became pregnant; and three of five women who attempted embryo transfer from cryopreserved eggs or embryos became pregnant.

Of the 32 women who first attempted to conceive by intercourse, 18 became pregnant after 3 months, and 16 women had a live birth, for a 50% live birth rate for this group. Of the remaining 14 women who did not become pregnant by intercourse, 8 went on to attempt conception by ART.

Of these eight women, intrauterine insemination was attempted by three, with two resulting pregnancies. The single patient who used letrozole became pregnant. Of the four patients who attempted frozen embryo transfer, two became pregnant, for a total of five pregnancies (62.5%).

Comparing the 18 women who became pregnant with the 14 women who did not, Ms. Sinha and her colleagues found no significant differences in age, parity, hormone receptor status, pre- or postchemotherapy antral follicle count, type of chemotherapy, or time since chemotherapy. Receiving leuprolide acetate during therapy was not a significant factor.

Of the patients who became pregnant, 2 of 28 (7%) have had a recurrence of their breast cancer; both of these patients are estrogen receptor positive, said Ms. Sinha. One of the 12 patients who didn’t become pregnant also has had a recurrence; she is estrogen receptor negative.

In this study, the winnowing process of patient selection resulted in a limited sample size, with the potential for selection bias, said Ms. Sinha. Data collection is ongoing for breast cancer patients who receive fertility preservation consultations at her facility, she said.

The women trying to conceive were, on average, 37 years old at their initial attempt at conception, and had completed chemotherapy about 4 years ago. Most patients received cytotoxic chemotherapy, and 25 (63%) had estrogen receptor–positive cancer.

Previous work had shown that up to 80% of women of reproductive age will have some ovarian function resume after treatment with gonadotoxic chemotherapy agents, said Ms. Sinha.

However, the fertility risk for cancer survivors is twofold, said Ms. Sinha. “While acute ovarian failure is a well-known risk, there remains an increased risk of early menopause despite resumption of menses, especially in younger aged women” who are cancer survivors, she said.

Ms. Sinha reported that her work was supported by the University of California, San Francisco Clinical and Translational Science Institute.

[email protected]

On Twitter @karioakes

WASHINGTON – Standard infantile spasm therapies such as adrenocorticotropic hormone appear to be significantly more effective than nonstandard therapies, according to a prospective study presented at the annual meeting of the American Epilepsy Society.

If infants currently treated with nonstandard therapies switched to adrenocorticotropic hormone (ACTH), there would be an increase of “one additional responder for every four infants with infantile spasms,” according to Renee Shellhaas, MD, a pediatric neurologist at the University of Michigan, Ann Arbor.

Dr. Shellhaas and her colleagues conducted a prospective study of 352 infants recorded to have spasms in the National Infantile Spasms Consortium from 2012 to 2016 and compared successful responses with the use of ACTH and other standard therapies against those with nonstandard therapies. They defined a successful response as a patient who did not take any other medication for infantile spasms for 60 days and had no infantile spasms for 30 days after finishing 30 days of treatment. Infants were split into four treatment arms: ACTH (n = 150), vigabatrin (68), oral steroids (90), and nonstandard therapies (44). Nonstandard therapies included topiramate, levetiracetam, clobazam, zonisamide, ketogenic diet, oxcarbazepine, and phenobarbital.

The proportion of male infants across all arms was 50%-64%, with an average age of 6.2 months in the ACTH group, 5.5 months in the vigabatrin group, 6.7 months in the oral steroids group, and 5.5 months in the nonstandard group. A majority of infants across all arms had hypsarrhythmia on EEG, ranging from 57% to 84%.

Dr. Shellhaas and her colleagues sought to answer the question, “What would happen if this infant had been treated with ACTH instead of the given medication?” They controlled these comparisons for selection bias by weighting them for various factors that may have increased the odds of using the comparison treatment. They also controlled for potential medical center effects, but did not adjust for dosing regimen.

If the infants who had received nonstandard therapies had instead received ACTH, their response rate would have improved from 5% to 32%, according to this analysis (P less than .01).

In comparisons against other standard treatments, response rates would not have been significantly better if patients had instead received ACTH: 29% for vigabatrin vs. an estimated 37% for ACTH and 46% for oral steroids vs. an estimated 44% for ACTH.

If there was one thing to take away from this, it is that nonstandard therapies do not work nearly as well as ACTH or other standard treatments,” Dr. Shellhaas said. “It is crucial to treat these infants with treatments that are effective.”

Dr. Shellhaas and her associates uncovered certain clinical factors associated with treatment selections. Among infants with unknown infantile spasm etiology, 30% were given nonstandard treatment, whereas 47% received ACTH. Infants who were not already on antiepileptic drugs more often received nonstandard therapies than ACTH (45% vs. 17%).

However, ACTH was still more likely to be given over nonstandard therapies to infants who had hypsarrhythmia (84% vs. 57%) or a normal head circumference (77% vs. 57%).

Dr. Shellhaas reported no relevant financial disclosures. The Pediatric Epilepsy Research Foundation funded the study.

[email protected]

SOURCE: AES 2017 abstract 1.303

WASHINGTON – Standard infantile spasm therapies such as adrenocorticotropic hormone appear to be significantly more effective than nonstandard therapies, according to a prospective study presented at the annual meeting of the American Epilepsy Society.

If infants currently treated with nonstandard therapies switched to adrenocorticotropic hormone (ACTH), there would be an increase of “one additional responder for every four infants with infantile spasms,” according to Renee Shellhaas, MD, a pediatric neurologist at the University of Michigan, Ann Arbor.

Dr. Shellhaas and her colleagues conducted a prospective study of 352 infants recorded to have spasms in the National Infantile Spasms Consortium from 2012 to 2016 and compared successful responses with the use of ACTH and other standard therapies against those with nonstandard therapies. They defined a successful response as a patient who did not take any other medication for infantile spasms for 60 days and had no infantile spasms for 30 days after finishing 30 days of treatment. Infants were split into four treatment arms: ACTH (n = 150), vigabatrin (68), oral steroids (90), and nonstandard therapies (44). Nonstandard therapies included topiramate, levetiracetam, clobazam, zonisamide, ketogenic diet, oxcarbazepine, and phenobarbital.

The proportion of male infants across all arms was 50%-64%, with an average age of 6.2 months in the ACTH group, 5.5 months in the vigabatrin group, 6.7 months in the oral steroids group, and 5.5 months in the nonstandard group. A majority of infants across all arms had hypsarrhythmia on EEG, ranging from 57% to 84%.

Dr. Shellhaas and her colleagues sought to answer the question, “What would happen if this infant had been treated with ACTH instead of the given medication?” They controlled these comparisons for selection bias by weighting them for various factors that may have increased the odds of using the comparison treatment. They also controlled for potential medical center effects, but did not adjust for dosing regimen.

If the infants who had received nonstandard therapies had instead received ACTH, their response rate would have improved from 5% to 32%, according to this analysis (P less than .01).

In comparisons against other standard treatments, response rates would not have been significantly better if patients had instead received ACTH: 29% for vigabatrin vs. an estimated 37% for ACTH and 46% for oral steroids vs. an estimated 44% for ACTH.

If there was one thing to take away from this, it is that nonstandard therapies do not work nearly as well as ACTH or other standard treatments,” Dr. Shellhaas said. “It is crucial to treat these infants with treatments that are effective.”

Dr. Shellhaas and her associates uncovered certain clinical factors associated with treatment selections. Among infants with unknown infantile spasm etiology, 30% were given nonstandard treatment, whereas 47% received ACTH. Infants who were not already on antiepileptic drugs more often received nonstandard therapies than ACTH (45% vs. 17%).

However, ACTH was still more likely to be given over nonstandard therapies to infants who had hypsarrhythmia (84% vs. 57%) or a normal head circumference (77% vs. 57%).

Dr. Shellhaas reported no relevant financial disclosures. The Pediatric Epilepsy Research Foundation funded the study.

[email protected]

SOURCE: AES 2017 abstract 1.303

WASHINGTON – Standard infantile spasm therapies such as adrenocorticotropic hormone appear to be significantly more effective than nonstandard therapies, according to a prospective study presented at the annual meeting of the American Epilepsy Society.

If infants currently treated with nonstandard therapies switched to adrenocorticotropic hormone (ACTH), there would be an increase of “one additional responder for every four infants with infantile spasms,” according to Renee Shellhaas, MD, a pediatric neurologist at the University of Michigan, Ann Arbor.

