Columbia/Paul Joseph

A medication used to treat joint and skin conditions might also improve allogeneic hematopoietic stem cell transplant (HSCT), according to research published in Science Translational Medicine.

Researchers discovered that, once transplanted, some differentiated cells produce tumor necrosis factor-alpha (TNFα), which impairs cell division and survival of hematopoietic stem and progenitor cells (HSPCs).

This led the researchers to explore whether a drug that blocks TNFα would allow HSPCs to thrive in a new host.

The team administered etanercept, an antibody that binds to and disables TNFα, to mice receiving umbilical cord blood (UCB) transplants.

Mice that received the drug had better bone marrow reconstitution than control mice.

“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” said study author Peter Zandstra, PhD, of the University of British Columbia in Vancouver, British Columbia, Canada.

“That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible, not only for blood cancers, which we are already doing, but also for auto-immune diseases, like Crohn’s disease, even HIV.”

Dr Zandstra and his colleagues began this research by performing UCB transplants in immunodeficient mice.

The team was surprised to find that mice receiving the highest numbers of UCB cells had the worst outcomes in terms of bone marrow reconstitution. The researchers also found elevated levels of cytokines in the animals’ sera.

The team speculated that mature immune cells within UCB might be producing inflammatory cytokines, thus preventing HSPCs from successfully repopulating the bone marrow.

One molecule in particular, TNFα, inhibited HSPC survival and division.

Treating recipient mice with the TNFα blocker etanercept enhanced short-term HSPC engraftment and accelerated hematopoietic recovery after UCB transplants.

According to the researchers, these results implicate TNFα as a central player in setting off the cytokine storm that can impair donor HSPC survival.

The team also believes their results provide a strong basis for conducting a clinical trial to see whether etanercept or another TNFα blocker would improve outcomes for people receiving HSCTs.

“Failure of the graft after stem cell transplantation is always a potentially life-threatening complication,” said Kirk Schultz, MD, a professor at the University of British Columbia who was not involved in this study.

“This is especially the case when we must use mismatched stem cells derived from umbilical cord blood. This advance may offer a significant advance in making these transplants more successful.”

Columbia/Paul Joseph

A medication used to treat joint and skin conditions might also improve allogeneic hematopoietic stem cell transplant (HSCT), according to research published in Science Translational Medicine.

Researchers discovered that, once transplanted, some differentiated cells produce tumor necrosis factor-alpha (TNFα), which impairs cell division and survival of hematopoietic stem and progenitor cells (HSPCs).

This led the researchers to explore whether a drug that blocks TNFα would allow HSPCs to thrive in a new host.

The team administered etanercept, an antibody that binds to and disables TNFα, to mice receiving umbilical cord blood (UCB) transplants.

Mice that received the drug had better bone marrow reconstitution than control mice.

“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” said study author Peter Zandstra, PhD, of the University of British Columbia in Vancouver, British Columbia, Canada.

“That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible, not only for blood cancers, which we are already doing, but also for auto-immune diseases, like Crohn’s disease, even HIV.”

Dr Zandstra and his colleagues began this research by performing UCB transplants in immunodeficient mice.

The team was surprised to find that mice receiving the highest numbers of UCB cells had the worst outcomes in terms of bone marrow reconstitution. The researchers also found elevated levels of cytokines in the animals’ sera.

The team speculated that mature immune cells within UCB might be producing inflammatory cytokines, thus preventing HSPCs from successfully repopulating the bone marrow.

One molecule in particular, TNFα, inhibited HSPC survival and division.

Treating recipient mice with the TNFα blocker etanercept enhanced short-term HSPC engraftment and accelerated hematopoietic recovery after UCB transplants.

According to the researchers, these results implicate TNFα as a central player in setting off the cytokine storm that can impair donor HSPC survival.

The team also believes their results provide a strong basis for conducting a clinical trial to see whether etanercept or another TNFα blocker would improve outcomes for people receiving HSCTs.

“Failure of the graft after stem cell transplantation is always a potentially life-threatening complication,” said Kirk Schultz, MD, a professor at the University of British Columbia who was not involved in this study.

“This is especially the case when we must use mismatched stem cells derived from umbilical cord blood. This advance may offer a significant advance in making these transplants more successful.”

Columbia/Paul Joseph

A medication used to treat joint and skin conditions might also improve allogeneic hematopoietic stem cell transplant (HSCT), according to research published in Science Translational Medicine.

Researchers discovered that, once transplanted, some differentiated cells produce tumor necrosis factor-alpha (TNFα), which impairs cell division and survival of hematopoietic stem and progenitor cells (HSPCs).

This led the researchers to explore whether a drug that blocks TNFα would allow HSPCs to thrive in a new host.

