CHICAGO – The novel combination of everolimus, letrozole, and metformin was associated with improved clinical benefit and objective response rates, compared with everolimus and letrozole without metformin in patients with advanced or recurrent, previously treated endometrioid endometrial cancer (EEC) in an ongoing open-label, single-arm, prospective phase II study.

Frontline Medical News

In 49 patients with an evaluable response to the combination therapy, 29 (60%) derived clinical benefit – defined as complete response, partial response, or stable disease confirmed at 8 weeks by RECIST 1.1, Dr. Pamela T. Soliman reported at the annual meeting of the American Society of Clinical Oncology.

The best overall response to date was 29% partial response and 31% stable disease (60% clinical benefit rate) with a median of six cycles, said Dr. Soliman of the University of Texas MD Anderson Cancer Center, Houston.

So far, 58 patients have been enrolled in the study, and 194 cycles have been completed. Eight patients have received more than 14 cycles, and of those, 6 have achieved a partial response and 2 have stable disease.

Eight remain on active treatment.

“Of note, at the time of first assessment at 8 weeks, the objective response rate was only 14%, so over half of the responses were seen after at least 4 cycles of therapy were administered,” she said.

Endometrial cancer is the most common gynecologic malignancy, with an estimated 52,000 cases to be diagnosed this year. Most cases are diagnosed early, and the overall prognosis is good; the 5-year survival rate is nearly 90%.

“Unfortunately, for those women who recur, treatment options are limited,” Dr. Soliman said, noting that the best response rate seen in studies of various single and combination chemotherapy agents has been about 25% – occurring with paclitaxel and with bevacizumab-temsirolimus.

The novel combination therapy used in the current study was developed based on prior studies, including one conducted by Dr. Soliman and her colleagues, showing promising results with combination everolimus and letrozole for recurrent EEC. The investigators found that in one study of 35 patients on the everolimus and letrozole regimen, the overall response rate was 23%, the clinical benefit rate was 38%, and progression-free survival was 1.9 months, but they noticed that in a subgroup of patients who had received metformin during the course of the study, the corresponding rates were 56%, 78%, and 14 months. Preclinical data suggested that the benefit of adding metformin to the combination was particularly pronounced in patients with KRAS mutation. The current study was designed to evaluate this approach.

Study subjects had advanced/recurrent EEC and up to two prior chemotherapy regimens for recurrence. Molecular testing was performed to determine KRAS mutation status.

A pretreatment biopsy was performed for histological confirmation and molecular analysis, followed by a 1 week metformin lead in and then treatment with 10 mg oral everolimus daily, 2.5 mg or oral letrozole daily, and 500 mg of oral metformin twice daily. A single dose reduction of everolimus was permitted, and patients were treated until their disease progressed or until they experienced toxicity. Response was evaluated by imaging at 8 weeks or after 2 cycles of therapy, and confirmation of response was performed at 16 weeks, or after 4 cycles of therapy.

In this preliminary evaluation, no significant difference was seen in the clinical benefit rate based on KRAS mutation status (67% in 15 patients with KRAS mutation, 77% in 26 patients without the mutation), but further correlation between molecular findings and response are currently being evaluated.

The most common side effects were diarrhea, anemia, fatigue, nausea, mucositis, hypertriglyceridemia, and elevated aspartate aminotransferase, Dr. Soliman said, noting that 43% of patients experienced a grade 3/4 toxicity, 4 required a dose reduction, and 2 withdrew from the study.

Additionally, one patient with a partial response after 1 cycle was removed from treatment due to increased liver enzymes.

A comparison with findings from the prior everolimus and letrozole study showed that metformin did not add significant toxicity to the regimen, she noted.

“The addition of metformin to the everolimus and letrozole backbone, increased the clinical benefit rate from 40% to 60%. Overall the toxicity of all three drugs was manageable and few patients came off study due to toxicity ... Based on these findings and other studies, the use of targeted therapy in women with recurrent endometrial endometrioid cancer appears to benefit patients over standard cytotoxic chemotherapy,” Dr. Soliman concluded, adding that further development of this combination for use in patients with EEC is warranted.

She noted that an ongoing randomized clinical trial – GOG 3007 – is comparing everolimus and letrozole with tamoxifen alternating with megestrol acetate.

“This trial has recently completed accrual and results are pending. This will allow us to better identify how this treatment strategy compares to hormonal therapy alone in women with recurrent endometrial cancer. In addition, at our institution we are investigating other agents to be added to the everolimus and letrozole backbone to enhance response to patients with endometrioid endometrial cancer,” she said.

Dr. Soliman reported receiving research funding (to her institution) from Novartis.

[email protected]

CHICAGO – The novel combination of everolimus, letrozole, and metformin was associated with improved clinical benefit and objective response rates, compared with everolimus and letrozole without metformin in patients with advanced or recurrent, previously treated endometrioid endometrial cancer (EEC) in an ongoing open-label, single-arm, prospective phase II study.

Frontline Medical News

In 49 patients with an evaluable response to the combination therapy, 29 (60%) derived clinical benefit – defined as complete response, partial response, or stable disease confirmed at 8 weeks by RECIST 1.1, Dr. Pamela T. Soliman reported at the annual meeting of the American Society of Clinical Oncology.

The best overall response to date was 29% partial response and 31% stable disease (60% clinical benefit rate) with a median of six cycles, said Dr. Soliman of the University of Texas MD Anderson Cancer Center, Houston.

So far, 58 patients have been enrolled in the study, and 194 cycles have been completed. Eight patients have received more than 14 cycles, and of those, 6 have achieved a partial response and 2 have stable disease.

Eight remain on active treatment.

“Of note, at the time of first assessment at 8 weeks, the objective response rate was only 14%, so over half of the responses were seen after at least 4 cycles of therapy were administered,” she said.

Endometrial cancer is the most common gynecologic malignancy, with an estimated 52,000 cases to be diagnosed this year. Most cases are diagnosed early, and the overall prognosis is good; the 5-year survival rate is nearly 90%.

“Unfortunately, for those women who recur, treatment options are limited,” Dr. Soliman said, noting that the best response rate seen in studies of various single and combination chemotherapy agents has been about 25% – occurring with paclitaxel and with bevacizumab-temsirolimus.

The novel combination therapy used in the current study was developed based on prior studies, including one conducted by Dr. Soliman and her colleagues, showing promising results with combination everolimus and letrozole for recurrent EEC. The investigators found that in one study of 35 patients on the everolimus and letrozole regimen, the overall response rate was 23%, the clinical benefit rate was 38%, and progression-free survival was 1.9 months, but they noticed that in a subgroup of patients who had received metformin during the course of the study, the corresponding rates were 56%, 78%, and 14 months. Preclinical data suggested that the benefit of adding metformin to the combination was particularly pronounced in patients with KRAS mutation. The current study was designed to evaluate this approach.

Study subjects had advanced/recurrent EEC and up to two prior chemotherapy regimens for recurrence. Molecular testing was performed to determine KRAS mutation status.

A pretreatment biopsy was performed for histological confirmation and molecular analysis, followed by a 1 week metformin lead in and then treatment with 10 mg oral everolimus daily, 2.5 mg or oral letrozole daily, and 500 mg of oral metformin twice daily. A single dose reduction of everolimus was permitted, and patients were treated until their disease progressed or until they experienced toxicity. Response was evaluated by imaging at 8 weeks or after 2 cycles of therapy, and confirmation of response was performed at 16 weeks, or after 4 cycles of therapy.

In this preliminary evaluation, no significant difference was seen in the clinical benefit rate based on KRAS mutation status (67% in 15 patients with KRAS mutation, 77% in 26 patients without the mutation), but further correlation between molecular findings and response are currently being evaluated.

The most common side effects were diarrhea, anemia, fatigue, nausea, mucositis, hypertriglyceridemia, and elevated aspartate aminotransferase, Dr. Soliman said, noting that 43% of patients experienced a grade 3/4 toxicity, 4 required a dose reduction, and 2 withdrew from the study.

Additionally, one patient with a partial response after 1 cycle was removed from treatment due to increased liver enzymes.

A comparison with findings from the prior everolimus and letrozole study showed that metformin did not add significant toxicity to the regimen, she noted.

“The addition of metformin to the everolimus and letrozole backbone, increased the clinical benefit rate from 40% to 60%. Overall the toxicity of all three drugs was manageable and few patients came off study due to toxicity ... Based on these findings and other studies, the use of targeted therapy in women with recurrent endometrial endometrioid cancer appears to benefit patients over standard cytotoxic chemotherapy,” Dr. Soliman concluded, adding that further development of this combination for use in patients with EEC is warranted.

She noted that an ongoing randomized clinical trial – GOG 3007 – is comparing everolimus and letrozole with tamoxifen alternating with megestrol acetate.

“This trial has recently completed accrual and results are pending. This will allow us to better identify how this treatment strategy compares to hormonal therapy alone in women with recurrent endometrial cancer. In addition, at our institution we are investigating other agents to be added to the everolimus and letrozole backbone to enhance response to patients with endometrioid endometrial cancer,” she said.