Dr. Shellhaas and her colleagues conducted a prospective study of 352 infants recorded to have spasms in the National Infantile Spasms Consortium from 2012 to 2016 and compared successful responses with the use of ACTH and other standard therapies against those with nonstandard therapies. They defined a successful response as a patient who did not take any other medication for infantile spasms for 60 days and had no infantile spasms for 30 days after finishing 30 days of treatment. Infants were split into four treatment arms: ACTH (n = 150), vigabatrin (68), oral steroids (90), and nonstandard therapies (44). Nonstandard therapies included topiramate, levetiracetam, clobazam, zonisamide, ketogenic diet, oxcarbazepine, and phenobarbital.

The proportion of male infants across all arms was 50%-64%, with an average age of 6.2 months in the ACTH group, 5.5 months in the vigabatrin group, 6.7 months in the oral steroids group, and 5.5 months in the nonstandard group. A majority of infants across all arms had hypsarrhythmia on EEG, ranging from 57% to 84%.

Dr. Shellhaas and her colleagues sought to answer the question, “What would happen if this infant had been treated with ACTH instead of the given medication?” They controlled these comparisons for selection bias by weighting them for various factors that may have increased the odds of using the comparison treatment. They also controlled for potential medical center effects, but did not adjust for dosing regimen.

If the infants who had received nonstandard therapies had instead received ACTH, their response rate would have improved from 5% to 32%, according to this analysis (P less than .01).

In comparisons against other standard treatments, response rates would not have been significantly better if patients had instead received ACTH: 29% for vigabatrin vs. an estimated 37% for ACTH and 46% for oral steroids vs. an estimated 44% for ACTH.

If there was one thing to take away from this, it is that nonstandard therapies do not work nearly as well as ACTH or other standard treatments,” Dr. Shellhaas said. “It is crucial to treat these infants with treatments that are effective.”

Dr. Shellhaas and her associates uncovered certain clinical factors associated with treatment selections. Among infants with unknown infantile spasm etiology, 30% were given nonstandard treatment, whereas 47% received ACTH. Infants who were not already on antiepileptic drugs more often received nonstandard therapies than ACTH (45% vs. 17%).

However, ACTH was still more likely to be given over nonstandard therapies to infants who had hypsarrhythmia (84% vs. 57%) or a normal head circumference (77% vs. 57%).

Dr. Shellhaas reported no relevant financial disclosures. The Pediatric Epilepsy Research Foundation funded the study.

[email protected]

SOURCE: AES 2017 abstract 1.303

SAN ANTONIO – Adding trastuzumab to the standard regimen for patients with early-stage breast cancer and low levels of HER2 does not improve outcomes, according to new findings presented at the San Antonio Breast Cancer Symposium.

In a randomized trial of more than 3,000 patients, the 5-year invasive disease–free survival (IDFS) was 89.6% for those who received trastuzumab, compared with 89.2% for those who did not (hazard ratio, 0.98 95% confidence interval, 0.77-1.26, P = .90). Even after stratification for HER2 IHC level, extent of lymph node involvement, or hormone receptor status, the findings remained similar.

Patients in both arms did well, explained lead study author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center. “But the primary endpoint of IDFS was not met and none of the secondary endpoints were met. No trends of efficacy were seen.”

Current guidelines classify a breast cancer as HER2 positive if immunohistochemistry testing shows high levels of HER2 protein, defined as IHC 3+, or increased copies of the HER2 gene in situ hybridization. Adding 1 year of treatment with trastuzumab to standard adjuvant chemotherapy has been found to significantly reduce cancer recurrence and to improve survival for patients with early-stage HER2-positive breast cancer.

However, data from some of the early trastuzumab clinical trials suggested that patients with HER2-low breast cancer may benefit from the HER2-targeted treatment as well.

In 2005, the “stunning” results from the NSABP B-31 trial, of trastuzumab used in HER2+ breast cancer, were presented at the annual meeting of the American Society of Clinical Oncology. The study criteria included having a FISH+ test greater than 2.0 or IHC 3+, and testing was initially performed at a local laboratory site. When testing was conducted by the NSABP, submitted tissue samples showed that 9.7% of patients were not HER2 IHC 3+ or FISH+ greater than 2.0.

There were 174 patients defined as HER2 low, and not HER2 +.

“When the analysis was performed looking at the benefit of using trastuzumab in these patients considered low, it was found that the result was essentially identical, the benefit was equal, and statistically there was no interaction between FISH testing of IHC testing,” said Dr. Fehrenbacher. “These results were bewildering as the hypothesis was that only the HER2 amplified patients would benefit.

Because of these results, the NCI [National Cancer Institute] and the NSABP [National Surgical Adjuvant Breast and Bowel Project] initiated another trial, the N9831, which also found the same benefit in patients who were HER2 low.

About 15% of breast cancers are HER2 positive and another 45% have low levels of HER2, but these patients are not currently treated with adjuvant trastuzumab. Therefore, the current study, the NSABP-B-47, was designed and conducted to see if these early results could be validated in a large, prospective, randomized trial.

The study included 3,270 patients with early-stage breast cancer that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.

The standard regimen consisted of either one of the two chemotherapy regimens, per physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m², cyclophosphamide 600 mg/m²) administered intravenously every 3 weeks for six cycles; the anthracycline regimen is AC followed by weekly paclitaxel (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² administered intravenously either every 3 weeks or every 2 weeks. The same regimen applied to the group that received additional trastuzumab.

The primary endpoint was to determine whether the addition of trastuzumab to chemotherapy improved invasive disease-free survival.

At a median follow-up of 46.1 months, 264 patients had IDFS events. The 5-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.

There was no difference in outcomes for IHC 1+ (HR for IDFS 0.88, 95% CI, 0.63-1.22) or IHC 2+ (HR for IDFS 1.14 95% CI, 0.79-1.65).

“The retrospective outcome difference between local tested HER2 + and center tested HER2-low patients identified in two major adjuvant trials are not readily explained,” said Dr. Fehrenbacher. “There is no benefit with trastuzumab therapy in patients with a FISH ratio of less than 2 and IHC staining intensity of 1+ or 2+.

SOURCE: Fehrenbacher et al. GS1-02

SAN ANTONIO – Adding trastuzumab to the standard regimen for patients with early-stage breast cancer and low levels of HER2 does not improve outcomes, according to new findings presented at the San Antonio Breast Cancer Symposium.

In a randomized trial of more than 3,000 patients, the 5-year invasive disease–free survival (IDFS) was 89.6% for those who received trastuzumab, compared with 89.2% for those who did not (hazard ratio, 0.98 95% confidence interval, 0.77-1.26, P = .90). Even after stratification for HER2 IHC level, extent of lymph node involvement, or hormone receptor status, the findings remained similar.

Patients in both arms did well, explained lead study author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center. “But the primary endpoint of IDFS was not met and none of the secondary endpoints were met. No trends of efficacy were seen.”

Current guidelines classify a breast cancer as HER2 positive if immunohistochemistry testing shows high levels of HER2 protein, defined as IHC 3+, or increased copies of the HER2 gene in situ hybridization. Adding 1 year of treatment with trastuzumab to standard adjuvant chemotherapy has been found to significantly reduce cancer recurrence and to improve survival for patients with early-stage HER2-positive breast cancer.

However, data from some of the early trastuzumab clinical trials suggested that patients with HER2-low breast cancer may benefit from the HER2-targeted treatment as well.

In 2005, the “stunning” results from the NSABP B-31 trial, of trastuzumab used in HER2+ breast cancer, were presented at the annual meeting of the American Society of Clinical Oncology. The study criteria included having a FISH+ test greater than 2.0 or IHC 3+, and testing was initially performed at a local laboratory site. When testing was conducted by the NSABP, submitted tissue samples showed that 9.7% of patients were not HER2 IHC 3+ or FISH+ greater than 2.0.

There were 174 patients defined as HER2 low, and not HER2 +.

“When the analysis was performed looking at the benefit of using trastuzumab in these patients considered low, it was found that the result was essentially identical, the benefit was equal, and statistically there was no interaction between FISH testing of IHC testing,” said Dr. Fehrenbacher. “These results were bewildering as the hypothesis was that only the HER2 amplified patients would benefit.

Because of these results, the NCI [National Cancer Institute] and the NSABP [National Surgical Adjuvant Breast and Bowel Project] initiated another trial, the N9831, which also found the same benefit in patients who were HER2 low.

About 15% of breast cancers are HER2 positive and another 45% have low levels of HER2, but these patients are not currently treated with adjuvant trastuzumab. Therefore, the current study, the NSABP-B-47, was designed and conducted to see if these early results could be validated in a large, prospective, randomized trial.

The study included 3,270 patients with early-stage breast cancer that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.

The standard regimen consisted of either one of the two chemotherapy regimens, per physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m², cyclophosphamide 600 mg/m²) administered intravenously every 3 weeks for six cycles; the anthracycline regimen is AC followed by weekly paclitaxel (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² administered intravenously either every 3 weeks or every 2 weeks. The same regimen applied to the group that received additional trastuzumab.