The team administered etanercept, an antibody that binds to and disables TNFα, to mice receiving umbilical cord blood (UCB) transplants.

Mice that received the drug had better bone marrow reconstitution than control mice.

“If this strategy boosts the survival rate of blood stem cells in humans, then we can get away with using smaller grafts,” said study author Peter Zandstra, PhD, of the University of British Columbia in Vancouver, British Columbia, Canada.

“That would vastly increase the pool of usable umbilical cord blood donations, making stem cell transplants more feasible, not only for blood cancers, which we are already doing, but also for auto-immune diseases, like Crohn’s disease, even HIV.”

Dr Zandstra and his colleagues began this research by performing UCB transplants in immunodeficient mice.

The team was surprised to find that mice receiving the highest numbers of UCB cells had the worst outcomes in terms of bone marrow reconstitution. The researchers also found elevated levels of cytokines in the animals’ sera.

The team speculated that mature immune cells within UCB might be producing inflammatory cytokines, thus preventing HSPCs from successfully repopulating the bone marrow.

One molecule in particular, TNFα, inhibited HSPC survival and division.

Treating recipient mice with the TNFα blocker etanercept enhanced short-term HSPC engraftment and accelerated hematopoietic recovery after UCB transplants.

According to the researchers, these results implicate TNFα as a central player in setting off the cytokine storm that can impair donor HSPC survival.

The team also believes their results provide a strong basis for conducting a clinical trial to see whether etanercept or another TNFα blocker would improve outcomes for people receiving HSCTs.

“Failure of the graft after stem cell transplantation is always a potentially life-threatening complication,” said Kirk Schultz, MD, a professor at the University of British Columbia who was not involved in this study.

“This is especially the case when we must use mismatched stem cells derived from umbilical cord blood. This advance may offer a significant advance in making these transplants more successful.”

Clinical question: What is the content and structure of patient care–related text paging sent in the inpatient setting?

Background: Text paging has become a common form of communication among members of the inpatient multidisciplinary team, but there are potential risks and downsides of text paging, including disruptiveness, inefficiency, and potential patient safety issues.

Study Design: Modified case-study approach.

Setting: The medical inpatient service of an academic tertiary care hospital.

Synopsis: 575 text-page messages relating to 217 unique patients were analyzed in the study. The majority of the messages were sent from nonphysicians to physicians. Common themes that were identified included lack of standardization of textmessage content and format, lack of indicators of the urgency of the message, and lack of clarity within the message. Pertinent information sometimes was missing from the messages, and it was not always clear whether the sender was requesting a response from the recipient.

Bottom line: Text-paging practices may raise patient safety issues that could be addressed by implementation of a standardized, structured approach to this form of communication.

Citation: Luxenberg A et al. Efficiency and interpretability of text paging communication for medical inpatients: A mixed-methods analysis. JAMA Intern Med. 2017;177(8):1218-20.

Dr. Wachter is an assistant professor of medicine at Duke University

Clinical question: What is the content and structure of patient care–related text paging sent in the inpatient setting?

Background: Text paging has become a common form of communication among members of the inpatient multidisciplinary team, but there are potential risks and downsides of text paging, including disruptiveness, inefficiency, and potential patient safety issues.

Study Design: Modified case-study approach.

Setting: The medical inpatient service of an academic tertiary care hospital.

Synopsis: 575 text-page messages relating to 217 unique patients were analyzed in the study. The majority of the messages were sent from nonphysicians to physicians. Common themes that were identified included lack of standardization of textmessage content and format, lack of indicators of the urgency of the message, and lack of clarity within the message. Pertinent information sometimes was missing from the messages, and it was not always clear whether the sender was requesting a response from the recipient.

Bottom line: Text-paging practices may raise patient safety issues that could be addressed by implementation of a standardized, structured approach to this form of communication.

Citation: Luxenberg A et al. Efficiency and interpretability of text paging communication for medical inpatients: A mixed-methods analysis. JAMA Intern Med. 2017;177(8):1218-20.

Dr. Wachter is an assistant professor of medicine at Duke University

Clinical question: What is the content and structure of patient care–related text paging sent in the inpatient setting?

Background: Text paging has become a common form of communication among members of the inpatient multidisciplinary team, but there are potential risks and downsides of text paging, including disruptiveness, inefficiency, and potential patient safety issues.

Study Design: Modified case-study approach.

Setting: The medical inpatient service of an academic tertiary care hospital.

Synopsis: 575 text-page messages relating to 217 unique patients were analyzed in the study. The majority of the messages were sent from nonphysicians to physicians. Common themes that were identified included lack of standardization of textmessage content and format, lack of indicators of the urgency of the message, and lack of clarity within the message. Pertinent information sometimes was missing from the messages, and it was not always clear whether the sender was requesting a response from the recipient.