Dr. Soliman reported receiving research funding (to her institution) from Novartis.

[email protected]

CHICAGO – The novel combination of everolimus, letrozole, and metformin was associated with improved clinical benefit and objective response rates, compared with everolimus and letrozole without metformin in patients with advanced or recurrent, previously treated endometrioid endometrial cancer (EEC) in an ongoing open-label, single-arm, prospective phase II study.

Frontline Medical News

In 49 patients with an evaluable response to the combination therapy, 29 (60%) derived clinical benefit – defined as complete response, partial response, or stable disease confirmed at 8 weeks by RECIST 1.1, Dr. Pamela T. Soliman reported at the annual meeting of the American Society of Clinical Oncology.

The best overall response to date was 29% partial response and 31% stable disease (60% clinical benefit rate) with a median of six cycles, said Dr. Soliman of the University of Texas MD Anderson Cancer Center, Houston.

So far, 58 patients have been enrolled in the study, and 194 cycles have been completed. Eight patients have received more than 14 cycles, and of those, 6 have achieved a partial response and 2 have stable disease.

Eight remain on active treatment.

“Of note, at the time of first assessment at 8 weeks, the objective response rate was only 14%, so over half of the responses were seen after at least 4 cycles of therapy were administered,” she said.

Endometrial cancer is the most common gynecologic malignancy, with an estimated 52,000 cases to be diagnosed this year. Most cases are diagnosed early, and the overall prognosis is good; the 5-year survival rate is nearly 90%.

“Unfortunately, for those women who recur, treatment options are limited,” Dr. Soliman said, noting that the best response rate seen in studies of various single and combination chemotherapy agents has been about 25% – occurring with paclitaxel and with bevacizumab-temsirolimus.

The novel combination therapy used in the current study was developed based on prior studies, including one conducted by Dr. Soliman and her colleagues, showing promising results with combination everolimus and letrozole for recurrent EEC. The investigators found that in one study of 35 patients on the everolimus and letrozole regimen, the overall response rate was 23%, the clinical benefit rate was 38%, and progression-free survival was 1.9 months, but they noticed that in a subgroup of patients who had received metformin during the course of the study, the corresponding rates were 56%, 78%, and 14 months. Preclinical data suggested that the benefit of adding metformin to the combination was particularly pronounced in patients with KRAS mutation. The current study was designed to evaluate this approach.

Study subjects had advanced/recurrent EEC and up to two prior chemotherapy regimens for recurrence. Molecular testing was performed to determine KRAS mutation status.

A pretreatment biopsy was performed for histological confirmation and molecular analysis, followed by a 1 week metformin lead in and then treatment with 10 mg oral everolimus daily, 2.5 mg or oral letrozole daily, and 500 mg of oral metformin twice daily. A single dose reduction of everolimus was permitted, and patients were treated until their disease progressed or until they experienced toxicity. Response was evaluated by imaging at 8 weeks or after 2 cycles of therapy, and confirmation of response was performed at 16 weeks, or after 4 cycles of therapy.

In this preliminary evaluation, no significant difference was seen in the clinical benefit rate based on KRAS mutation status (67% in 15 patients with KRAS mutation, 77% in 26 patients without the mutation), but further correlation between molecular findings and response are currently being evaluated.

The most common side effects were diarrhea, anemia, fatigue, nausea, mucositis, hypertriglyceridemia, and elevated aspartate aminotransferase, Dr. Soliman said, noting that 43% of patients experienced a grade 3/4 toxicity, 4 required a dose reduction, and 2 withdrew from the study.

Additionally, one patient with a partial response after 1 cycle was removed from treatment due to increased liver enzymes.

A comparison with findings from the prior everolimus and letrozole study showed that metformin did not add significant toxicity to the regimen, she noted.

“The addition of metformin to the everolimus and letrozole backbone, increased the clinical benefit rate from 40% to 60%. Overall the toxicity of all three drugs was manageable and few patients came off study due to toxicity ... Based on these findings and other studies, the use of targeted therapy in women with recurrent endometrial endometrioid cancer appears to benefit patients over standard cytotoxic chemotherapy,” Dr. Soliman concluded, adding that further development of this combination for use in patients with EEC is warranted.

She noted that an ongoing randomized clinical trial – GOG 3007 – is comparing everolimus and letrozole with tamoxifen alternating with megestrol acetate.

“This trial has recently completed accrual and results are pending. This will allow us to better identify how this treatment strategy compares to hormonal therapy alone in women with recurrent endometrial cancer. In addition, at our institution we are investigating other agents to be added to the everolimus and letrozole backbone to enhance response to patients with endometrioid endometrial cancer,” she said.

Dr. Soliman reported receiving research funding (to her institution) from Novartis.

[email protected]

Clinical question: What are the effects of implementing standardized clinical pathways on length of stay, cost, readmissions, and patient quality of life?

Background: As payment models shift from volume- to value-based models, standardized clinical pathways are one option to simultaneously provide high-value care, improve quality, and control costs. Studies of individual clinical pathways suggest that they may be helpful in decreasing utilization, but the measured impact has varied significantly. It is unknown how much of the measured effect is due to the pathway and how much is due to the clinical factors of the disease or patient population studied. No prior studies have evaluated a suite of clinical pathways in pediatric populations.

Study design: Retrospective cohort study.

Setting: Single, 250-bed, tertiary care, freestanding children’s hospital.

Synopsis: Over four years, 15 clinical pathways were created for common pediatric medical, surgical, and psychiatric complaints (urinary tract infection, diabetes, both diabetic ketoacidosis [DKA] and non-DKA, fractures, spinal surgery, croup, neonatal jaundice, neonatal fever, depressive disorders, pyloric stenosis, pneumonia, tonsillectomy and adenoidectomy, disruptive behavior, and cellulitis/abscess).

The pathways were implemented when they were complete, with guidelines coming online throughout the study period. Implementation included an order set in the electronic medical record that included relevant literature references and decision support, online training, and integration into the clinical workflow for providers and nurses. Use of the pathways was monitored, and they were reviewed on at least a quarterly basis and revised, if necessary.

The authors examined pathway use for eligible patients, hospital costs, length of stay, 30-day readmissions, and parent-reported quality of life, both before and after pathway implementation. Patients meeting criteria for complex chronic conditions were excluded from the study.

Before implementation, 3,808 admissions fulfilled pathway criteria, and 2,902 fulfilled criteria after implementation. The pathway for depressive disorders was the most used pathway, with 411 admissions and 95% of eligible patients on the pathway. Both pyloric stenosis and neonatal jaundice had 100% pathway use.

The lowest rate of pathway use was for urinary tract infection (20%). Pathway implementation slowed the rate of rise of hospital costs. Prior to study implementation, the costs were increasing by $126 per month. Following implementation, costs decreased by $29 per month (95% CI, $100 decrease to $34 increase; P=.001). Post-implementation, the length of stay for pathway-eligible patients began a statistically significant downward trend at a rate that yielded a decrease in length of stay of 8.6 hours over a year (P=0.02). There were no differences in 30-day readmissions or parent-reported quality of life.

Bottom line: Systematic development and implementation of clinical pathways for a variety of conditions can contain costs and decrease length of stay while maintaining clinical outcomes and not increasing readmissions.

Citation: Lion KC, Wright DR, Spencer S, Zhou C, Del Beccaro M, Mangione-Smith R. Standardized clinical pathways for hospitalized children and outcomes. Pediatrics. 2016;137(4). pii:e20151202. doi:10.1542/peds.2015-1202.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

Clinical question: What are the effects of implementing standardized clinical pathways on length of stay, cost, readmissions, and patient quality of life?

Background: As payment models shift from volume- to value-based models, standardized clinical pathways are one option to simultaneously provide high-value care, improve quality, and control costs. Studies of individual clinical pathways suggest that they may be helpful in decreasing utilization, but the measured impact has varied significantly. It is unknown how much of the measured effect is due to the pathway and how much is due to the clinical factors of the disease or patient population studied. No prior studies have evaluated a suite of clinical pathways in pediatric populations.

Study design: Retrospective cohort study.

Setting: Single, 250-bed, tertiary care, freestanding children’s hospital.

Synopsis: Over four years, 15 clinical pathways were created for common pediatric medical, surgical, and psychiatric complaints (urinary tract infection, diabetes, both diabetic ketoacidosis [DKA] and non-DKA, fractures, spinal surgery, croup, neonatal jaundice, neonatal fever, depressive disorders, pyloric stenosis, pneumonia, tonsillectomy and adenoidectomy, disruptive behavior, and cellulitis/abscess).

The pathways were implemented when they were complete, with guidelines coming online throughout the study period. Implementation included an order set in the electronic medical record that included relevant literature references and decision support, online training, and integration into the clinical workflow for providers and nurses. Use of the pathways was monitored, and they were reviewed on at least a quarterly basis and revised, if necessary.

The authors examined pathway use for eligible patients, hospital costs, length of stay, 30-day readmissions, and parent-reported quality of life, both before and after pathway implementation. Patients meeting criteria for complex chronic conditions were excluded from the study.