The primary endpoint was to determine whether the addition of trastuzumab to chemotherapy improved invasive disease-free survival.

At a median follow-up of 46.1 months, 264 patients had IDFS events. The 5-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.

There was no difference in outcomes for IHC 1+ (HR for IDFS 0.88, 95% CI, 0.63-1.22) or IHC 2+ (HR for IDFS 1.14 95% CI, 0.79-1.65).

“The retrospective outcome difference between local tested HER2 + and center tested HER2-low patients identified in two major adjuvant trials are not readily explained,” said Dr. Fehrenbacher. “There is no benefit with trastuzumab therapy in patients with a FISH ratio of less than 2 and IHC staining intensity of 1+ or 2+.

SOURCE: Fehrenbacher et al. GS1-02

SAN ANTONIO – Adding trastuzumab to the standard regimen for patients with early-stage breast cancer and low levels of HER2 does not improve outcomes, according to new findings presented at the San Antonio Breast Cancer Symposium.

In a randomized trial of more than 3,000 patients, the 5-year invasive disease–free survival (IDFS) was 89.6% for those who received trastuzumab, compared with 89.2% for those who did not (hazard ratio, 0.98 95% confidence interval, 0.77-1.26, P = .90). Even after stratification for HER2 IHC level, extent of lymph node involvement, or hormone receptor status, the findings remained similar.

Patients in both arms did well, explained lead study author Louis Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and an oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center. “But the primary endpoint of IDFS was not met and none of the secondary endpoints were met. No trends of efficacy were seen.”

Current guidelines classify a breast cancer as HER2 positive if immunohistochemistry testing shows high levels of HER2 protein, defined as IHC 3+, or increased copies of the HER2 gene in situ hybridization. Adding 1 year of treatment with trastuzumab to standard adjuvant chemotherapy has been found to significantly reduce cancer recurrence and to improve survival for patients with early-stage HER2-positive breast cancer.

However, data from some of the early trastuzumab clinical trials suggested that patients with HER2-low breast cancer may benefit from the HER2-targeted treatment as well.

In 2005, the “stunning” results from the NSABP B-31 trial, of trastuzumab used in HER2+ breast cancer, were presented at the annual meeting of the American Society of Clinical Oncology. The study criteria included having a FISH+ test greater than 2.0 or IHC 3+, and testing was initially performed at a local laboratory site. When testing was conducted by the NSABP, submitted tissue samples showed that 9.7% of patients were not HER2 IHC 3+ or FISH+ greater than 2.0.

There were 174 patients defined as HER2 low, and not HER2 +.

“When the analysis was performed looking at the benefit of using trastuzumab in these patients considered low, it was found that the result was essentially identical, the benefit was equal, and statistically there was no interaction between FISH testing of IHC testing,” said Dr. Fehrenbacher. “These results were bewildering as the hypothesis was that only the HER2 amplified patients would benefit.

Because of these results, the NCI [National Cancer Institute] and the NSABP [National Surgical Adjuvant Breast and Bowel Project] initiated another trial, the N9831, which also found the same benefit in patients who were HER2 low.

About 15% of breast cancers are HER2 positive and another 45% have low levels of HER2, but these patients are not currently treated with adjuvant trastuzumab. Therefore, the current study, the NSABP-B-47, was designed and conducted to see if these early results could be validated in a large, prospective, randomized trial.

The study included 3,270 patients with early-stage breast cancer that was either IHC 1+, IHC 2+, and/or ISH negative in the trial. The patients were randomized 1:1 to standard adjuvant chemotherapy with or without a year of trastuzumab.

The standard regimen consisted of either one of the two chemotherapy regimens, per physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m², cyclophosphamide 600 mg/m²) administered intravenously every 3 weeks for six cycles; the anthracycline regimen is AC followed by weekly paclitaxel (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² administered intravenously either every 3 weeks or every 2 weeks. The same regimen applied to the group that received additional trastuzumab.

The primary endpoint was to determine whether the addition of trastuzumab to chemotherapy improved invasive disease-free survival.

At a median follow-up of 46.1 months, 264 patients had IDFS events. The 5-year estimates for recurrence-free interval, distant recurrence–free interval, and overall survival were not statistically different for patients receiving trastuzumab compared with those not receiving trastuzumab.

There was no difference in outcomes for IHC 1+ (HR for IDFS 0.88, 95% CI, 0.63-1.22) or IHC 2+ (HR for IDFS 1.14 95% CI, 0.79-1.65).

“The retrospective outcome difference between local tested HER2 + and center tested HER2-low patients identified in two major adjuvant trials are not readily explained,” said Dr. Fehrenbacher. “There is no benefit with trastuzumab therapy in patients with a FISH ratio of less than 2 and IHC staining intensity of 1+ or 2+.

SOURCE: Fehrenbacher et al. GS1-02

SAN DIEGO – At first glance, rheumatology may seem like the perfect specialty for physicians who don’t want to be bothered by medical emergencies. But the reality can be more complicated.

As Bharat Kumar, MD, explained to an audience at the annual meeting of the American College of Rheumatology, rheumatologists will at times encounter patients in urgent need of their care due to dire medical conditions. In these situations, he said, there may be no time for careful and cautious diagnostics.

“You have to have an awareness of how you think about things,” advised Dr. Kumar, a rheumatologist/immunologist and clinical assistant professor of internal medicine at the University of Iowa, Iowa City. “During emergencies, you have to rely more on intuition to quickly get at answers.”

Q: When do rheumatologists have to deal with medical emergencies?

A: Rheumatology is considered mostly an outpatient specialty. Most of the time, rheumatologists don’t receive off-hour emergency calls.

But there are conditions in which rheumatologists have to be at the front lines in diagnosing and managing medical emergencies. These range from issues like septic arthritis to scleroderma renal crisis and vasculitis affecting vital organs such as the heart, lungs, and kidneys. These are more common at academic settings, but even rheumatologists in private practice should be aware of these conditions.

Q: How often do rheumatologists come across true emergencies in normal practice?

A: It depends on where the rheumatologist is practicing. In our academic setting, we have to see patients in the hospital several times per week.

Rarer are the emergencies that show up to clinic and require evaluation in the emergency department or hospitalization. Over the past year, that has happened perhaps three times to me.

This is likely much less in the private setting, where patients tend to be less sick and less complicated. But that is no guarantee that an emergency won’t crop up.

Q: What is the scariest emergency situation that you’ve come across?

A: It occurred when I entered a room to see a patient of mine with adult-onset Still’s disease.

She was huddled, shivering, barely answering questions. Her eyes were glazed. Her blood pressure was below 90/60 mm Hg, and her pulse was 130 beats per minute. I was petrified that she was in the midst of a cytokine storm secondary to either hemophagocytic lymphohistiocytosis (HLH) or sepsis. Given the high mortality of both, we immediately called our colleagues in the emergency department and sent her for hospitalization. It turned out that she did have HLH, and we had to pursue intensive immunosuppression to abate that cytokine storm.

It was particularly scary because there is no good way to differentiate between the two conditions, apart from going with clinical intuition.
 

Treating a patient who is potentially septic with immunosuppression is extremely dangerous, and ultimately, we would not have known if our intuition was correct until the infection presented itself.

Fortunately, we were correct. She recovered after 1 week of hospitalization, and we have been following her since then. But it still gives me goosebumps to think, “What if we were wrong?”

Q: Do emergencies in rheumatology tend to appear suddenly or are they more likely to occur because of a long-standing and perhaps untreated condition?

A: While it is true that uncontrolled disease activity can predispose patients to emergencies, other emergencies can occur sporadically and out of the blue.

Many times, an emergency is the first manifestation of disease. The literature is littered with cases of renal crisis being the first manifestation of systemic sclerosis. And internists are often baffled by sudden kidney failure due to previously undiagnosed lupus.

In addition, all rheumatologists have great reverence for septic arthritis and know that it can mimic gout very closely. If a swollen joint is mistaken for gout instead of septic arthritis, this can lead to worsening infection and ultimately, loss of joint function.

Q: What are some potentially dire conditions that may test the diagnostic powers of rheumatologists?

A: Rheumatologists are becoming more aware of HLH. Because it may look clinically indistinguishable from severe infection but needs to be treated with immunosuppression instead of antimicrobial therapy, rheumatologists have to keep it in mind and revisit the diagnosis often in case patients are not improving on the prescribed therapy.

Pulmonary vasculitis is another concerning condition because an otherwise negligible cough can turn into massive pulmonary hemorrhage very quickly.

Q: Do you have tips about dealing with ER doctors, primary doctors and others who may be involved with an emergency?

A: Rheumatologists think differently from other specialists. We are cognitive specialists and think more in the long term. Emergency medicine doctors are more concerned about the short term and how to deal with more immediate issues.