Bottom line: Text-paging practices may raise patient safety issues that could be addressed by implementation of a standardized, structured approach to this form of communication.

Citation: Luxenberg A et al. Efficiency and interpretability of text paging communication for medical inpatients: A mixed-methods analysis. JAMA Intern Med. 2017;177(8):1218-20.

Dr. Wachter is an assistant professor of medicine at Duke University

Photo courtesy of Amgen

Treatment with the proteasome inhibitor carfilzomib is associated with a “significant incidence” of cardiovascular adverse events (CVAEs) in patients with multiple myeloma (MM), according to researchers.

An analysis of 24 studies showed that 18% of MM patients receiving carfilzomib had CVAEs, and 8% had grade 3 or higher CVAEs.

The relative risk of CVAEs (all-grade or high-grade) was higher among patients who received carfilzomib than among those who did not.

These findings were published in JAMA Oncology.

The researchers gathered data from 24 studies reported from 2007 through 2017. The studies included 2594 MM patients.

The team looked at the incidence of CVAEs, which included heart failure, hypertension, ischemia, and arrhythmia.

The data showed that 18.1% of patients who took carfilzomib experienced CVAEs, and 8.2% of the patients had grade 3 or higher CVAEs.

For comparison, a similar review of bortezomib showed that 3.8% of patients experienced CVAEs, and 2.3% of patients had high-grade CVAEs.

Among the carfilzomib-treated patients, the most common CVAE was hypertension (12.2%), followed by heart failure (4.1%), arrhythmias (2.4%), and ischemic events (1.8%).

Higher doses of carfilzomib were associated with higher rates of high-grade CVAEs. The incidence of high-grade CVAEs was 6.4% in patients who received carfilzomib doses below 45 mg/m² and 11.9% in patients who received the drug at doses of 45 mg/m² or higher (P=0.02).

The researchers also compared CVAE rates in carfilzomib-treated patients and non-carfilzomib-treated patients enrolled in a trio of phase 3, randomized trials:

• ASPIRE (carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone)
• ENDEAVOR (carfilzomib and dexamethasone vs bortezomib and dexamethasone)
• FOCUS (carfilzomib and dexamethasone vs dexamethasone with or without cyclophosphamide).

The relative risk of all-grade CVAEs was 1.8 for carfilzomib-treated patients vs controls (P<0.001), and the relative risk of grade 3 or higher CVAEs was 2.2 (P<0.001).

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” said study author Adam J. Waxman, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly.”

Dr Waxman and his colleagues also called for further clinical trials to evaluate the association between carfilzomib and CVAEs, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr Waxman said.

This research was supported by the National Institutes of Health (T32-GM075766).

Photo courtesy of Amgen

Treatment with the proteasome inhibitor carfilzomib is associated with a “significant incidence” of cardiovascular adverse events (CVAEs) in patients with multiple myeloma (MM), according to researchers.

An analysis of 24 studies showed that 18% of MM patients receiving carfilzomib had CVAEs, and 8% had grade 3 or higher CVAEs.

The relative risk of CVAEs (all-grade or high-grade) was higher among patients who received carfilzomib than among those who did not.

These findings were published in JAMA Oncology.

The researchers gathered data from 24 studies reported from 2007 through 2017. The studies included 2594 MM patients.

The team looked at the incidence of CVAEs, which included heart failure, hypertension, ischemia, and arrhythmia.

The data showed that 18.1% of patients who took carfilzomib experienced CVAEs, and 8.2% of the patients had grade 3 or higher CVAEs.

For comparison, a similar review of bortezomib showed that 3.8% of patients experienced CVAEs, and 2.3% of patients had high-grade CVAEs.

Among the carfilzomib-treated patients, the most common CVAE was hypertension (12.2%), followed by heart failure (4.1%), arrhythmias (2.4%), and ischemic events (1.8%).

Higher doses of carfilzomib were associated with higher rates of high-grade CVAEs. The incidence of high-grade CVAEs was 6.4% in patients who received carfilzomib doses below 45 mg/m² and 11.9% in patients who received the drug at doses of 45 mg/m² or higher (P=0.02).

The researchers also compared CVAE rates in carfilzomib-treated patients and non-carfilzomib-treated patients enrolled in a trio of phase 3, randomized trials:

• ASPIRE (carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone)
• ENDEAVOR (carfilzomib and dexamethasone vs bortezomib and dexamethasone)
• FOCUS (carfilzomib and dexamethasone vs dexamethasone with or without cyclophosphamide).

The relative risk of all-grade CVAEs was 1.8 for carfilzomib-treated patients vs controls (P<0.001), and the relative risk of grade 3 or higher CVAEs was 2.2 (P<0.001).