Before implementation, 3,808 admissions fulfilled pathway criteria, and 2,902 fulfilled criteria after implementation. The pathway for depressive disorders was the most used pathway, with 411 admissions and 95% of eligible patients on the pathway. Both pyloric stenosis and neonatal jaundice had 100% pathway use.

The lowest rate of pathway use was for urinary tract infection (20%). Pathway implementation slowed the rate of rise of hospital costs. Prior to study implementation, the costs were increasing by $126 per month. Following implementation, costs decreased by $29 per month (95% CI, $100 decrease to $34 increase; P=.001). Post-implementation, the length of stay for pathway-eligible patients began a statistically significant downward trend at a rate that yielded a decrease in length of stay of 8.6 hours over a year (P=0.02). There were no differences in 30-day readmissions or parent-reported quality of life.

Bottom line: Systematic development and implementation of clinical pathways for a variety of conditions can contain costs and decrease length of stay while maintaining clinical outcomes and not increasing readmissions.

Citation: Lion KC, Wright DR, Spencer S, Zhou C, Del Beccaro M, Mangione-Smith R. Standardized clinical pathways for hospitalized children and outcomes. Pediatrics. 2016;137(4). pii:e20151202. doi:10.1542/peds.2015-1202.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

Clinical question: What are the effects of implementing standardized clinical pathways on length of stay, cost, readmissions, and patient quality of life?

Background: As payment models shift from volume- to value-based models, standardized clinical pathways are one option to simultaneously provide high-value care, improve quality, and control costs. Studies of individual clinical pathways suggest that they may be helpful in decreasing utilization, but the measured impact has varied significantly. It is unknown how much of the measured effect is due to the pathway and how much is due to the clinical factors of the disease or patient population studied. No prior studies have evaluated a suite of clinical pathways in pediatric populations.

Study design: Retrospective cohort study.

Setting: Single, 250-bed, tertiary care, freestanding children’s hospital.

Synopsis: Over four years, 15 clinical pathways were created for common pediatric medical, surgical, and psychiatric complaints (urinary tract infection, diabetes, both diabetic ketoacidosis [DKA] and non-DKA, fractures, spinal surgery, croup, neonatal jaundice, neonatal fever, depressive disorders, pyloric stenosis, pneumonia, tonsillectomy and adenoidectomy, disruptive behavior, and cellulitis/abscess).

The pathways were implemented when they were complete, with guidelines coming online throughout the study period. Implementation included an order set in the electronic medical record that included relevant literature references and decision support, online training, and integration into the clinical workflow for providers and nurses. Use of the pathways was monitored, and they were reviewed on at least a quarterly basis and revised, if necessary.

The authors examined pathway use for eligible patients, hospital costs, length of stay, 30-day readmissions, and parent-reported quality of life, both before and after pathway implementation. Patients meeting criteria for complex chronic conditions were excluded from the study.

Before implementation, 3,808 admissions fulfilled pathway criteria, and 2,902 fulfilled criteria after implementation. The pathway for depressive disorders was the most used pathway, with 411 admissions and 95% of eligible patients on the pathway. Both pyloric stenosis and neonatal jaundice had 100% pathway use.

The lowest rate of pathway use was for urinary tract infection (20%). Pathway implementation slowed the rate of rise of hospital costs. Prior to study implementation, the costs were increasing by $126 per month. Following implementation, costs decreased by $29 per month (95% CI, $100 decrease to $34 increase; P=.001). Post-implementation, the length of stay for pathway-eligible patients began a statistically significant downward trend at a rate that yielded a decrease in length of stay of 8.6 hours over a year (P=0.02). There were no differences in 30-day readmissions or parent-reported quality of life.

Bottom line: Systematic development and implementation of clinical pathways for a variety of conditions can contain costs and decrease length of stay while maintaining clinical outcomes and not increasing readmissions.

Citation: Lion KC, Wright DR, Spencer S, Zhou C, Del Beccaro M, Mangione-Smith R. Standardized clinical pathways for hospitalized children and outcomes. Pediatrics. 2016;137(4). pii:e20151202. doi:10.1542/peds.2015-1202.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. Dupont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

Attendees at ASCO 2016

© ASCO/Brian Powers

CHICAGO—Treatment dose and schedule, as well as a patient’s tumor burden, influence the outcome of therapy with chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASCO Annual Meeting.

One presentation suggested the dose and schedule of CTL019 can impact both complete response (CR) rates and the incidence of cytokine release syndrome (CRS).

Another presentation indicated that disease burden may determine the risk of toxicity and correlate with the efficacy of JCAR015.

CTL019

Noelle Frey, MD, of the University of Pennsylvania in Philadelphia, presented results observed with CTL019 in 30 adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated on 2 trials (NCT02030847 and NCT01029366) as abstract 7002.*

Dr Frey noted that CAR T-cell therapies, including CTL019, have led to “unprecedented remission rates of between 70% and 90%.” However, immune activation that leads to high response rates also confers significant treatment-related toxicity—namely, CRS.

She reported that, in the 2 trials of adult ALL patients, a high dose of CTL019 led to a 100% response rate and a 100% CRS rate. Splitting the dose over 3 days led to an 86% response rate and a 66% CRS rate. A single low dose reduced efficacy to 33% and CRS to 66%.

Three of 6 patients who received a single high dose developed CRS and died within weeks. All of these patients had infections or sepsis that likely led to their deaths, Dr Frey said. She suggested clinicians aggressively monitor infections and treat with antimicrobials prior to CAR T-cell therapy.

“The infusion dose and schedule of CTL019 correlate with toxicity and response,” she observed. “A fractionated dosing scheme allows for real-time intra-patient dose modification in response to toxicity and the maintenance of high response rates. Concurrent sepsis and CRS confers a poor outcome.”

Dr Frey said future studies will determine the optimal approach to minimize toxicity while maintaining high efficacy. A fractionated dosing scheme is only one way to mitigate CRS. Other attractive approaches include inverse dosing based on disease burden and varying the timing of anti-cytokine-directed therapy.

JCAR015

Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, reported data from a phase 1 clinical trial (NCT01044069) of JCAR015 in 51 adults with relapsed/refractory ALL as abstract 7003.*

Treatment with JCAR015 led to high CR rates and minimal residual disease (MRD)-negativity, regardless of the amount of disease at baseline. However, outcomes were superior among patients with minimal disease at baseline.

For patients with morphologic disease, 77% achieved a CR by 20 days after treatment, and 90% were MRD-negative.

For those with minimal disease, 90% achieved a CR by 25 days after treatment, and 78% were MRD-negative. These patients experienced significantly less CRS and neurotoxicity than patients with morphologic disease.

“High CR and MRD-negativity rates were observed regardless of pre-T-cell burden,” Dr Park noted. “We observed durable responses and survivals in a subset of patients with no subsequent allotransplant in both morphological and minimal disease cohorts.”

*Data in the abstracts differ from the presentations.

Attendees at ASCO 2016

© ASCO/Brian Powers

CHICAGO—Treatment dose and schedule, as well as a patient’s tumor burden, influence the outcome of therapy with chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASCO Annual Meeting.

One presentation suggested the dose and schedule of CTL019 can impact both complete response (CR) rates and the incidence of cytokine release syndrome (CRS).

Another presentation indicated that disease burden may determine the risk of toxicity and correlate with the efficacy of JCAR015.

CTL019

Noelle Frey, MD, of the University of Pennsylvania in Philadelphia, presented results observed with CTL019 in 30 adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated on 2 trials (NCT02030847 and NCT01029366) as abstract 7002.*

Dr Frey noted that CAR T-cell therapies, including CTL019, have led to “unprecedented remission rates of between 70% and 90%.” However, immune activation that leads to high response rates also confers significant treatment-related toxicity—namely, CRS.

She reported that, in the 2 trials of adult ALL patients, a high dose of CTL019 led to a 100% response rate and a 100% CRS rate. Splitting the dose over 3 days led to an 86% response rate and a 66% CRS rate. A single low dose reduced efficacy to 33% and CRS to 66%.

Three of 6 patients who received a single high dose developed CRS and died within weeks. All of these patients had infections or sepsis that likely led to their deaths, Dr Frey said. She suggested clinicians aggressively monitor infections and treat with antimicrobials prior to CAR T-cell therapy.

“The infusion dose and schedule of CTL019 correlate with toxicity and response,” she observed. “A fractionated dosing scheme allows for real-time intra-patient dose modification in response to toxicity and the maintenance of high response rates. Concurrent sepsis and CRS confers a poor outcome.”

Dr Frey said future studies will determine the optimal approach to minimize toxicity while maintaining high efficacy. A fractionated dosing scheme is only one way to mitigate CRS. Other attractive approaches include inverse dosing based on disease burden and varying the timing of anti-cytokine-directed therapy.

JCAR015

Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, reported data from a phase 1 clinical trial (NCT01044069) of JCAR015 in 51 adults with relapsed/refractory ALL as abstract 7003.*

Treatment with JCAR015 led to high CR rates and minimal residual disease (MRD)-negativity, regardless of the amount of disease at baseline. However, outcomes were superior among patients with minimal disease at baseline.