Signposting concerns is essential to optimizing communication. Education of other physicians is also important because more frequently than not, patients with rheumatologic diseases present very differently.

Lastly, there’s a very fine line between advocating for patients and overstepping your bounds as a consultant rheumatologist. Maintaining close collaboration and establishing clear and open lines of communication can prevent this.

Dr. Kumar has no relevant disclosures.

SAN DIEGO – At first glance, rheumatology may seem like the perfect specialty for physicians who don’t want to be bothered by medical emergencies. But the reality can be more complicated.

As Bharat Kumar, MD, explained to an audience at the annual meeting of the American College of Rheumatology, rheumatologists will at times encounter patients in urgent need of their care due to dire medical conditions. In these situations, he said, there may be no time for careful and cautious diagnostics.

“You have to have an awareness of how you think about things,” advised Dr. Kumar, a rheumatologist/immunologist and clinical assistant professor of internal medicine at the University of Iowa, Iowa City. “During emergencies, you have to rely more on intuition to quickly get at answers.”

Q: When do rheumatologists have to deal with medical emergencies?

A: Rheumatology is considered mostly an outpatient specialty. Most of the time, rheumatologists don’t receive off-hour emergency calls.

But there are conditions in which rheumatologists have to be at the front lines in diagnosing and managing medical emergencies. These range from issues like septic arthritis to scleroderma renal crisis and vasculitis affecting vital organs such as the heart, lungs, and kidneys. These are more common at academic settings, but even rheumatologists in private practice should be aware of these conditions.

Q: How often do rheumatologists come across true emergencies in normal practice?

A: It depends on where the rheumatologist is practicing. In our academic setting, we have to see patients in the hospital several times per week.

Rarer are the emergencies that show up to clinic and require evaluation in the emergency department or hospitalization. Over the past year, that has happened perhaps three times to me.

This is likely much less in the private setting, where patients tend to be less sick and less complicated. But that is no guarantee that an emergency won’t crop up.

Q: What is the scariest emergency situation that you’ve come across?

A: It occurred when I entered a room to see a patient of mine with adult-onset Still’s disease.

She was huddled, shivering, barely answering questions. Her eyes were glazed. Her blood pressure was below 90/60 mm Hg, and her pulse was 130 beats per minute. I was petrified that she was in the midst of a cytokine storm secondary to either hemophagocytic lymphohistiocytosis (HLH) or sepsis. Given the high mortality of both, we immediately called our colleagues in the emergency department and sent her for hospitalization. It turned out that she did have HLH, and we had to pursue intensive immunosuppression to abate that cytokine storm.

It was particularly scary because there is no good way to differentiate between the two conditions, apart from going with clinical intuition.
 

Treating a patient who is potentially septic with immunosuppression is extremely dangerous, and ultimately, we would not have known if our intuition was correct until the infection presented itself.

Fortunately, we were correct. She recovered after 1 week of hospitalization, and we have been following her since then. But it still gives me goosebumps to think, “What if we were wrong?”

Q: Do emergencies in rheumatology tend to appear suddenly or are they more likely to occur because of a long-standing and perhaps untreated condition?

A: While it is true that uncontrolled disease activity can predispose patients to emergencies, other emergencies can occur sporadically and out of the blue.

Many times, an emergency is the first manifestation of disease. The literature is littered with cases of renal crisis being the first manifestation of systemic sclerosis. And internists are often baffled by sudden kidney failure due to previously undiagnosed lupus.

In addition, all rheumatologists have great reverence for septic arthritis and know that it can mimic gout very closely. If a swollen joint is mistaken for gout instead of septic arthritis, this can lead to worsening infection and ultimately, loss of joint function.

Q: What are some potentially dire conditions that may test the diagnostic powers of rheumatologists?

A: Rheumatologists are becoming more aware of HLH. Because it may look clinically indistinguishable from severe infection but needs to be treated with immunosuppression instead of antimicrobial therapy, rheumatologists have to keep it in mind and revisit the diagnosis often in case patients are not improving on the prescribed therapy.

Pulmonary vasculitis is another concerning condition because an otherwise negligible cough can turn into massive pulmonary hemorrhage very quickly.

Q: Do you have tips about dealing with ER doctors, primary doctors and others who may be involved with an emergency?

A: Rheumatologists think differently from other specialists. We are cognitive specialists and think more in the long term. Emergency medicine doctors are more concerned about the short term and how to deal with more immediate issues.

Signposting concerns is essential to optimizing communication. Education of other physicians is also important because more frequently than not, patients with rheumatologic diseases present very differently.

Lastly, there’s a very fine line between advocating for patients and overstepping your bounds as a consultant rheumatologist. Maintaining close collaboration and establishing clear and open lines of communication can prevent this.

Dr. Kumar has no relevant disclosures.

SAN DIEGO – At first glance, rheumatology may seem like the perfect specialty for physicians who don’t want to be bothered by medical emergencies. But the reality can be more complicated.

As Bharat Kumar, MD, explained to an audience at the annual meeting of the American College of Rheumatology, rheumatologists will at times encounter patients in urgent need of their care due to dire medical conditions. In these situations, he said, there may be no time for careful and cautious diagnostics.

“You have to have an awareness of how you think about things,” advised Dr. Kumar, a rheumatologist/immunologist and clinical assistant professor of internal medicine at the University of Iowa, Iowa City. “During emergencies, you have to rely more on intuition to quickly get at answers.”

Q: When do rheumatologists have to deal with medical emergencies?

A: Rheumatology is considered mostly an outpatient specialty. Most of the time, rheumatologists don’t receive off-hour emergency calls.

But there are conditions in which rheumatologists have to be at the front lines in diagnosing and managing medical emergencies. These range from issues like septic arthritis to scleroderma renal crisis and vasculitis affecting vital organs such as the heart, lungs, and kidneys. These are more common at academic settings, but even rheumatologists in private practice should be aware of these conditions.

Q: How often do rheumatologists come across true emergencies in normal practice?

A: It depends on where the rheumatologist is practicing. In our academic setting, we have to see patients in the hospital several times per week.

Rarer are the emergencies that show up to clinic and require evaluation in the emergency department or hospitalization. Over the past year, that has happened perhaps three times to me.

This is likely much less in the private setting, where patients tend to be less sick and less complicated. But that is no guarantee that an emergency won’t crop up.

Q: What is the scariest emergency situation that you’ve come across?

A: It occurred when I entered a room to see a patient of mine with adult-onset Still’s disease.

She was huddled, shivering, barely answering questions. Her eyes were glazed. Her blood pressure was below 90/60 mm Hg, and her pulse was 130 beats per minute. I was petrified that she was in the midst of a cytokine storm secondary to either hemophagocytic lymphohistiocytosis (HLH) or sepsis. Given the high mortality of both, we immediately called our colleagues in the emergency department and sent her for hospitalization. It turned out that she did have HLH, and we had to pursue intensive immunosuppression to abate that cytokine storm.

It was particularly scary because there is no good way to differentiate between the two conditions, apart from going with clinical intuition.
 

Treating a patient who is potentially septic with immunosuppression is extremely dangerous, and ultimately, we would not have known if our intuition was correct until the infection presented itself.

Fortunately, we were correct. She recovered after 1 week of hospitalization, and we have been following her since then. But it still gives me goosebumps to think, “What if we were wrong?”

Q: Do emergencies in rheumatology tend to appear suddenly or are they more likely to occur because of a long-standing and perhaps untreated condition?

A: While it is true that uncontrolled disease activity can predispose patients to emergencies, other emergencies can occur sporadically and out of the blue.

Many times, an emergency is the first manifestation of disease. The literature is littered with cases of renal crisis being the first manifestation of systemic sclerosis. And internists are often baffled by sudden kidney failure due to previously undiagnosed lupus.

In addition, all rheumatologists have great reverence for septic arthritis and know that it can mimic gout very closely. If a swollen joint is mistaken for gout instead of septic arthritis, this can lead to worsening infection and ultimately, loss of joint function.

Q: What are some potentially dire conditions that may test the diagnostic powers of rheumatologists?

A: Rheumatologists are becoming more aware of HLH. Because it may look clinically indistinguishable from severe infection but needs to be treated with immunosuppression instead of antimicrobial therapy, rheumatologists have to keep it in mind and revisit the diagnosis often in case patients are not improving on the prescribed therapy.

Pulmonary vasculitis is another concerning condition because an otherwise negligible cough can turn into massive pulmonary hemorrhage very quickly.

Q: Do you have tips about dealing with ER doctors, primary doctors and others who may be involved with an emergency?

A: Rheumatologists think differently from other specialists. We are cognitive specialists and think more in the long term. Emergency medicine doctors are more concerned about the short term and how to deal with more immediate issues.