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” said study author Adam J. Waxman, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly.”

Dr Waxman and his colleagues also called for further clinical trials to evaluate the association between carfilzomib and CVAEs, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr Waxman said.

This research was supported by the National Institutes of Health (T32-GM075766).

Photo courtesy of Amgen

Treatment with the proteasome inhibitor carfilzomib is associated with a “significant incidence” of cardiovascular adverse events (CVAEs) in patients with multiple myeloma (MM), according to researchers.

An analysis of 24 studies showed that 18% of MM patients receiving carfilzomib had CVAEs, and 8% had grade 3 or higher CVAEs.

The relative risk of CVAEs (all-grade or high-grade) was higher among patients who received carfilzomib than among those who did not.

These findings were published in JAMA Oncology.

The researchers gathered data from 24 studies reported from 2007 through 2017. The studies included 2594 MM patients.

The team looked at the incidence of CVAEs, which included heart failure, hypertension, ischemia, and arrhythmia.

The data showed that 18.1% of patients who took carfilzomib experienced CVAEs, and 8.2% of the patients had grade 3 or higher CVAEs.

For comparison, a similar review of bortezomib showed that 3.8% of patients experienced CVAEs, and 2.3% of patients had high-grade CVAEs.

Among the carfilzomib-treated patients, the most common CVAE was hypertension (12.2%), followed by heart failure (4.1%), arrhythmias (2.4%), and ischemic events (1.8%).

Higher doses of carfilzomib were associated with higher rates of high-grade CVAEs. The incidence of high-grade CVAEs was 6.4% in patients who received carfilzomib doses below 45 mg/m² and 11.9% in patients who received the drug at doses of 45 mg/m² or higher (P=0.02).

The researchers also compared CVAE rates in carfilzomib-treated patients and non-carfilzomib-treated patients enrolled in a trio of phase 3, randomized trials:

• ASPIRE (carfilzomib, lenalidomide, and dexamethasone vs lenalidomide and dexamethasone)
• ENDEAVOR (carfilzomib and dexamethasone vs bortezomib and dexamethasone)
• FOCUS (carfilzomib and dexamethasone vs dexamethasone with or without cyclophosphamide).

The relative risk of all-grade CVAEs was 1.8 for carfilzomib-treated patients vs controls (P<0.001), and the relative risk of grade 3 or higher CVAEs was 2.2 (P<0.001).

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” said study author Adam J. Waxman, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly.”

Dr Waxman and his colleagues also called for further clinical trials to evaluate the association between carfilzomib and CVAEs, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr Waxman said.

This research was supported by the National Institutes of Health (T32-GM075766).

Early furosemide treatment associated with decrease in hospital mortality for acute heart failure

Early furosemide treatment associated with decrease in hospital mortality for acute heart failure

Early furosemide treatment associated with decrease in hospital mortality for acute heart failure

© Phil McCarten 2017

ATLANTA—The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) is showing consistent, ongoing responses more than a year after infusion.

An updated analysis of the phase 1/2 ZUMA-1 trial showed that 42% of patients who received axi-cel maintained an objective response at a median follow-up of 15.4 months.

Forty percent of patients have maintained a complete response (CR).

This compares with a 44% objective response rate and a 39% CR rate in the primary analysis of phase 2 ZUMA-1 data, when the median follow-up was 8.7 months.

Sattva S. Neelapu, MD, of MD Anderson Cancer Center in Houston, Texas, reported the long-term results from ZUMA-1 at the 2017 ASH Annual Meeting (abstract 578). The findings were published simultaneously in NEJM.

The primary phase 2 analysis was previously presented at the AACR Annual Meeting 2017.

At ASH 2017, Dr Neelapu disclosed that he has received research funding and served as a consultant for Kite Pharma, the developer of axi-cel. Kite Pharma and the Leukemia & Lymphoma Society Therapy Acceleration Program supported ZUMA-1.

Study schema and patient characteristics

Phase 1 of ZUMA-1 enrolled 7 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL).

In phase 2, 101 patients were grouped into 2 cohorts—77 with refractory DLBCL and 24 with refractory PMBCL/TFL.

A total of 108 patients were treated in phases 1 and 2 and were included in the long-term pooled analysis.

Patients received a conditioning regimen of cyclophosphamide and fludarabine and, 2 days later, a fixed dose of axi-cel at 2 x 10⁶ CAR T cells/kg.

“Importantly, the product could be manufactured for 99% of enrolled patients,” Dr Neelapu said. “Moreover, 91% of the enrolled patients were dosed with axi-cel, and there were no patients lost to follow-up.”

Patients in the pooled analysis were a median age of 58 (range, 23–76), and 27 (25%) were 65 or older.