For patients with morphologic disease, 77% achieved a CR by 20 days after treatment, and 90% were MRD-negative.

For those with minimal disease, 90% achieved a CR by 25 days after treatment, and 78% were MRD-negative. These patients experienced significantly less CRS and neurotoxicity than patients with morphologic disease.

“High CR and MRD-negativity rates were observed regardless of pre-T-cell burden,” Dr Park noted. “We observed durable responses and survivals in a subset of patients with no subsequent allotransplant in both morphological and minimal disease cohorts.”

*Data in the abstracts differ from the presentations.

Attendees at ASCO 2016

© ASCO/Brian Powers

CHICAGO—Treatment dose and schedule, as well as a patient’s tumor burden, influence the outcome of therapy with chimeric antigen receptor (CAR) T cells, according to research presented at the 2016 ASCO Annual Meeting.

One presentation suggested the dose and schedule of CTL019 can impact both complete response (CR) rates and the incidence of cytokine release syndrome (CRS).

Another presentation indicated that disease burden may determine the risk of toxicity and correlate with the efficacy of JCAR015.

CTL019

Noelle Frey, MD, of the University of Pennsylvania in Philadelphia, presented results observed with CTL019 in 30 adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated on 2 trials (NCT02030847 and NCT01029366) as abstract 7002.*

Dr Frey noted that CAR T-cell therapies, including CTL019, have led to “unprecedented remission rates of between 70% and 90%.” However, immune activation that leads to high response rates also confers significant treatment-related toxicity—namely, CRS.

She reported that, in the 2 trials of adult ALL patients, a high dose of CTL019 led to a 100% response rate and a 100% CRS rate. Splitting the dose over 3 days led to an 86% response rate and a 66% CRS rate. A single low dose reduced efficacy to 33% and CRS to 66%.

Three of 6 patients who received a single high dose developed CRS and died within weeks. All of these patients had infections or sepsis that likely led to their deaths, Dr Frey said. She suggested clinicians aggressively monitor infections and treat with antimicrobials prior to CAR T-cell therapy.

“The infusion dose and schedule of CTL019 correlate with toxicity and response,” she observed. “A fractionated dosing scheme allows for real-time intra-patient dose modification in response to toxicity and the maintenance of high response rates. Concurrent sepsis and CRS confers a poor outcome.”

Dr Frey said future studies will determine the optimal approach to minimize toxicity while maintaining high efficacy. A fractionated dosing scheme is only one way to mitigate CRS. Other attractive approaches include inverse dosing based on disease burden and varying the timing of anti-cytokine-directed therapy.

JCAR015

Jae Park, MD, of Memorial Sloan Kettering Cancer Center in New York, reported data from a phase 1 clinical trial (NCT01044069) of JCAR015 in 51 adults with relapsed/refractory ALL as abstract 7003.*

Treatment with JCAR015 led to high CR rates and minimal residual disease (MRD)-negativity, regardless of the amount of disease at baseline. However, outcomes were superior among patients with minimal disease at baseline.

For patients with morphologic disease, 77% achieved a CR by 20 days after treatment, and 90% were MRD-negative.

For those with minimal disease, 90% achieved a CR by 25 days after treatment, and 78% were MRD-negative. These patients experienced significantly less CRS and neurotoxicity than patients with morphologic disease.

“High CR and MRD-negativity rates were observed regardless of pre-T-cell burden,” Dr Park noted. “We observed durable responses and survivals in a subset of patients with no subsequent allotransplant in both morphological and minimal disease cohorts.”

*Data in the abstracts differ from the presentations.

McCormick Place, site of

the ASCO Annual Meeting

© ASCO/Todd Buchanan

CHICAGO—Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant (ASCT) should be considered the standard of care in

newly diagnosed multiple myeloma (MM) patients, according to a meta-analysis presented at the 2016 ASCO Annual Meeting.

Lenalidomide maintenance increased overall survival (OS), with a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival.

Several studies have demonstrated that lenalidomide maintenance post-ASCT reduces the risk of disease progression or death in patients with MM by about 50%.

However, these studies were not powered for OS, said Philip McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, New York.

With this in mind, Dr McCarthy and his colleagues conducted a meta-analysis to assess the effect of post-ASCT lenalidomide maintenance on OS using a pooled analysis of primary source patient data. A search revealed 17 randomized, controlled trials using lenalidomide post-ASCT.

Three trials met pre-specified inclusion criteria and had sufficient OS events to test a treatment effect. The studies intended for lenalidomide maintenance to be given until progression.

In these trials, 1209 MM patients, with a median age of 58, were randomized from 2005 to 2009 to receive lenalidomide (605 patients) at 10 mg/day on days 1-21/28 or days 1-28/28. The remaining 604 patients served as controls. Baseline characteristics were generally balanced between the 2 groups.

With a median follow-up of 6.6 years, 491 patients (41%) had died.

After induction and single (82%) or tandem (18%) ASCT, 55% of patients achieved a complete response (CR) or very good partial response.

The median OS has not been reached in the lenalidomide arm but was 86 months for the control arm.

“There is a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival,” Dr McCarthy said.

The OS benefit favoring lenalidomide was generally consistent across the majority of subgroup analyses, including age, sex, ISS stage, response after ASCT, and prior induction therapy.

All studies contributed to the positive results of the meta-analysis. Heterogeneity tests showed significant differences across trials, mainly because of a difference in the magnitude of treatment effect, Dr McCarthy said.

The mean treatment duration of maintenance was 25 to 30 months in the lenalidomide group and 13 to 20 months in controls. About one-third to more than half of the patients received therapy for 3 or more years, Dr McCarthy said.

Lenalidomide led to an increased risk in the cumulative incidence of hematologic and solid tumor second primary malignancies. However, Dr McCarthy said the OS benefit of lenalidomide maintenance outweighs the risk of developing second primary malignancy.

“This large meta-analysis demonstrates that lenalidomide maintenance significantly prolonged OS post-ASCT, including in patients who achieved CR, demonstrating benefit in patients in all response categories,” Dr McCarthy said.

“Lenalidomide maintenance after ASCT can be considered a standard of care for newly diagnosed multiple myeloma patients. However, we have more to learn. Understanding the role of minimal residual disease detection and immune reconstitution after transplant should allow us to further improve OS. Critically, developing early endpoints as surrogates for long-term outcome and OS is important for the future. Otherwise, trials may continue for 10 years or longer.”

Dr McCarthy presented these findings as abstract 8001.

McCormick Place, site of

the ASCO Annual Meeting

© ASCO/Todd Buchanan

CHICAGO—Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant (ASCT) should be considered the standard of care in

newly diagnosed multiple myeloma (MM) patients, according to a meta-analysis presented at the 2016 ASCO Annual Meeting.

Lenalidomide maintenance increased overall survival (OS), with a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival.

Several studies have demonstrated that lenalidomide maintenance post-ASCT reduces the risk of disease progression or death in patients with MM by about 50%.

However, these studies were not powered for OS, said Philip McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, New York.

With this in mind, Dr McCarthy and his colleagues conducted a meta-analysis to assess the effect of post-ASCT lenalidomide maintenance on OS using a pooled analysis of primary source patient data. A search revealed 17 randomized, controlled trials using lenalidomide post-ASCT.

Three trials met pre-specified inclusion criteria and had sufficient OS events to test a treatment effect. The studies intended for lenalidomide maintenance to be given until progression.

In these trials, 1209 MM patients, with a median age of 58, were randomized from 2005 to 2009 to receive lenalidomide (605 patients) at 10 mg/day on days 1-21/28 or days 1-28/28. The remaining 604 patients served as controls. Baseline characteristics were generally balanced between the 2 groups.

With a median follow-up of 6.6 years, 491 patients (41%) had died.

After induction and single (82%) or tandem (18%) ASCT, 55% of patients achieved a complete response (CR) or very good partial response.

The median OS has not been reached in the lenalidomide arm but was 86 months for the control arm.

“There is a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival,” Dr McCarthy said.

The OS benefit favoring lenalidomide was generally consistent across the majority of subgroup analyses, including age, sex, ISS stage, response after ASCT, and prior induction therapy.

All studies contributed to the positive results of the meta-analysis. Heterogeneity tests showed significant differences across trials, mainly because of a difference in the magnitude of treatment effect, Dr McCarthy said.

The mean treatment duration of maintenance was 25 to 30 months in the lenalidomide group and 13 to 20 months in controls. About one-third to more than half of the patients received therapy for 3 or more years, Dr McCarthy said.

Lenalidomide led to an increased risk in the cumulative incidence of hematologic and solid tumor second primary malignancies. However, Dr McCarthy said the OS benefit of lenalidomide maintenance outweighs the risk of developing second primary malignancy.

“This large meta-analysis demonstrates that lenalidomide maintenance significantly prolonged OS post-ASCT, including in patients who achieved CR, demonstrating benefit in patients in all response categories,” Dr McCarthy said.