Signposting concerns is essential to optimizing communication. Education of other physicians is also important because more frequently than not, patients with rheumatologic diseases present very differently.

Lastly, there’s a very fine line between advocating for patients and overstepping your bounds as a consultant rheumatologist. Maintaining close collaboration and establishing clear and open lines of communication can prevent this.

Dr. Kumar has no relevant disclosures.

Two medicines used to treat opioid use disorder—buprenorphine/naloxone (Suboxone) and extended-release naltrexone (Vivitrol)—have similar outcomes if the patient adheres to the treatment, according to a 24-week study of 570 opioid-dependent adults.

The researchers expected that it would be more difficult to initiate treatment with naltrexone because it requires full detoxification, and patients often drop out of the process. And indeed, fewer patients successfully initiated naltrexone, compared with buprenorphine/naloxone (72% vs 94%). The 24-week relapse rates were slightly higher for naltrexone: 65%, compared with 57% for buprenorphine/naloxone, mainly due to early relapse in the naltrexone group.

But among the 474 patients who successfully started on medication, the relapse rates were similar: 52% for naltrexone vs 56% for buprenorphine/naloxone.

Other outcomes among patients who began treatment—days abstinent, negative urine tests, and time to relapse—generally favored buprenorphine/naloxone in the full group, the researchers say. When only those who initiated treatment were considered, the outcomes slightly favored naltrexone.

During the study, 5 people had fatal overdoses: 3 in the buprenorphine/naloxone group and 2 in the naltrexone group. However, overall overdose rates, including nonfatal overdose, were low compared with what would be expected in this population, the researchers say. Their findings “strongly support” the conclusion that medication protects against overdose.

“Studies show that people with opioid dependence who follow detoxification with no medication are very likely to return to drug use,” said Nora Volkow, MD, director of the National Institute on Drug Abuse. “Yet many treatment programs have been slow to accept medications that have proven to be safe and effective. These findings should encourage clinicians to use medication protocols.”

Two medicines used to treat opioid use disorder—buprenorphine/naloxone (Suboxone) and extended-release naltrexone (Vivitrol)—have similar outcomes if the patient adheres to the treatment, according to a 24-week study of 570 opioid-dependent adults.

The researchers expected that it would be more difficult to initiate treatment with naltrexone because it requires full detoxification, and patients often drop out of the process. And indeed, fewer patients successfully initiated naltrexone, compared with buprenorphine/naloxone (72% vs 94%). The 24-week relapse rates were slightly higher for naltrexone: 65%, compared with 57% for buprenorphine/naloxone, mainly due to early relapse in the naltrexone group.

But among the 474 patients who successfully started on medication, the relapse rates were similar: 52% for naltrexone vs 56% for buprenorphine/naloxone.

Other outcomes among patients who began treatment—days abstinent, negative urine tests, and time to relapse—generally favored buprenorphine/naloxone in the full group, the researchers say. When only those who initiated treatment were considered, the outcomes slightly favored naltrexone.

During the study, 5 people had fatal overdoses: 3 in the buprenorphine/naloxone group and 2 in the naltrexone group. However, overall overdose rates, including nonfatal overdose, were low compared with what would be expected in this population, the researchers say. Their findings “strongly support” the conclusion that medication protects against overdose.

“Studies show that people with opioid dependence who follow detoxification with no medication are very likely to return to drug use,” said Nora Volkow, MD, director of the National Institute on Drug Abuse. “Yet many treatment programs have been slow to accept medications that have proven to be safe and effective. These findings should encourage clinicians to use medication protocols.”

Two medicines used to treat opioid use disorder—buprenorphine/naloxone (Suboxone) and extended-release naltrexone (Vivitrol)—have similar outcomes if the patient adheres to the treatment, according to a 24-week study of 570 opioid-dependent adults.

The researchers expected that it would be more difficult to initiate treatment with naltrexone because it requires full detoxification, and patients often drop out of the process. And indeed, fewer patients successfully initiated naltrexone, compared with buprenorphine/naloxone (72% vs 94%). The 24-week relapse rates were slightly higher for naltrexone: 65%, compared with 57% for buprenorphine/naloxone, mainly due to early relapse in the naltrexone group.

But among the 474 patients who successfully started on medication, the relapse rates were similar: 52% for naltrexone vs 56% for buprenorphine/naloxone.

Other outcomes among patients who began treatment—days abstinent, negative urine tests, and time to relapse—generally favored buprenorphine/naloxone in the full group, the researchers say. When only those who initiated treatment were considered, the outcomes slightly favored naltrexone.

During the study, 5 people had fatal overdoses: 3 in the buprenorphine/naloxone group and 2 in the naltrexone group. However, overall overdose rates, including nonfatal overdose, were low compared with what would be expected in this population, the researchers say. Their findings “strongly support” the conclusion that medication protects against overdose.

“Studies show that people with opioid dependence who follow detoxification with no medication are very likely to return to drug use,” said Nora Volkow, MD, director of the National Institute on Drug Abuse. “Yet many treatment programs have been slow to accept medications that have proven to be safe and effective. These findings should encourage clinicians to use medication protocols.”

A 51-year-old Hispanic man presents for evaluation of a lesion he was born with. It grew as he did and was never more than a cosmetic problem until recently, when it became enlarged and sensitive. His family members convinced him to have it evaluated by primary care, who referred him to dermatology.

The patient denies any health problems other than type 2 diabetes, which is adequately controlled. His dark skin almost always tans, rather than burns, with sun exposure.

EXAMINATION

The lesion is hard to miss, measuring 1.8 cm x 5.5 mm and located prominently in the upper left nasolabial fold. It is quite firm, brownish red, hair-bearing, and round, with fine mammilations on the surface. It sits on a base only slightly smaller than the lesion’s surface. The rest of the patient’s skin is unremarkable.

Given that the lesion has changed and is quite sizeable, it is excised with a curving elliptiform incision along relaxed skin tension lines, paralleling the nasolabial fold, and sent for pathologic examination.

What is the diagnosis?

The pathology report confirmed the benign nature of this congenital melanocytic nevus (CMN). CMNs are hamartomatous lesions that form when collections of melanocytes (normal pigment cells) congregate in one location. These cells migrate during the embryonal stage of development—but some never make it to their final destination.

While CMNs are almost always benign, the history of change in this case made excision compelling. Given the lesion’s likely extension well under the surface of the skin, a shave removal would not suffice—and would leave a noticeable scar.

Despite their low potential for malignancy, CMNs—like any lesion removed from the body—must be sent for pathologic examination. The general rule is: the larger the congenital lesion, the greater the malignant potential.

Remember, too, that not all skin cancers are melanomas. Virtually any cell in the skin (sweat glands, neural tissue, sebaceous glands, smooth muscle, and even hair follicles) can undergo malignant transformation, so microscopic examination is mandatory for all removed lesions, except tiny tags or warts.

Interestingly, CMNs are more common on patients with lighter skin. However, besides the case patient, there were also several family members reporting a history of similar lesions. They were all thrilled with the patient’s cosmetic outcome—and more so with the benign report.

TAKE-HOME LEARNING POINTS

• Congenital melanocytic nevi (CMNs) are collections of melanocytes in one area.
• CMNs have little malignant potential, but morphology (eg, color, shape, symptoms) or size may dictate the need for removal or biopsy.
• Deep shave or excision are the best options for removal; patient age, lesion location, potential for scarring, and surgical ability of the provider influence choice.
• Since melanocytes can end up in other extracutaneous locations, primary melanomas can develop almost anywhere—including the lungs, the gut, or even the eyes.

A 51-year-old Hispanic man presents for evaluation of a lesion he was born with. It grew as he did and was never more than a cosmetic problem until recently, when it became enlarged and sensitive. His family members convinced him to have it evaluated by primary care, who referred him to dermatology.

The patient denies any health problems other than type 2 diabetes, which is adequately controlled. His dark skin almost always tans, rather than burns, with sun exposure.

EXAMINATION

The lesion is hard to miss, measuring 1.8 cm x 5.5 mm and located prominently in the upper left nasolabial fold. It is quite firm, brownish red, hair-bearing, and round, with fine mammilations on the surface. It sits on a base only slightly smaller than the lesion’s surface. The rest of the patient’s skin is unremarkable.

Given that the lesion has changed and is quite sizeable, it is excised with a curving elliptiform incision along relaxed skin tension lines, paralleling the nasolabial fold, and sent for pathologic examination.

What is the diagnosis?

The pathology report confirmed the benign nature of this congenital melanocytic nevus (CMN). CMNs are hamartomatous lesions that form when collections of melanocytes (normal pigment cells) congregate in one location. These cells migrate during the embryonal stage of development—but some never make it to their final destination.