Seventy-three patients (68%) were male, 62 (57%) had an ECOG status of 1, 90 (83%) had stage III or IV disease, and 48 (44%) had an IPI score of 3 to 4.

Seventy-six patients (70%) had received 3 or more prior therapies.

Eighty patients (74%) were refractory to their second or later line of therapy, and 70 (65%) had progressive disease as their best response to their last prior therapy. Twenty-five patients (23%) had relapsed after autologous stem cell transplant.

Response

The data cutoff for the long-term analysis was August 11, 2017.

In addition to the ongoing responses mentioned above, the best objective response was 82% in both the phase 2 primary analysis and the long-term analysis for phases 1 and 2.

CR as the best objective response increased from 54% in the primary analysis to 58% at the longer follow-up.

“We did observe deepening of the responses over time,” Dr Neelapu said. “At the time of the first tumor assessment, 60 patients had either partial remission or stable disease. But 23 of those 60 eventually achieved a complete remission up to 15 months post-infusion without any additional therapy.”

The median time to conversion from partial response to CR was 64 days (range, 49–242).

“The durability of these responses was observed consistently across key covariates,” Dr Neelapu added, “including the refractory subgroups, the disease stage groups, IPI risk groups. The CD19 status at baseline did not matter, nor did the cell of origin, or the CD4/CD8 ratio of the product.”

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.

© Phil McCarten 2017

ATLANTA—The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) is showing consistent, ongoing responses more than a year after infusion.

An updated analysis of the phase 1/2 ZUMA-1 trial showed that 42% of patients who received axi-cel maintained an objective response at a median follow-up of 15.4 months.

Forty percent of patients have maintained a complete response (CR).

This compares with a 44% objective response rate and a 39% CR rate in the primary analysis of phase 2 ZUMA-1 data, when the median follow-up was 8.7 months.

Sattva S. Neelapu, MD, of MD Anderson Cancer Center in Houston, Texas, reported the long-term results from ZUMA-1 at the 2017 ASH Annual Meeting (abstract 578). The findings were published simultaneously in NEJM.

The primary phase 2 analysis was previously presented at the AACR Annual Meeting 2017.

At ASH 2017, Dr Neelapu disclosed that he has received research funding and served as a consultant for Kite Pharma, the developer of axi-cel. Kite Pharma and the Leukemia & Lymphoma Society Therapy Acceleration Program supported ZUMA-1.

Study schema and patient characteristics

Phase 1 of ZUMA-1 enrolled 7 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL).

In phase 2, 101 patients were grouped into 2 cohorts—77 with refractory DLBCL and 24 with refractory PMBCL/TFL.

A total of 108 patients were treated in phases 1 and 2 and were included in the long-term pooled analysis.

Patients received a conditioning regimen of cyclophosphamide and fludarabine and, 2 days later, a fixed dose of axi-cel at 2 x 10⁶ CAR T cells/kg.

“Importantly, the product could be manufactured for 99% of enrolled patients,” Dr Neelapu said. “Moreover, 91% of the enrolled patients were dosed with axi-cel, and there were no patients lost to follow-up.”

Patients in the pooled analysis were a median age of 58 (range, 23–76), and 27 (25%) were 65 or older.

Seventy-three patients (68%) were male, 62 (57%) had an ECOG status of 1, 90 (83%) had stage III or IV disease, and 48 (44%) had an IPI score of 3 to 4.

Seventy-six patients (70%) had received 3 or more prior therapies.

Eighty patients (74%) were refractory to their second or later line of therapy, and 70 (65%) had progressive disease as their best response to their last prior therapy. Twenty-five patients (23%) had relapsed after autologous stem cell transplant.

Response

The data cutoff for the long-term analysis was August 11, 2017.

In addition to the ongoing responses mentioned above, the best objective response was 82% in both the phase 2 primary analysis and the long-term analysis for phases 1 and 2.

CR as the best objective response increased from 54% in the primary analysis to 58% at the longer follow-up.

“We did observe deepening of the responses over time,” Dr Neelapu said. “At the time of the first tumor assessment, 60 patients had either partial remission or stable disease. But 23 of those 60 eventually achieved a complete remission up to 15 months post-infusion without any additional therapy.”

The median time to conversion from partial response to CR was 64 days (range, 49–242).

“The durability of these responses was observed consistently across key covariates,” Dr Neelapu added, “including the refractory subgroups, the disease stage groups, IPI risk groups. The CD19 status at baseline did not matter, nor did the cell of origin, or the CD4/CD8 ratio of the product.”

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.

© Phil McCarten 2017

ATLANTA—The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) is showing consistent, ongoing responses more than a year after infusion.