“Lenalidomide maintenance after ASCT can be considered a standard of care for newly diagnosed multiple myeloma patients. However, we have more to learn. Understanding the role of minimal residual disease detection and immune reconstitution after transplant should allow us to further improve OS. Critically, developing early endpoints as surrogates for long-term outcome and OS is important for the future. Otherwise, trials may continue for 10 years or longer.”

Dr McCarthy presented these findings as abstract 8001.

McCormick Place, site of

the ASCO Annual Meeting

© ASCO/Todd Buchanan

CHICAGO—Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant (ASCT) should be considered the standard of care in

newly diagnosed multiple myeloma (MM) patients, according to a meta-analysis presented at the 2016 ASCO Annual Meeting.

Lenalidomide maintenance increased overall survival (OS), with a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival.

Several studies have demonstrated that lenalidomide maintenance post-ASCT reduces the risk of disease progression or death in patients with MM by about 50%.

However, these studies were not powered for OS, said Philip McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, New York.

With this in mind, Dr McCarthy and his colleagues conducted a meta-analysis to assess the effect of post-ASCT lenalidomide maintenance on OS using a pooled analysis of primary source patient data. A search revealed 17 randomized, controlled trials using lenalidomide post-ASCT.

Three trials met pre-specified inclusion criteria and had sufficient OS events to test a treatment effect. The studies intended for lenalidomide maintenance to be given until progression.

In these trials, 1209 MM patients, with a median age of 58, were randomized from 2005 to 2009 to receive lenalidomide (605 patients) at 10 mg/day on days 1-21/28 or days 1-28/28. The remaining 604 patients served as controls. Baseline characteristics were generally balanced between the 2 groups.

With a median follow-up of 6.6 years, 491 patients (41%) had died.

After induction and single (82%) or tandem (18%) ASCT, 55% of patients achieved a complete response (CR) or very good partial response.

The median OS has not been reached in the lenalidomide arm but was 86 months for the control arm.

“There is a 26% reduction in the risk of death, representing an estimated 2.5-year increase in median survival,” Dr McCarthy said.

The OS benefit favoring lenalidomide was generally consistent across the majority of subgroup analyses, including age, sex, ISS stage, response after ASCT, and prior induction therapy.

All studies contributed to the positive results of the meta-analysis. Heterogeneity tests showed significant differences across trials, mainly because of a difference in the magnitude of treatment effect, Dr McCarthy said.

The mean treatment duration of maintenance was 25 to 30 months in the lenalidomide group and 13 to 20 months in controls. About one-third to more than half of the patients received therapy for 3 or more years, Dr McCarthy said.

Lenalidomide led to an increased risk in the cumulative incidence of hematologic and solid tumor second primary malignancies. However, Dr McCarthy said the OS benefit of lenalidomide maintenance outweighs the risk of developing second primary malignancy.

“This large meta-analysis demonstrates that lenalidomide maintenance significantly prolonged OS post-ASCT, including in patients who achieved CR, demonstrating benefit in patients in all response categories,” Dr McCarthy said.

“Lenalidomide maintenance after ASCT can be considered a standard of care for newly diagnosed multiple myeloma patients. However, we have more to learn. Understanding the role of minimal residual disease detection and immune reconstitution after transplant should allow us to further improve OS. Critically, developing early endpoints as surrogates for long-term outcome and OS is important for the future. Otherwise, trials may continue for 10 years or longer.”

Dr McCarthy presented these findings as abstract 8001.

HIV budding from a

cultured lymphocyte

Image courtesy of CDC

With the advent of effective anti-retroviral therapy, patients with HIV-related lymphoma receive standard therapeutic regimens and achieve outcomes comparable to those of non-HIV-infected individuals.

Based on results of a multicenter phase 2 study, this now extends to treatment with autologous stem cell transplant (ASCT).

Researchers found that outcomes were not significantly different between HIV-infected patients who received ASCT and matched controls.

“These findings are remarkably important for a group of patients who, up until now, have been inconsistently treated,” said lead study author Joseph C. Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.

“Based on our data, autologous stem cell transplant should be considered the standard of care for patients with HIV-related lymphomas for the same indications and under the same circumstances that we would use it in patients without HIV infection.”

To arrive at this recommendation, investigators enrolled 43 HIV-infected patients with relapsed or persistent non-Hodgkin lymphoma (NHL) or classical Hodgkin lymphoma (HL) onto the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0803/AIDS Malignancy Consortium (AMC) 071 study.

They reported their findings in Blood.

Eligibility

Patients had to be 15 years or older, have documented evidence of HIV infection, and have a Karnofsky performance status of greater than 70%.

They had to have persistent or recurrent diffuse large B-cell lymphoma, immunoblastic lymphoma, plasmablastic lymphoma, Burkitt lymphoma, Burkitt-like NHL, or classic HL.

Patients could have had no more than 3 prior treatment regimens or 2 or fewer salvage regimens.

They had to have adequate organ function, fewer than 10% blasts in their marrow, no prior autologous or allogeneic transplant, and adequate hematopoietic progenitor cell mobilization of more than 1.5 x 10⁶ CD34+ cells/kg to be eligible.

Transplant regimen

Patients received the BEAM (carmustine, etoposide, cytarabine, and melphalan) transplant regimen on day 0. They did not receive antiretroviral therapy from the time of the start of BEAM until 7 days after completion of the preparative regimen.

Efavirenz was held for 2 weeks prior to BEAM initiation, and an alternative agent was substituted during this time period. Zidovudine was prohibited following transplant because of its myelosuppressive effects.

Patients received growth factor, transfusion, and antimicrobial supportive care according to institutional standards of the transplant center.

Patient characteristics

Of the original 43 patients enrolled, 3 patients experienced disease progression prior to the conditioning regimen and did not undergo transplant. Therefore, investigators did not include them in the study analysis.

Forty patients received ASCT at 16 different transplant centers. They were a median age of 46.9 (range, 22.5–62.2), and 35 were male.

All patients received peripheral blood stem cell grafts at a median dose of 3.9 x 10⁶ CD34+ cells/kg (range, 1.6–11.0). And all patients were able to mobilize hematopoietic progenitor cells in a median of 2 apheresis collections (range, 1–5).

Most patients (n=32; 80%) had a pre-transplant HIV viral load that was undetectable. The median viral load for those 8 patients with detectable disease was 80 copies/mL (range, 50–17,455).

Patients had a median pre-transplant CD4+ T-cell count of 249.0 CD4+/μL (range, 39–797).

Investigators followed the patients for a median of 24.8 months (range, 2.8–27.2).

Response

Seven patients died during the follow-up period, 5 within 1 year of transplant. Four of the deaths within 1 year of transplant were due to relapse or disease progression.

One-year transplant-related mortality (TRM) was 5.2%.

The 1-year overall survival (OS) probability was 87.3%, and, at 2 years, it was 82%. The 2-year progression-free survival (PFS) was 79.8%, and the cumulative incidence of relapse/progression at 2 years was 12.5%.

The probabilities for OS and PFS at 2 years were comparable for both NHL and HL patients.

The median time to post-transplant neutrophil recovery was 11 days, and 97.5% of patients recovered their neutrophil counts by day 28.

The median time to platelet recovery was 18 days, and 92.5% of patients recovered their platelet counts by day 100.

At 100 days post-transplant, 28.9% of the evaluable patients (11/38) had recovered hematologic function. And at 1 year, 74.2% (23/31) had recovered hematologic function.

Adverse events

A little more than half (55%) the patients had at least 1 infectious event within a year of transplant, including 11 who had a severe infection.

Of the 57 infections that occurred post-transplant, 25 were due to bacteria, 22 to viruses, 6 to fungal organisms, 2 to protozoa, and 2 to other organisms. No patient developed Pneumocystis jiroveci pneumonia after transplant.

Nine patients experienced a total of 13 grade 3–5 adverse events. This included infection/sepsis (5 events), venous thromboembolism (2 events), and 1 event each for esophageal candidiasis, enteritis, hyperglycemia, hypernatremia, acute appendicitis, and acute coronary syndrome.

Sixteen patients had to be re-admitted to the hospital after the transplant, for a total of 34 readmissions. Infection (18) and fever (6) were the most common reasons for readmission.

Data comparison

The investigators compared the OS and PFS results to a control group identified through the Center for International Bone Marrow Transplant Research (CIBMTR).

One hundred fifty-one controls matched for age, performance status, primary disease, and disease status at transplant were identified for the 40 HIV-lymphoma cases.

The 1-year OS for the control group was 87.7%, and the 2-year PFS was 69.5%. This compared with the 87.3% and 79.8% for OS and PFS, respectively, for the HIV-lymphoma patients.

These results, the investigators wrote, were not significantly different from outcomes of CIBMTR controls, with a hazard ratio for overall mortality in the HIV-lymphoma patients of 0.67 (95% CI: 0.30–1.50, P=0.33) compared to controls.

And the hazard ratio for treatment failure in the HIV-lymphoma patients was 0.52 (95% CI: 0.2927–1.03, P=0.06) compared to controls.