While CMNs are almost always benign, the history of change in this case made excision compelling. Given the lesion’s likely extension well under the surface of the skin, a shave removal would not suffice—and would leave a noticeable scar.

Despite their low potential for malignancy, CMNs—like any lesion removed from the body—must be sent for pathologic examination. The general rule is: the larger the congenital lesion, the greater the malignant potential.

Remember, too, that not all skin cancers are melanomas. Virtually any cell in the skin (sweat glands, neural tissue, sebaceous glands, smooth muscle, and even hair follicles) can undergo malignant transformation, so microscopic examination is mandatory for all removed lesions, except tiny tags or warts.

Interestingly, CMNs are more common on patients with lighter skin. However, besides the case patient, there were also several family members reporting a history of similar lesions. They were all thrilled with the patient’s cosmetic outcome—and more so with the benign report.

TAKE-HOME LEARNING POINTS

• Congenital melanocytic nevi (CMNs) are collections of melanocytes in one area.
• CMNs have little malignant potential, but morphology (eg, color, shape, symptoms) or size may dictate the need for removal or biopsy.
• Deep shave or excision are the best options for removal; patient age, lesion location, potential for scarring, and surgical ability of the provider influence choice.
• Since melanocytes can end up in other extracutaneous locations, primary melanomas can develop almost anywhere—including the lungs, the gut, or even the eyes.

A 51-year-old Hispanic man presents for evaluation of a lesion he was born with. It grew as he did and was never more than a cosmetic problem until recently, when it became enlarged and sensitive. His family members convinced him to have it evaluated by primary care, who referred him to dermatology.

The patient denies any health problems other than type 2 diabetes, which is adequately controlled. His dark skin almost always tans, rather than burns, with sun exposure.

EXAMINATION

The lesion is hard to miss, measuring 1.8 cm x 5.5 mm and located prominently in the upper left nasolabial fold. It is quite firm, brownish red, hair-bearing, and round, with fine mammilations on the surface. It sits on a base only slightly smaller than the lesion’s surface. The rest of the patient’s skin is unremarkable.

Given that the lesion has changed and is quite sizeable, it is excised with a curving elliptiform incision along relaxed skin tension lines, paralleling the nasolabial fold, and sent for pathologic examination.

What is the diagnosis?

The pathology report confirmed the benign nature of this congenital melanocytic nevus (CMN). CMNs are hamartomatous lesions that form when collections of melanocytes (normal pigment cells) congregate in one location. These cells migrate during the embryonal stage of development—but some never make it to their final destination.

While CMNs are almost always benign, the history of change in this case made excision compelling. Given the lesion’s likely extension well under the surface of the skin, a shave removal would not suffice—and would leave a noticeable scar.

Despite their low potential for malignancy, CMNs—like any lesion removed from the body—must be sent for pathologic examination. The general rule is: the larger the congenital lesion, the greater the malignant potential.

Remember, too, that not all skin cancers are melanomas. Virtually any cell in the skin (sweat glands, neural tissue, sebaceous glands, smooth muscle, and even hair follicles) can undergo malignant transformation, so microscopic examination is mandatory for all removed lesions, except tiny tags or warts.

Interestingly, CMNs are more common on patients with lighter skin. However, besides the case patient, there were also several family members reporting a history of similar lesions. They were all thrilled with the patient’s cosmetic outcome—and more so with the benign report.

TAKE-HOME LEARNING POINTS

• Congenital melanocytic nevi (CMNs) are collections of melanocytes in one area.
• CMNs have little malignant potential, but morphology (eg, color, shape, symptoms) or size may dictate the need for removal or biopsy.
• Deep shave or excision are the best options for removal; patient age, lesion location, potential for scarring, and surgical ability of the provider influence choice.
• Since melanocytes can end up in other extracutaneous locations, primary melanomas can develop almost anywhere—including the lungs, the gut, or even the eyes.

Image by Spencer Phillips

The gene therapy SPK-9001 has produced positive results in a phase 1/2 trial of adults with hemophilia B, according to researchers.

SPK-9001 produced sustained factor IX (FIX) activity and allowed all 10 patients in this study to stop FIX prophylaxis.

Eight patients had no further FIX treatment after SPK-9001, and 9 patients had 0 bleeds.

There were no serious adverse events, and none of the patients had thrombotic events or developed FIX inhibitors.

“A one-time therapy sufficient to prevent bleeding without further medical intervention is the ideal treatment goal for patients with hemophilia,” said Lindsey A. George, MD, a hematologist at Children’s Hospital of Philadelphia in Pennsylvania.

“This cohort of 10 patients all safely experienced sustained clinical benefit after one infusion.”

Dr George and her colleagues reported these results in NEJM. The trial was sponsored by Spark Therapeutics and Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human FIX gene enabling endogenous production of FIX.

The researchers tested SPK-9001 in 10 males with hemophilia B.

With a cumulative follow-up of 492 weeks, the mean steady-state FIX activity was 34% of normal (range, 14% to 81%) after a single administration of SPK-9001.

The annualized bleeding rate was reduced 97%, from a mean rate of 11.1 events per year before SPK-9001 administration to 0.4 events per year after (P=0.02).

Nine patients had 0 bleeds after SPK-9001, and 1 patient had 4 bleeds.

Use of FIX treatment was reduced 99% during this study, from a mean dose of 2908 IU/kg (range, 0 to 8090) before SPK-9001 to a mean dose of 49.3 IU/kg (range, 0 to 376) after SPK-9001 (P=0.004).

Two patients did receive FIX treatment after SPK-9001, but none of the patients received FIX prophylaxis.

The researchers noted that the patient who required FIX treatment for bleeding (4 events) had significant baseline joint damage. However, this patient still used 91% less FIX than before he received SPK-9001.

There were a total of 40 adverse events in this study, but none were serious. There were no deaths, no thrombotic events, and no cases of inhibitor development.

The only adverse events thought to be related to SPK-9001 were asymptomatic and transient increases in liver enzymes in 2 patients. These events resolved with a tapering dose of oral corticosteroids.

“People who live with hemophilia face a life-long need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said study author Katherine High, MD, president and head of Research and Development at Spark Therapeutics.

“The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

Image by Spencer Phillips

The gene therapy SPK-9001 has produced positive results in a phase 1/2 trial of adults with hemophilia B, according to researchers.

SPK-9001 produced sustained factor IX (FIX) activity and allowed all 10 patients in this study to stop FIX prophylaxis.

Eight patients had no further FIX treatment after SPK-9001, and 9 patients had 0 bleeds.

There were no serious adverse events, and none of the patients had thrombotic events or developed FIX inhibitors.

“A one-time therapy sufficient to prevent bleeding without further medical intervention is the ideal treatment goal for patients with hemophilia,” said Lindsey A. George, MD, a hematologist at Children’s Hospital of Philadelphia in Pennsylvania.

“This cohort of 10 patients all safely experienced sustained clinical benefit after one infusion.”

Dr George and her colleagues reported these results in NEJM. The trial was sponsored by Spark Therapeutics and Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human FIX gene enabling endogenous production of FIX.

The researchers tested SPK-9001 in 10 males with hemophilia B.

With a cumulative follow-up of 492 weeks, the mean steady-state FIX activity was 34% of normal (range, 14% to 81%) after a single administration of SPK-9001.

The annualized bleeding rate was reduced 97%, from a mean rate of 11.1 events per year before SPK-9001 administration to 0.4 events per year after (P=0.02).

Nine patients had 0 bleeds after SPK-9001, and 1 patient had 4 bleeds.

Use of FIX treatment was reduced 99% during this study, from a mean dose of 2908 IU/kg (range, 0 to 8090) before SPK-9001 to a mean dose of 49.3 IU/kg (range, 0 to 376) after SPK-9001 (P=0.004).

Two patients did receive FIX treatment after SPK-9001, but none of the patients received FIX prophylaxis.

The researchers noted that the patient who required FIX treatment for bleeding (4 events) had significant baseline joint damage. However, this patient still used 91% less FIX than before he received SPK-9001.

There were a total of 40 adverse events in this study, but none were serious. There were no deaths, no thrombotic events, and no cases of inhibitor development.

The only adverse events thought to be related to SPK-9001 were asymptomatic and transient increases in liver enzymes in 2 patients. These events resolved with a tapering dose of oral corticosteroids.

“People who live with hemophilia face a life-long need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said study author Katherine High, MD, president and head of Research and Development at Spark Therapeutics.

“The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

Image by Spencer Phillips

The gene therapy SPK-9001 has produced positive results in a phase 1/2 trial of adults with hemophilia B, according to researchers.

SPK-9001 produced sustained factor IX (FIX) activity and allowed all 10 patients in this study to stop FIX prophylaxis.