An updated analysis of the phase 1/2 ZUMA-1 trial showed that 42% of patients who received axi-cel maintained an objective response at a median follow-up of 15.4 months.

Forty percent of patients have maintained a complete response (CR).

This compares with a 44% objective response rate and a 39% CR rate in the primary analysis of phase 2 ZUMA-1 data, when the median follow-up was 8.7 months.

Sattva S. Neelapu, MD, of MD Anderson Cancer Center in Houston, Texas, reported the long-term results from ZUMA-1 at the 2017 ASH Annual Meeting (abstract 578). The findings were published simultaneously in NEJM.

The primary phase 2 analysis was previously presented at the AACR Annual Meeting 2017.

At ASH 2017, Dr Neelapu disclosed that he has received research funding and served as a consultant for Kite Pharma, the developer of axi-cel. Kite Pharma and the Leukemia & Lymphoma Society Therapy Acceleration Program supported ZUMA-1.

Study schema and patient characteristics

Phase 1 of ZUMA-1 enrolled 7 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL).

In phase 2, 101 patients were grouped into 2 cohorts—77 with refractory DLBCL and 24 with refractory PMBCL/TFL.

A total of 108 patients were treated in phases 1 and 2 and were included in the long-term pooled analysis.

Patients received a conditioning regimen of cyclophosphamide and fludarabine and, 2 days later, a fixed dose of axi-cel at 2 x 10⁶ CAR T cells/kg.

“Importantly, the product could be manufactured for 99% of enrolled patients,” Dr Neelapu said. “Moreover, 91% of the enrolled patients were dosed with axi-cel, and there were no patients lost to follow-up.”

Patients in the pooled analysis were a median age of 58 (range, 23–76), and 27 (25%) were 65 or older.

Seventy-three patients (68%) were male, 62 (57%) had an ECOG status of 1, 90 (83%) had stage III or IV disease, and 48 (44%) had an IPI score of 3 to 4.

Seventy-six patients (70%) had received 3 or more prior therapies.

Eighty patients (74%) were refractory to their second or later line of therapy, and 70 (65%) had progressive disease as their best response to their last prior therapy. Twenty-five patients (23%) had relapsed after autologous stem cell transplant.

Response

The data cutoff for the long-term analysis was August 11, 2017.

In addition to the ongoing responses mentioned above, the best objective response was 82% in both the phase 2 primary analysis and the long-term analysis for phases 1 and 2.

CR as the best objective response increased from 54% in the primary analysis to 58% at the longer follow-up.

“We did observe deepening of the responses over time,” Dr Neelapu said. “At the time of the first tumor assessment, 60 patients had either partial remission or stable disease. But 23 of those 60 eventually achieved a complete remission up to 15 months post-infusion without any additional therapy.”

The median time to conversion from partial response to CR was 64 days (range, 49–242).

“The durability of these responses was observed consistently across key covariates,” Dr Neelapu added, “including the refractory subgroups, the disease stage groups, IPI risk groups. The CD19 status at baseline did not matter, nor did the cell of origin, or the CD4/CD8 ratio of the product.”

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.

The American Academy of Pediatrics Committee on Infectious Diseases has added information on peramivir, a recently approved antiviral medication, to its Recommendations for Prevention and Control of Influenza in Children for 2017-2018.

Peramivir (Rapivab) was approved by the Food and Drug Administration in September 2017, as an intravenous treatment for acute, uncomplicated influenza in nonhospitalized children aged 2 years and older who have been symptomatic for no more than 2 days, according to the update.

Peramivir is given to 2-12 year olds as a single infusion at 12 mg/kg, with a maximum dose of 600 mg, according to the guideline update (Pediatrics. 2017 Oct;140[4]:e20172550). Patients 13 years and older should receive the 600-mg dose.

“Rapivab is a great addition to our armamentarium of antiviral agents to combat influenza,” John A. Vanchiere, MD, PhD, chief of the section of pediatric infectious diseases at LSU Health Sciences Center, Shreveport. said in a press release from the drug’s manufacturer, BioCryst Pharmaceuticals. “It will be especially helpful for patients who cannot tolerate oral medications. In addition, the long half-life allows for one-time dosing, which will improve compliance.”

Dr. Vanchiere is the lead author in a study of peramivir’s effectiveness against pediatric influenza that was presented as a poster at ID Week 2017.

The phase 3, randomized, control trial included 122 patients, ranging in age from newborns to 18-year-olds, with acute uncomplicated influenza symptoms.

Investigators gave 92 patients peramivir, while the remaining 23 received oral oseltamivir (Tamiflu).

Nearly all (93%) of the patients were white; 61% had an influenza A strain infection, and there were comparable numbers of male and female study subjects.