The investigators concluded that HIV infection alone should not be considered a contraindication to ASCT for patients who otherwise meet transplant inclusion criteria. And ASCT should be considered the standard of care for patients with HIV-related lymphoma, provided that the HIV infection is treatment-responsive.

The team added that these patients should also be considered “appropriate potential participants” for future ASCT clinical trials.

HIV budding from a

cultured lymphocyte

Image courtesy of CDC

With the advent of effective anti-retroviral therapy, patients with HIV-related lymphoma receive standard therapeutic regimens and achieve outcomes comparable to those of non-HIV-infected individuals.

Based on results of a multicenter phase 2 study, this now extends to treatment with autologous stem cell transplant (ASCT).

Researchers found that outcomes were not significantly different between HIV-infected patients who received ASCT and matched controls.

“These findings are remarkably important for a group of patients who, up until now, have been inconsistently treated,” said lead study author Joseph C. Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.

“Based on our data, autologous stem cell transplant should be considered the standard of care for patients with HIV-related lymphomas for the same indications and under the same circumstances that we would use it in patients without HIV infection.”

To arrive at this recommendation, investigators enrolled 43 HIV-infected patients with relapsed or persistent non-Hodgkin lymphoma (NHL) or classical Hodgkin lymphoma (HL) onto the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0803/AIDS Malignancy Consortium (AMC) 071 study.

They reported their findings in Blood.

Eligibility

Patients had to be 15 years or older, have documented evidence of HIV infection, and have a Karnofsky performance status of greater than 70%.

They had to have persistent or recurrent diffuse large B-cell lymphoma, immunoblastic lymphoma, plasmablastic lymphoma, Burkitt lymphoma, Burkitt-like NHL, or classic HL.

Patients could have had no more than 3 prior treatment regimens or 2 or fewer salvage regimens.

They had to have adequate organ function, fewer than 10% blasts in their marrow, no prior autologous or allogeneic transplant, and adequate hematopoietic progenitor cell mobilization of more than 1.5 x 10⁶ CD34+ cells/kg to be eligible.

Transplant regimen

Patients received the BEAM (carmustine, etoposide, cytarabine, and melphalan) transplant regimen on day 0. They did not receive antiretroviral therapy from the time of the start of BEAM until 7 days after completion of the preparative regimen.

Efavirenz was held for 2 weeks prior to BEAM initiation, and an alternative agent was substituted during this time period. Zidovudine was prohibited following transplant because of its myelosuppressive effects.

Patients received growth factor, transfusion, and antimicrobial supportive care according to institutional standards of the transplant center.

Patient characteristics

Of the original 43 patients enrolled, 3 patients experienced disease progression prior to the conditioning regimen and did not undergo transplant. Therefore, investigators did not include them in the study analysis.

Forty patients received ASCT at 16 different transplant centers. They were a median age of 46.9 (range, 22.5–62.2), and 35 were male.

All patients received peripheral blood stem cell grafts at a median dose of 3.9 x 10⁶ CD34+ cells/kg (range, 1.6–11.0). And all patients were able to mobilize hematopoietic progenitor cells in a median of 2 apheresis collections (range, 1–5).

Most patients (n=32; 80%) had a pre-transplant HIV viral load that was undetectable. The median viral load for those 8 patients with detectable disease was 80 copies/mL (range, 50–17,455).

Patients had a median pre-transplant CD4+ T-cell count of 249.0 CD4+/μL (range, 39–797).

Investigators followed the patients for a median of 24.8 months (range, 2.8–27.2).

Response

Seven patients died during the follow-up period, 5 within 1 year of transplant. Four of the deaths within 1 year of transplant were due to relapse or disease progression.

One-year transplant-related mortality (TRM) was 5.2%.

The 1-year overall survival (OS) probability was 87.3%, and, at 2 years, it was 82%. The 2-year progression-free survival (PFS) was 79.8%, and the cumulative incidence of relapse/progression at 2 years was 12.5%.

The probabilities for OS and PFS at 2 years were comparable for both NHL and HL patients.

The median time to post-transplant neutrophil recovery was 11 days, and 97.5% of patients recovered their neutrophil counts by day 28.

The median time to platelet recovery was 18 days, and 92.5% of patients recovered their platelet counts by day 100.

At 100 days post-transplant, 28.9% of the evaluable patients (11/38) had recovered hematologic function. And at 1 year, 74.2% (23/31) had recovered hematologic function.

Adverse events

A little more than half (55%) the patients had at least 1 infectious event within a year of transplant, including 11 who had a severe infection.

Of the 57 infections that occurred post-transplant, 25 were due to bacteria, 22 to viruses, 6 to fungal organisms, 2 to protozoa, and 2 to other organisms. No patient developed Pneumocystis jiroveci pneumonia after transplant.

Nine patients experienced a total of 13 grade 3–5 adverse events. This included infection/sepsis (5 events), venous thromboembolism (2 events), and 1 event each for esophageal candidiasis, enteritis, hyperglycemia, hypernatremia, acute appendicitis, and acute coronary syndrome.

Sixteen patients had to be re-admitted to the hospital after the transplant, for a total of 34 readmissions. Infection (18) and fever (6) were the most common reasons for readmission.

Data comparison

The investigators compared the OS and PFS results to a control group identified through the Center for International Bone Marrow Transplant Research (CIBMTR).

One hundred fifty-one controls matched for age, performance status, primary disease, and disease status at transplant were identified for the 40 HIV-lymphoma cases.

The 1-year OS for the control group was 87.7%, and the 2-year PFS was 69.5%. This compared with the 87.3% and 79.8% for OS and PFS, respectively, for the HIV-lymphoma patients.

These results, the investigators wrote, were not significantly different from outcomes of CIBMTR controls, with a hazard ratio for overall mortality in the HIV-lymphoma patients of 0.67 (95% CI: 0.30–1.50, P=0.33) compared to controls.

And the hazard ratio for treatment failure in the HIV-lymphoma patients was 0.52 (95% CI: 0.2927–1.03, P=0.06) compared to controls.

The investigators concluded that HIV infection alone should not be considered a contraindication to ASCT for patients who otherwise meet transplant inclusion criteria. And ASCT should be considered the standard of care for patients with HIV-related lymphoma, provided that the HIV infection is treatment-responsive.

The team added that these patients should also be considered “appropriate potential participants” for future ASCT clinical trials.

HIV budding from a

cultured lymphocyte

Image courtesy of CDC

With the advent of effective anti-retroviral therapy, patients with HIV-related lymphoma receive standard therapeutic regimens and achieve outcomes comparable to those of non-HIV-infected individuals.

Based on results of a multicenter phase 2 study, this now extends to treatment with autologous stem cell transplant (ASCT).

Researchers found that outcomes were not significantly different between HIV-infected patients who received ASCT and matched controls.

“These findings are remarkably important for a group of patients who, up until now, have been inconsistently treated,” said lead study author Joseph C. Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.

“Based on our data, autologous stem cell transplant should be considered the standard of care for patients with HIV-related lymphomas for the same indications and under the same circumstances that we would use it in patients without HIV infection.”

To arrive at this recommendation, investigators enrolled 43 HIV-infected patients with relapsed or persistent non-Hodgkin lymphoma (NHL) or classical Hodgkin lymphoma (HL) onto the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0803/AIDS Malignancy Consortium (AMC) 071 study.

They reported their findings in Blood.

Eligibility

Patients had to be 15 years or older, have documented evidence of HIV infection, and have a Karnofsky performance status of greater than 70%.

They had to have persistent or recurrent diffuse large B-cell lymphoma, immunoblastic lymphoma, plasmablastic lymphoma, Burkitt lymphoma, Burkitt-like NHL, or classic HL.

Patients could have had no more than 3 prior treatment regimens or 2 or fewer salvage regimens.

They had to have adequate organ function, fewer than 10% blasts in their marrow, no prior autologous or allogeneic transplant, and adequate hematopoietic progenitor cell mobilization of more than 1.5 x 10⁶ CD34+ cells/kg to be eligible.

Transplant regimen

Patients received the BEAM (carmustine, etoposide, cytarabine, and melphalan) transplant regimen on day 0. They did not receive antiretroviral therapy from the time of the start of BEAM until 7 days after completion of the preparative regimen.

Efavirenz was held for 2 weeks prior to BEAM initiation, and an alternative agent was substituted during this time period. Zidovudine was prohibited following transplant because of its myelosuppressive effects.

Patients received growth factor, transfusion, and antimicrobial supportive care according to institutional standards of the transplant center.

Patient characteristics

Of the original 43 patients enrolled, 3 patients experienced disease progression prior to the conditioning regimen and did not undergo transplant. Therefore, investigators did not include them in the study analysis.

Forty patients received ASCT at 16 different transplant centers. They were a median age of 46.9 (range, 22.5–62.2), and 35 were male.

All patients received peripheral blood stem cell grafts at a median dose of 3.9 x 10⁶ CD34+ cells/kg (range, 1.6–11.0). And all patients were able to mobilize hematopoietic progenitor cells in a median of 2 apheresis collections (range, 1–5).