Eight patients had no further FIX treatment after SPK-9001, and 9 patients had 0 bleeds.

There were no serious adverse events, and none of the patients had thrombotic events or developed FIX inhibitors.

“A one-time therapy sufficient to prevent bleeding without further medical intervention is the ideal treatment goal for patients with hemophilia,” said Lindsey A. George, MD, a hematologist at Children’s Hospital of Philadelphia in Pennsylvania.

“This cohort of 10 patients all safely experienced sustained clinical benefit after one infusion.”

Dr George and her colleagues reported these results in NEJM. The trial was sponsored by Spark Therapeutics and Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human FIX gene enabling endogenous production of FIX.

The researchers tested SPK-9001 in 10 males with hemophilia B.

With a cumulative follow-up of 492 weeks, the mean steady-state FIX activity was 34% of normal (range, 14% to 81%) after a single administration of SPK-9001.

The annualized bleeding rate was reduced 97%, from a mean rate of 11.1 events per year before SPK-9001 administration to 0.4 events per year after (P=0.02).

Nine patients had 0 bleeds after SPK-9001, and 1 patient had 4 bleeds.

Use of FIX treatment was reduced 99% during this study, from a mean dose of 2908 IU/kg (range, 0 to 8090) before SPK-9001 to a mean dose of 49.3 IU/kg (range, 0 to 376) after SPK-9001 (P=0.004).

Two patients did receive FIX treatment after SPK-9001, but none of the patients received FIX prophylaxis.

The researchers noted that the patient who required FIX treatment for bleeding (4 events) had significant baseline joint damage. However, this patient still used 91% less FIX than before he received SPK-9001.

There were a total of 40 adverse events in this study, but none were serious. There were no deaths, no thrombotic events, and no cases of inhibitor development.

The only adverse events thought to be related to SPK-9001 were asymptomatic and transient increases in liver enzymes in 2 patients. These events resolved with a tapering dose of oral corticosteroids.

“People who live with hemophilia face a life-long need for vigilant monitoring and recurrent factor concentrate infusions to prevent spontaneous, potentially life-threatening bleeds and to protect their joints,” said study author Katherine High, MD, president and head of Research and Development at Spark Therapeutics.

“The data suggest a one-time infusion of SPK-9001 has the potential to safely sustain factor IX coagulant activity level that may result in the termination of baseline prophylaxis factor infusions, significantly reduce bleeding, and nearly eliminate the need for exogenous factor IX concentrate infusions.”

Photo from Business Wire

The US Food and Drug Administration (FDA) has lifted the partial clinical hold placed on 2 trials of the PD-1 immune checkpoint inhibitor nivolumab (Opdivo).

In these trials, CheckMate-039 (CA209 -039) and CA204142, researchers are investigating nivolumab-based combinations in patients with relapsed or refractory multiple myeloma (MM).

The partial clinical hold on these trials was a result of risks identified in studies involving another anti-PD-1 agent, pembrolizumab.

Data from the pembrolizumab trials suggested that risks outweigh benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.

In addition, there could be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.

Therefore, the FDA placed a partial hold on the following nivolumab trials:

• CheckMate-602: A randomized, phase 3 trial of combinations of nivolumab, elotuzumab, pomalidomide, and dexamethasone in relapsed and refractory MM
• CheckMate-039: A phase 1 study intended to establish the tolerability of nivolumab and the combination of nivolumab and daratumumab, with or without pomalidomide and dexamethasone, in patients with relapsed or refractory MM
• CA204142: A phase 2 study of elotuzumab in combination with pomalidomide and low-dose dexamethasone, and in combination with nivolumab, in patients with MM who relapsed after or were refractory to prior treatment with lenalidomide.

After consulting with Bristol-Myers Squibb, the FDA decided to lift the hold on CheckMate-039 (CA209 -039) and CA204142. These trials will continue with amended protocols.

The third trial, CheckMate-602, remains on partial clinical hold. Bristol-Myers Squibb said it is continuing to work with the FDA to determine next steps for this trial.

CheckMate-602 is not enrolling new patients. However, patients who are experiencing clinical benefit are continuing to receive treatment.

Photo from Business Wire

The US Food and Drug Administration (FDA) has lifted the partial clinical hold placed on 2 trials of the PD-1 immune checkpoint inhibitor nivolumab (Opdivo).

In these trials, CheckMate-039 (CA209 -039) and CA204142, researchers are investigating nivolumab-based combinations in patients with relapsed or refractory multiple myeloma (MM).

The partial clinical hold on these trials was a result of risks identified in studies involving another anti-PD-1 agent, pembrolizumab.

Data from the pembrolizumab trials suggested that risks outweigh benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.

In addition, there could be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.

Therefore, the FDA placed a partial hold on the following nivolumab trials:

• CheckMate-602: A randomized, phase 3 trial of combinations of nivolumab, elotuzumab, pomalidomide, and dexamethasone in relapsed and refractory MM
• CheckMate-039: A phase 1 study intended to establish the tolerability of nivolumab and the combination of nivolumab and daratumumab, with or without pomalidomide and dexamethasone, in patients with relapsed or refractory MM
• CA204142: A phase 2 study of elotuzumab in combination with pomalidomide and low-dose dexamethasone, and in combination with nivolumab, in patients with MM who relapsed after or were refractory to prior treatment with lenalidomide.

After consulting with Bristol-Myers Squibb, the FDA decided to lift the hold on CheckMate-039 (CA209 -039) and CA204142. These trials will continue with amended protocols.

The third trial, CheckMate-602, remains on partial clinical hold. Bristol-Myers Squibb said it is continuing to work with the FDA to determine next steps for this trial.

CheckMate-602 is not enrolling new patients. However, patients who are experiencing clinical benefit are continuing to receive treatment.

Photo from Business Wire

The US Food and Drug Administration (FDA) has lifted the partial clinical hold placed on 2 trials of the PD-1 immune checkpoint inhibitor nivolumab (Opdivo).

In these trials, CheckMate-039 (CA209 -039) and CA204142, researchers are investigating nivolumab-based combinations in patients with relapsed or refractory multiple myeloma (MM).

The partial clinical hold on these trials was a result of risks identified in studies involving another anti-PD-1 agent, pembrolizumab.

Data from the pembrolizumab trials suggested that risks outweigh benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.

In addition, there could be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.

Therefore, the FDA placed a partial hold on the following nivolumab trials:

• CheckMate-602: A randomized, phase 3 trial of combinations of nivolumab, elotuzumab, pomalidomide, and dexamethasone in relapsed and refractory MM
• CheckMate-039: A phase 1 study intended to establish the tolerability of nivolumab and the combination of nivolumab and daratumumab, with or without pomalidomide and dexamethasone, in patients with relapsed or refractory MM
• CA204142: A phase 2 study of elotuzumab in combination with pomalidomide and low-dose dexamethasone, and in combination with nivolumab, in patients with MM who relapsed after or were refractory to prior treatment with lenalidomide.

After consulting with Bristol-Myers Squibb, the FDA decided to lift the hold on CheckMate-039 (CA209 -039) and CA204142. These trials will continue with amended protocols.

The third trial, CheckMate-602, remains on partial clinical hold. Bristol-Myers Squibb said it is continuing to work with the FDA to determine next steps for this trial.

CheckMate-602 is not enrolling new patients. However, patients who are experiencing clinical benefit are continuing to receive treatment.

Photo by William Weinert

Bio-Rad Laboratories, Inc., has launched the QXDx BCR-ABL %IS Kit, a digital polymerase chain reaction (PCR) test that can monitor molecular response to therapy in patients with chronic myeloid leukemia (CML).

The kit has a CE-IVD mark and is available for in vitro diagnostic use in Europe, Hong Kong, and New Zealand.

The QXDx BCR-ABL %IS Kit uses Bio-Rad’s Droplet Digital PCR (ddPCR) technology to provide an absolute measure of BCR-ABL transcripts.

The kit measures BCR-ABL1 and ABL1 chromosomal transcripts in total RNA from whole blood of t(9;22)-positive CML patients expressing BCR-ABL1 fusion transcripts type e13a2 and/or e14a2.

The QXDx BCR-ABL %IS Kit measures the e13a2 and/or e14a2 transcripts of BCR-ABL1, normalized to the ABL1 endogenous control. The kit does not differentiate between e13a2 and e14a2 transcripts and does not monitor other rare fusion transcripts resulting from t(9;22).

The kit’s results are reported as percent reduction from a baseline of 100% on the International Scale (%IS) and on a log molecular reduction (MR) scale.

The kit is able to detect deep molecular response values of MR 4.7 (%IS 0.002) or MR 5.0 (%IS 0.001) in 2- or 4-well formats. This exceeds the typical limitations of reverse transcription quantitative PCR-based tests that are reliable down to MR 4.5 (%IS 0.0032).