Vomiting, fever, and tympanic membrane erythema were the most common adverse effects specifically reported in the study, which was funded by BioCryst.

Peramivir is the third neuraminidase inhibitor (NAI) to be approved; other approved NAIs include oral oseltamivir and inhaled zanamivir.

A fourth NAI, intravenous zanamivir, is still investigational in the United States.

Peramivir, like other antiviral drugs, may interfere with a live attenuated influenza vaccine and should not be used within 2 weeks after or 48 hours before the use of an LAIV.

While the AAP’s recommendations highlight the antiviral’s effectiveness in controlling influenza, the Academy warns that antivirals are not a substitute for influenza vaccination.

[email protected]

The American Academy of Pediatrics Committee on Infectious Diseases has added information on peramivir, a recently approved antiviral medication, to its Recommendations for Prevention and Control of Influenza in Children for 2017-2018.

Peramivir (Rapivab) was approved by the Food and Drug Administration in September 2017, as an intravenous treatment for acute, uncomplicated influenza in nonhospitalized children aged 2 years and older who have been symptomatic for no more than 2 days, according to the update.

Peramivir is given to 2-12 year olds as a single infusion at 12 mg/kg, with a maximum dose of 600 mg, according to the guideline update (Pediatrics. 2017 Oct;140[4]:e20172550). Patients 13 years and older should receive the 600-mg dose.

“Rapivab is a great addition to our armamentarium of antiviral agents to combat influenza,” John A. Vanchiere, MD, PhD, chief of the section of pediatric infectious diseases at LSU Health Sciences Center, Shreveport. said in a press release from the drug’s manufacturer, BioCryst Pharmaceuticals. “It will be especially helpful for patients who cannot tolerate oral medications. In addition, the long half-life allows for one-time dosing, which will improve compliance.”

Dr. Vanchiere is the lead author in a study of peramivir’s effectiveness against pediatric influenza that was presented as a poster at ID Week 2017.

The phase 3, randomized, control trial included 122 patients, ranging in age from newborns to 18-year-olds, with acute uncomplicated influenza symptoms.

Investigators gave 92 patients peramivir, while the remaining 23 received oral oseltamivir (Tamiflu).

Nearly all (93%) of the patients were white; 61% had an influenza A strain infection, and there were comparable numbers of male and female study subjects.

Vomiting, fever, and tympanic membrane erythema were the most common adverse effects specifically reported in the study, which was funded by BioCryst.

Peramivir is the third neuraminidase inhibitor (NAI) to be approved; other approved NAIs include oral oseltamivir and inhaled zanamivir.

A fourth NAI, intravenous zanamivir, is still investigational in the United States.

Peramivir, like other antiviral drugs, may interfere with a live attenuated influenza vaccine and should not be used within 2 weeks after or 48 hours before the use of an LAIV.

While the AAP’s recommendations highlight the antiviral’s effectiveness in controlling influenza, the Academy warns that antivirals are not a substitute for influenza vaccination.

[email protected]

The American Academy of Pediatrics Committee on Infectious Diseases has added information on peramivir, a recently approved antiviral medication, to its Recommendations for Prevention and Control of Influenza in Children for 2017-2018.

Peramivir (Rapivab) was approved by the Food and Drug Administration in September 2017, as an intravenous treatment for acute, uncomplicated influenza in nonhospitalized children aged 2 years and older who have been symptomatic for no more than 2 days, according to the update.

Peramivir is given to 2-12 year olds as a single infusion at 12 mg/kg, with a maximum dose of 600 mg, according to the guideline update (Pediatrics. 2017 Oct;140[4]:e20172550). Patients 13 years and older should receive the 600-mg dose.

“Rapivab is a great addition to our armamentarium of antiviral agents to combat influenza,” John A. Vanchiere, MD, PhD, chief of the section of pediatric infectious diseases at LSU Health Sciences Center, Shreveport. said in a press release from the drug’s manufacturer, BioCryst Pharmaceuticals. “It will be especially helpful for patients who cannot tolerate oral medications. In addition, the long half-life allows for one-time dosing, which will improve compliance.”

Dr. Vanchiere is the lead author in a study of peramivir’s effectiveness against pediatric influenza that was presented as a poster at ID Week 2017.

The phase 3, randomized, control trial included 122 patients, ranging in age from newborns to 18-year-olds, with acute uncomplicated influenza symptoms.

Investigators gave 92 patients peramivir, while the remaining 23 received oral oseltamivir (Tamiflu).

Nearly all (93%) of the patients were white; 61% had an influenza A strain infection, and there were comparable numbers of male and female study subjects.

Vomiting, fever, and tympanic membrane erythema were the most common adverse effects specifically reported in the study, which was funded by BioCryst.