Most patients (n=32; 80%) had a pre-transplant HIV viral load that was undetectable. The median viral load for those 8 patients with detectable disease was 80 copies/mL (range, 50–17,455).

Patients had a median pre-transplant CD4+ T-cell count of 249.0 CD4+/μL (range, 39–797).

Investigators followed the patients for a median of 24.8 months (range, 2.8–27.2).

Response

Seven patients died during the follow-up period, 5 within 1 year of transplant. Four of the deaths within 1 year of transplant were due to relapse or disease progression.

One-year transplant-related mortality (TRM) was 5.2%.

The 1-year overall survival (OS) probability was 87.3%, and, at 2 years, it was 82%. The 2-year progression-free survival (PFS) was 79.8%, and the cumulative incidence of relapse/progression at 2 years was 12.5%.

The probabilities for OS and PFS at 2 years were comparable for both NHL and HL patients.

The median time to post-transplant neutrophil recovery was 11 days, and 97.5% of patients recovered their neutrophil counts by day 28.

The median time to platelet recovery was 18 days, and 92.5% of patients recovered their platelet counts by day 100.

At 100 days post-transplant, 28.9% of the evaluable patients (11/38) had recovered hematologic function. And at 1 year, 74.2% (23/31) had recovered hematologic function.

Adverse events

A little more than half (55%) the patients had at least 1 infectious event within a year of transplant, including 11 who had a severe infection.

Of the 57 infections that occurred post-transplant, 25 were due to bacteria, 22 to viruses, 6 to fungal organisms, 2 to protozoa, and 2 to other organisms. No patient developed Pneumocystis jiroveci pneumonia after transplant.

Nine patients experienced a total of 13 grade 3–5 adverse events. This included infection/sepsis (5 events), venous thromboembolism (2 events), and 1 event each for esophageal candidiasis, enteritis, hyperglycemia, hypernatremia, acute appendicitis, and acute coronary syndrome.

Sixteen patients had to be re-admitted to the hospital after the transplant, for a total of 34 readmissions. Infection (18) and fever (6) were the most common reasons for readmission.

Data comparison

The investigators compared the OS and PFS results to a control group identified through the Center for International Bone Marrow Transplant Research (CIBMTR).

One hundred fifty-one controls matched for age, performance status, primary disease, and disease status at transplant were identified for the 40 HIV-lymphoma cases.

The 1-year OS for the control group was 87.7%, and the 2-year PFS was 69.5%. This compared with the 87.3% and 79.8% for OS and PFS, respectively, for the HIV-lymphoma patients.

These results, the investigators wrote, were not significantly different from outcomes of CIBMTR controls, with a hazard ratio for overall mortality in the HIV-lymphoma patients of 0.67 (95% CI: 0.30–1.50, P=0.33) compared to controls.

And the hazard ratio for treatment failure in the HIV-lymphoma patients was 0.52 (95% CI: 0.2927–1.03, P=0.06) compared to controls.

The investigators concluded that HIV infection alone should not be considered a contraindication to ASCT for patients who otherwise meet transplant inclusion criteria. And ASCT should be considered the standard of care for patients with HIV-related lymphoma, provided that the HIV infection is treatment-responsive.

The team added that these patients should also be considered “appropriate potential participants” for future ASCT clinical trials.

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) is seeking candidates to fill three vacancies on the committee beginning in October 2016. Nominations are due Thursday, June 30.

The committee is seeking to fill the vacancies with men and women surgeons who are interested in advancing the role of women in the ACS and in encouraging and mentoring women in surgery. The committee encourages representation by individuals of diverse cultural, racial, and ethnic backgrounds.

Nominees must be ACS Fellows or Associate Fellows who are able to fulfill the following responsibilities:

• Serve an initial three-year term: 2016-2019

• Attend two in-person meetings annually – one during the ACS Leadership & Advocacy Summit in Washington, DC, in the spring, and the other at the annual ACS Clinical Congress

• Participate in quarterly conference calls

• Actively serve on one subcommittee

• Contribute to committee initiatives

Nominees should submit:

• A letter of interest highlighting their skills and expertise, along with contributions they could offer the committee

• A five-page or shorter summary of their curriculum vitae

Nominations should be submitted to Connie Bura, Associate Director, ACS Division of Member Services, at [email protected].

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) is seeking candidates to fill three vacancies on the committee beginning in October 2016. Nominations are due Thursday, June 30.

The committee is seeking to fill the vacancies with men and women surgeons who are interested in advancing the role of women in the ACS and in encouraging and mentoring women in surgery. The committee encourages representation by individuals of diverse cultural, racial, and ethnic backgrounds.

Nominees must be ACS Fellows or Associate Fellows who are able to fulfill the following responsibilities:

• Serve an initial three-year term: 2016-2019

• Attend two in-person meetings annually – one during the ACS Leadership & Advocacy Summit in Washington, DC, in the spring, and the other at the annual ACS Clinical Congress

• Participate in quarterly conference calls

• Actively serve on one subcommittee

• Contribute to committee initiatives

Nominees should submit:

• A letter of interest highlighting their skills and expertise, along with contributions they could offer the committee

• A five-page or shorter summary of their curriculum vitae

Nominations should be submitted to Connie Bura, Associate Director, ACS Division of Member Services, at [email protected].

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) is seeking candidates to fill three vacancies on the committee beginning in October 2016. Nominations are due Thursday, June 30.

The committee is seeking to fill the vacancies with men and women surgeons who are interested in advancing the role of women in the ACS and in encouraging and mentoring women in surgery. The committee encourages representation by individuals of diverse cultural, racial, and ethnic backgrounds.

Nominees must be ACS Fellows or Associate Fellows who are able to fulfill the following responsibilities:

• Serve an initial three-year term: 2016-2019

• Attend two in-person meetings annually – one during the ACS Leadership & Advocacy Summit in Washington, DC, in the spring, and the other at the annual ACS Clinical Congress

• Participate in quarterly conference calls

• Actively serve on one subcommittee

• Contribute to committee initiatives

Nominees should submit:

• A letter of interest highlighting their skills and expertise, along with contributions they could offer the committee

• A five-page or shorter summary of their curriculum vitae

Nominations should be submitted to Connie Bura, Associate Director, ACS Division of Member Services, at [email protected].

For the second consecutive year, Becker’s Hospital Review has identified Clifford Y. Ko, MD, MS, MSHS, FACS, as one of 50 experts leading the field of patient safety in the United States. Dr. Ko is Director, American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®), and Director, ACS Division of Research and Optimal Patient Care. He also is a colon and rectal surgeon and professor, University of California, Los Angeles (UCLA), Schools of Medicine and Public Health; Robert and Kelly Day Chair in Surgical Outcomes, UCLA; and a research affiliate, RAND Corp.

The 2016 edition of the Becker’s Hospital Review list includes individuals at national organizations, universities, and health care systems who are working to improve patient safety. This fourth edition includes the names of advocates, professors, researchers, administrators, and health care providers who have won awards, published articles, spoken out, and led initiatives to reduce medical injuries and ensure patient safety. The Becker’s Hospital Review editorial team considered nominations and selected leaders through an editorial review process.

View the full list of recipients on the Becker’s Hospital Review website at http://goo.gl/srQVN3. Dr. Ko’s profile appears on the website at http://goo.gl/NMUUOz.

For the second consecutive year, Becker’s Hospital Review has identified Clifford Y. Ko, MD, MS, MSHS, FACS, as one of 50 experts leading the field of patient safety in the United States. Dr. Ko is Director, American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®), and Director, ACS Division of Research and Optimal Patient Care. He also is a colon and rectal surgeon and professor, University of California, Los Angeles (UCLA), Schools of Medicine and Public Health; Robert and Kelly Day Chair in Surgical Outcomes, UCLA; and a research affiliate, RAND Corp.

The 2016 edition of the Becker’s Hospital Review list includes individuals at national organizations, universities, and health care systems who are working to improve patient safety. This fourth edition includes the names of advocates, professors, researchers, administrators, and health care providers who have won awards, published articles, spoken out, and led initiatives to reduce medical injuries and ensure patient safety. The Becker’s Hospital Review editorial team considered nominations and selected leaders through an editorial review process.

View the full list of recipients on the Becker’s Hospital Review website at http://goo.gl/srQVN3. Dr. Ko’s profile appears on the website at http://goo.gl/NMUUOz.

For the second consecutive year, Becker’s Hospital Review has identified Clifford Y. Ko, MD, MS, MSHS, FACS, as one of 50 experts leading the field of patient safety in the United States. Dr. Ko is Director, American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®), and Director, ACS Division of Research and Optimal Patient Care. He also is a colon and rectal surgeon and professor, University of California, Los Angeles (UCLA), Schools of Medicine and Public Health; Robert and Kelly Day Chair in Surgical Outcomes, UCLA; and a research affiliate, RAND Corp.

The 2016 edition of the Becker’s Hospital Review list includes individuals at national organizations, universities, and health care systems who are working to improve patient safety. This fourth edition includes the names of advocates, professors, researchers, administrators, and health care providers who have won awards, published articles, spoken out, and led initiatives to reduce medical injuries and ensure patient safety. The Becker’s Hospital Review editorial team considered nominations and selected leaders through an editorial review process.