Bio-Rad says the QXDx BCR-ABL %IS Kit delivers absolute quantitation, which eliminates the need for standard curves and minimizes variation between samples. The kit also provides scalable throughput, allowing for testing of 8 to 48 samples per run.

The QXDx BCR-ABL %IS Kit can be used with Bio-Rad’s QX200 AutoDG ddPCR Dx System or with the QX200 ddPCR Dx System. The QXDx BCR-ABL %IS Kit uses QuantaSoft Software v1.7 for data acquisition and output.

Photo by William Weinert

Bio-Rad Laboratories, Inc., has launched the QXDx BCR-ABL %IS Kit, a digital polymerase chain reaction (PCR) test that can monitor molecular response to therapy in patients with chronic myeloid leukemia (CML).

The kit has a CE-IVD mark and is available for in vitro diagnostic use in Europe, Hong Kong, and New Zealand.

The QXDx BCR-ABL %IS Kit uses Bio-Rad’s Droplet Digital PCR (ddPCR) technology to provide an absolute measure of BCR-ABL transcripts.

The kit measures BCR-ABL1 and ABL1 chromosomal transcripts in total RNA from whole blood of t(9;22)-positive CML patients expressing BCR-ABL1 fusion transcripts type e13a2 and/or e14a2.

The QXDx BCR-ABL %IS Kit measures the e13a2 and/or e14a2 transcripts of BCR-ABL1, normalized to the ABL1 endogenous control. The kit does not differentiate between e13a2 and e14a2 transcripts and does not monitor other rare fusion transcripts resulting from t(9;22).

The kit’s results are reported as percent reduction from a baseline of 100% on the International Scale (%IS) and on a log molecular reduction (MR) scale.

The kit is able to detect deep molecular response values of MR 4.7 (%IS 0.002) or MR 5.0 (%IS 0.001) in 2- or 4-well formats. This exceeds the typical limitations of reverse transcription quantitative PCR-based tests that are reliable down to MR 4.5 (%IS 0.0032).

Bio-Rad says the QXDx BCR-ABL %IS Kit delivers absolute quantitation, which eliminates the need for standard curves and minimizes variation between samples. The kit also provides scalable throughput, allowing for testing of 8 to 48 samples per run.

The QXDx BCR-ABL %IS Kit can be used with Bio-Rad’s QX200 AutoDG ddPCR Dx System or with the QX200 ddPCR Dx System. The QXDx BCR-ABL %IS Kit uses QuantaSoft Software v1.7 for data acquisition and output.

Photo by William Weinert

Bio-Rad Laboratories, Inc., has launched the QXDx BCR-ABL %IS Kit, a digital polymerase chain reaction (PCR) test that can monitor molecular response to therapy in patients with chronic myeloid leukemia (CML).

The kit has a CE-IVD mark and is available for in vitro diagnostic use in Europe, Hong Kong, and New Zealand.

The QXDx BCR-ABL %IS Kit uses Bio-Rad’s Droplet Digital PCR (ddPCR) technology to provide an absolute measure of BCR-ABL transcripts.

The kit measures BCR-ABL1 and ABL1 chromosomal transcripts in total RNA from whole blood of t(9;22)-positive CML patients expressing BCR-ABL1 fusion transcripts type e13a2 and/or e14a2.

The QXDx BCR-ABL %IS Kit measures the e13a2 and/or e14a2 transcripts of BCR-ABL1, normalized to the ABL1 endogenous control. The kit does not differentiate between e13a2 and e14a2 transcripts and does not monitor other rare fusion transcripts resulting from t(9;22).

The kit’s results are reported as percent reduction from a baseline of 100% on the International Scale (%IS) and on a log molecular reduction (MR) scale.

The kit is able to detect deep molecular response values of MR 4.7 (%IS 0.002) or MR 5.0 (%IS 0.001) in 2- or 4-well formats. This exceeds the typical limitations of reverse transcription quantitative PCR-based tests that are reliable down to MR 4.5 (%IS 0.0032).

Bio-Rad says the QXDx BCR-ABL %IS Kit delivers absolute quantitation, which eliminates the need for standard curves and minimizes variation between samples. The kit also provides scalable throughput, allowing for testing of 8 to 48 samples per run.

The QXDx BCR-ABL %IS Kit can be used with Bio-Rad’s QX200 AutoDG ddPCR Dx System or with the QX200 ddPCR Dx System. The QXDx BCR-ABL %IS Kit uses QuantaSoft Software v1.7 for data acquisition and output.

Based on the dark velvety skin on the patient’s neck, the FP diagnosed acanthosis nigricans accompanied by multiple skin tags (acrochordons). The patient told the physician that he wanted to have the skin tags removed and the darkened skin treated. Because both conditions are associated with obesity and diabetes, the FP recommended that the patient increase his weight loss efforts through improved diet and increased exercise.

The FP also explained that treatment options for the skin tags included cryotherapy, snip excisions, and electrosurgery. The patient did not want to wait for the skin tags to fall off after cryotherapy or electrosurgery, so he chose snip excisions for immediate results. The skin tags were pedunculated with narrow stalks, so the snip excisions were performed without anesthesia. Aluminum chloride was applied to stop the bleeding on some of the skin tags. The patient noted some stinging, but tolerated the treatment well.

For the acanthosis nigricans, the FP explained that there are no highly effective treatments. In addition to recommending weight loss, the FP prescribed topical tretinoin cream 0.025% to be applied to the darkened skin before bed (only after the cuts from the skin tag removals had healed). The FP told the patient that the treatment might be only partially beneficial (or might not work at all). Other treatment options for acanthosis nigricans (with limited effectiveness) include keratolytic agents (eg, salicylic acid, ammonium lactate) and topical vitamin D analogs. At follow-up one month later, the patient had not yet noticed any changes to the acanthosis nigricans, but he was satisfied with the results of the skin tag removal.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith AM. Skin tags. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 922-925.

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

Based on the dark velvety skin on the patient’s neck, the FP diagnosed acanthosis nigricans accompanied by multiple skin tags (acrochordons). The patient told the physician that he wanted to have the skin tags removed and the darkened skin treated. Because both conditions are associated with obesity and diabetes, the FP recommended that the patient increase his weight loss efforts through improved diet and increased exercise.

The FP also explained that treatment options for the skin tags included cryotherapy, snip excisions, and electrosurgery. The patient did not want to wait for the skin tags to fall off after cryotherapy or electrosurgery, so he chose snip excisions for immediate results. The skin tags were pedunculated with narrow stalks, so the snip excisions were performed without anesthesia. Aluminum chloride was applied to stop the bleeding on some of the skin tags. The patient noted some stinging, but tolerated the treatment well.

For the acanthosis nigricans, the FP explained that there are no highly effective treatments. In addition to recommending weight loss, the FP prescribed topical tretinoin cream 0.025% to be applied to the darkened skin before bed (only after the cuts from the skin tag removals had healed). The FP told the patient that the treatment might be only partially beneficial (or might not work at all). Other treatment options for acanthosis nigricans (with limited effectiveness) include keratolytic agents (eg, salicylic acid, ammonium lactate) and topical vitamin D analogs. At follow-up one month later, the patient had not yet noticed any changes to the acanthosis nigricans, but he was satisfied with the results of the skin tag removal.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith AM. Skin tags. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 922-925.

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

Based on the dark velvety skin on the patient’s neck, the FP diagnosed acanthosis nigricans accompanied by multiple skin tags (acrochordons). The patient told the physician that he wanted to have the skin tags removed and the darkened skin treated. Because both conditions are associated with obesity and diabetes, the FP recommended that the patient increase his weight loss efforts through improved diet and increased exercise.

The FP also explained that treatment options for the skin tags included cryotherapy, snip excisions, and electrosurgery. The patient did not want to wait for the skin tags to fall off after cryotherapy or electrosurgery, so he chose snip excisions for immediate results. The skin tags were pedunculated with narrow stalks, so the snip excisions were performed without anesthesia. Aluminum chloride was applied to stop the bleeding on some of the skin tags. The patient noted some stinging, but tolerated the treatment well.

For the acanthosis nigricans, the FP explained that there are no highly effective treatments. In addition to recommending weight loss, the FP prescribed topical tretinoin cream 0.025% to be applied to the darkened skin before bed (only after the cuts from the skin tag removals had healed). The FP told the patient that the treatment might be only partially beneficial (or might not work at all). Other treatment options for acanthosis nigricans (with limited effectiveness) include keratolytic agents (eg, salicylic acid, ammonium lactate) and topical vitamin D analogs. At follow-up one month later, the patient had not yet noticed any changes to the acanthosis nigricans, but he was satisfied with the results of the skin tag removal.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith AM. Skin tags. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 922-925.

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