Peramivir is the third neuraminidase inhibitor (NAI) to be approved; other approved NAIs include oral oseltamivir and inhaled zanamivir.

A fourth NAI, intravenous zanamivir, is still investigational in the United States.

Peramivir, like other antiviral drugs, may interfere with a live attenuated influenza vaccine and should not be used within 2 weeks after or 48 hours before the use of an LAIV.

While the AAP’s recommendations highlight the antiviral’s effectiveness in controlling influenza, the Academy warns that antivirals are not a substitute for influenza vaccination.

[email protected]

It might be prudent to monitor N-terminal pro–B-type natriuretic peptide (NT-proBNP) and skip natriuretic peptide measures in heart failure patients on sacubitril/valsartan (Entresto), according to a new expert consensus document from the American College of Cardiology on managing heart failure with reduced ejection fraction.

“While rising natriuretic peptide concentrations are correlated with adverse outcomes, this relationship can be confounded with the use of sacubitril/valsartan. Due to neprilysin inhibition, concentrations of BNP rise in patients treated with sacubitril/valsartan and tend not to return to baseline despite chronic therapy. In contrast, NT-proBNP concentrations typically decrease, as NT-proBNP is not a substrate for neprilysin,” explained authors led by heart failure pathway writing committee chairman Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago (J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025).

[email protected]

SOURCE: Yancy C et. al. J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025

It might be prudent to monitor N-terminal pro–B-type natriuretic peptide (NT-proBNP) and skip natriuretic peptide measures in heart failure patients on sacubitril/valsartan (Entresto), according to a new expert consensus document from the American College of Cardiology on managing heart failure with reduced ejection fraction.

“While rising natriuretic peptide concentrations are correlated with adverse outcomes, this relationship can be confounded with the use of sacubitril/valsartan. Due to neprilysin inhibition, concentrations of BNP rise in patients treated with sacubitril/valsartan and tend not to return to baseline despite chronic therapy. In contrast, NT-proBNP concentrations typically decrease, as NT-proBNP is not a substrate for neprilysin,” explained authors led by heart failure pathway writing committee chairman Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago (J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025).

[email protected]

SOURCE: Yancy C et. al. J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025

It might be prudent to monitor N-terminal pro–B-type natriuretic peptide (NT-proBNP) and skip natriuretic peptide measures in heart failure patients on sacubitril/valsartan (Entresto), according to a new expert consensus document from the American College of Cardiology on managing heart failure with reduced ejection fraction.

“While rising natriuretic peptide concentrations are correlated with adverse outcomes, this relationship can be confounded with the use of sacubitril/valsartan. Due to neprilysin inhibition, concentrations of BNP rise in patients treated with sacubitril/valsartan and tend not to return to baseline despite chronic therapy. In contrast, NT-proBNP concentrations typically decrease, as NT-proBNP is not a substrate for neprilysin,” explained authors led by heart failure pathway writing committee chairman Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago (J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025).

[email protected]

SOURCE: Yancy C et. al. J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025

MONTREAL – The risk for unplanned cesarean delivery is increased when maternal gestational weight gain exceeds the recommended amount – as it does in almost half of pregnancies in the United States.

In a new analysis of data from the Infant Feeding Practices Study II (IFPS II), women with excessive gestational weight gain (GWG) were found to have an adjusted odds ratio of 1.61 for unplanned cesarean delivery, compared with women with adequate GWG (95% confidence interval, 1.11-2.33; P = .013).

Kari Oakes/Frontline Medical News

[email protected]

SOURCE: Francescon J. NAPCRG 2017 Abstract P495.

MONTREAL – The risk for unplanned cesarean delivery is increased when maternal gestational weight gain exceeds the recommended amount – as it does in almost half of pregnancies in the United States.

In a new analysis of data from the Infant Feeding Practices Study II (IFPS II), women with excessive gestational weight gain (GWG) were found to have an adjusted odds ratio of 1.61 for unplanned cesarean delivery, compared with women with adequate GWG (95% confidence interval, 1.11-2.33; P = .013).

Kari Oakes/Frontline Medical News

[email protected]

SOURCE: Francescon J. NAPCRG 2017 Abstract P495.

MONTREAL – The risk for unplanned cesarean delivery is increased when maternal gestational weight gain exceeds the recommended amount – as it does in almost half of pregnancies in the United States.

In a new analysis of data from the Infant Feeding Practices Study II (IFPS II), women with excessive gestational weight gain (GWG) were found to have an adjusted odds ratio of 1.61 for unplanned cesarean delivery, compared with women with adequate GWG (95% confidence interval, 1.11-2.33; P = .013).

Kari Oakes/Frontline Medical News

[email protected]

SOURCE: Francescon J. NAPCRG 2017 Abstract P495.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.