View the full list of recipients on the Becker’s Hospital Review website at http://goo.gl/srQVN3. Dr. Ko’s profile appears on the website at http://goo.gl/NMUUOz.

Nominations for candidates to fill two vacancies on the American College of Surgeons (ACS) Committee on Diversity Issues are due Thursday, June 30, for assignments that will begin in October 2016.

The committee’s mission is to study the educational and professional needs of underrepresented surgeons and surgical trainees. In addition, committee members will study the impact that the committee’s work may have on the elimination of health care disparities among diverse population groups. Committee work will include developing proposals and sessions on diversity for the ACS Clinical Congress, and advancing tools and resources to enhance surgeons’ cultural competency.

Nominees must be ACS Fellows or Associate Fellows who are able to fulfill the following criteria:

• Serve an initial three-year term, 2016-2019

• Attend one in-person meeting at the ACS Clinical Congress and participate in regular committee conference calls

• Actively contribute to committee initiatives

Nominees should submit:

• A letter of interest highlighting their skills and expertise, along with a list of contributions they would offer the committee

• A summary of their curriculum vitae, in fewer than five pages

For additional information and to submit nominations, contact Connie Bura, Associate Director, ACS Division of Member Services, at [email protected].

Nominations for candidates to fill two vacancies on the American College of Surgeons (ACS) Committee on Diversity Issues are due Thursday, June 30, for assignments that will begin in October 2016.

The committee’s mission is to study the educational and professional needs of underrepresented surgeons and surgical trainees. In addition, committee members will study the impact that the committee’s work may have on the elimination of health care disparities among diverse population groups. Committee work will include developing proposals and sessions on diversity for the ACS Clinical Congress, and advancing tools and resources to enhance surgeons’ cultural competency.

Nominees must be ACS Fellows or Associate Fellows who are able to fulfill the following criteria:

• Serve an initial three-year term, 2016-2019

• Attend one in-person meeting at the ACS Clinical Congress and participate in regular committee conference calls

• Actively contribute to committee initiatives

Nominees should submit:

• A letter of interest highlighting their skills and expertise, along with a list of contributions they would offer the committee

• A summary of their curriculum vitae, in fewer than five pages

For additional information and to submit nominations, contact Connie Bura, Associate Director, ACS Division of Member Services, at [email protected].

Nominations for candidates to fill two vacancies on the American College of Surgeons (ACS) Committee on Diversity Issues are due Thursday, June 30, for assignments that will begin in October 2016.

The committee’s mission is to study the educational and professional needs of underrepresented surgeons and surgical trainees. In addition, committee members will study the impact that the committee’s work may have on the elimination of health care disparities among diverse population groups. Committee work will include developing proposals and sessions on diversity for the ACS Clinical Congress, and advancing tools and resources to enhance surgeons’ cultural competency.

Nominees must be ACS Fellows or Associate Fellows who are able to fulfill the following criteria:

• Serve an initial three-year term, 2016-2019

• Attend one in-person meeting at the ACS Clinical Congress and participate in regular committee conference calls

• Actively contribute to committee initiatives

Nominees should submit:

• A letter of interest highlighting their skills and expertise, along with a list of contributions they would offer the committee

• A summary of their curriculum vitae, in fewer than five pages

For additional information and to submit nominations, contact Connie Bura, Associate Director, ACS Division of Member Services, at [email protected].

Applications for the American College of Surgeons (ACS) Mentorship Program for Women Surgeons are due Friday, July 15. Through this program early-career female surgeons develop a mentoring relationship with established surgeons representing all specialties of the ACS.

This year’s mentoring program, October 2016 through October 2017, will include up to 25 mentor/mentee pairs who must attend the ACS Clinical Congress 2016, Oct. 16-20 in Washington, D.C. Applicants must be ACS Fellows or Associate Fellows, or in the process of applying for ACS Fellowship.

The committee also seeks qualified mentors. Visit the Women in Surgery Committee (WiSC) webpage (https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities) to download the mentor or mentee application. All applicants will receive notification by Aug. 30 regarding their participation in the program.

Find more information about the WiSC on its webpage at https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities. Submit applications to Connie Bura, Associate Director, Division of Member Services, at [email protected].

Applications for the American College of Surgeons (ACS) Mentorship Program for Women Surgeons are due Friday, July 15. Through this program early-career female surgeons develop a mentoring relationship with established surgeons representing all specialties of the ACS.

This year’s mentoring program, October 2016 through October 2017, will include up to 25 mentor/mentee pairs who must attend the ACS Clinical Congress 2016, Oct. 16-20 in Washington, D.C. Applicants must be ACS Fellows or Associate Fellows, or in the process of applying for ACS Fellowship.

The committee also seeks qualified mentors. Visit the Women in Surgery Committee (WiSC) webpage (https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities) to download the mentor or mentee application. All applicants will receive notification by Aug. 30 regarding their participation in the program.

Find more information about the WiSC on its webpage at https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities. Submit applications to Connie Bura, Associate Director, Division of Member Services, at [email protected].

Applications for the American College of Surgeons (ACS) Mentorship Program for Women Surgeons are due Friday, July 15. Through this program early-career female surgeons develop a mentoring relationship with established surgeons representing all specialties of the ACS.

This year’s mentoring program, October 2016 through October 2017, will include up to 25 mentor/mentee pairs who must attend the ACS Clinical Congress 2016, Oct. 16-20 in Washington, D.C. Applicants must be ACS Fellows or Associate Fellows, or in the process of applying for ACS Fellowship.

The committee also seeks qualified mentors. Visit the Women in Surgery Committee (WiSC) webpage (https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities) to download the mentor or mentee application. All applicants will receive notification by Aug. 30 regarding their participation in the program.

Find more information about the WiSC on its webpage at https://www.facs.org/about-acs/governance/acs-committees/women-in-surgery-committee/activities. Submit applications to Connie Bura, Associate Director, Division of Member Services, at [email protected].

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) is accepting nominations through Thursday, June 30, for a new annual award, the Mary Edwards Walker Inspiring Women in Surgery Award. The award, which will be presented at Clinical Congress 2016, honors the work of Mary Edwards Walker (1832-1919) the first female surgeon employed by the U.S. Army and the only woman ever to receive the Medal of Honor, the highest U.S. Armed Forces decoration for bravery.

Nominees must be ACS members, either in active practice or retired, who meet the following requirements:

• A demonstrated commitment to the advancement and inspiration of women in surgery.

• Current WiSC members are ineligible for this award.

• The awardee is expected to attend the ACS Clinical Congress 2016 in Washington, DC, to accept the award.

Nominations must include a letter of nomination outlining how the nominee has contributed to the advancement of women in surgery and the nominee’s current curriculum vitae. Self-nominations are acceptable and should include a letter of reference. E-mail all materials to Connie Bura, ACS Associate Director, Division of Member Services, at [email protected]. Contact Ms. Bura for additional information.

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) is accepting nominations through Thursday, June 30, for a new annual award, the Mary Edwards Walker Inspiring Women in Surgery Award. The award, which will be presented at Clinical Congress 2016, honors the work of Mary Edwards Walker (1832-1919) the first female surgeon employed by the U.S. Army and the only woman ever to receive the Medal of Honor, the highest U.S. Armed Forces decoration for bravery.

Nominees must be ACS members, either in active practice or retired, who meet the following requirements:

• A demonstrated commitment to the advancement and inspiration of women in surgery.

• Current WiSC members are ineligible for this award.

• The awardee is expected to attend the ACS Clinical Congress 2016 in Washington, DC, to accept the award.

Nominations must include a letter of nomination outlining how the nominee has contributed to the advancement of women in surgery and the nominee’s current curriculum vitae. Self-nominations are acceptable and should include a letter of reference. E-mail all materials to Connie Bura, ACS Associate Director, Division of Member Services, at [email protected]. Contact Ms. Bura for additional information.

The American College of Surgeons (ACS) Women in Surgery Committee (WiSC) is accepting nominations through Thursday, June 30, for a new annual award, the Mary Edwards Walker Inspiring Women in Surgery Award. The award, which will be presented at Clinical Congress 2016, honors the work of Mary Edwards Walker (1832-1919) the first female surgeon employed by the U.S. Army and the only woman ever to receive the Medal of Honor, the highest U.S. Armed Forces decoration for bravery.

Nominees must be ACS members, either in active practice or retired, who meet the following requirements:

• A demonstrated commitment to the advancement and inspiration of women in surgery.

• Current WiSC members are ineligible for this award.

• The awardee is expected to attend the ACS Clinical Congress 2016 in Washington, DC, to accept the award.

Nominations must include a letter of nomination outlining how the nominee has contributed to the advancement of women in surgery and the nominee’s current curriculum vitae. Self-nominations are acceptable and should include a letter of reference. E-mail all materials to Connie Bura, ACS Associate Director, Division of Member Services, at [email protected]. Contact Ms. Bura for additional information.