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VIDEO: Venetoclax/rituximab prolongs PFS in relapsed/refractory CLL
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
REPORTING FROM ASH 2017
PCVs reduced CAP hospitalizations in young children but not other age groups
, but there was no clear impact apparent in other age groups, reported Annemarie van Deursen, MD, of the University Medical Centre (the Netherlands) Utrecht, and her associates.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the national infant immunization program in 2006; in 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). The investigators undertook a population-based retrospective study during 1999-2014 on all-cause CAP hospitalizations in all ages, identifying 155,994 CAP hospitalizations.
In children aged 0-6 months, the CAP hospitalization rate ratio (RR) was significant from 2012 onward, with an overall post-PCV RR of 0.62 and a RR of 0.19 at the end of the study period in December 2014. In children aged 6 months-1 year, the RR was statistically significant directly after the introduction of PCV, with an overall post-PCV RR of 0.67 and a RR of 0.47 in December 2014, the investigators wrote.
In none of the other age groups did the overall post-PCV hospitalization RR reach statistical significance.
The association of reductions in CAP hospitalizations in children up to 2 years with the introduction of PCV7 “supports the interpretation for a direct causal effect of PCV7, in line with IPD [invasive pneumococcal disease] results that showed a sustained overall IPD reduction in children,” the investigators said. “Furthermore, [during] each subsequent year of the post-PCV period, the reduction in CAP hospitalization rates increased in line with progressive vaccine-type–IPD reduction in the population and limited replacement by nonvaccine type in childhood IPD.”
Read more in Vaccine (2017 Nov 13. doi: 10.1016/j.vaccine.2017.10.090).
, but there was no clear impact apparent in other age groups, reported Annemarie van Deursen, MD, of the University Medical Centre (the Netherlands) Utrecht, and her associates.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the national infant immunization program in 2006; in 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). The investigators undertook a population-based retrospective study during 1999-2014 on all-cause CAP hospitalizations in all ages, identifying 155,994 CAP hospitalizations.
In children aged 0-6 months, the CAP hospitalization rate ratio (RR) was significant from 2012 onward, with an overall post-PCV RR of 0.62 and a RR of 0.19 at the end of the study period in December 2014. In children aged 6 months-1 year, the RR was statistically significant directly after the introduction of PCV, with an overall post-PCV RR of 0.67 and a RR of 0.47 in December 2014, the investigators wrote.
In none of the other age groups did the overall post-PCV hospitalization RR reach statistical significance.
The association of reductions in CAP hospitalizations in children up to 2 years with the introduction of PCV7 “supports the interpretation for a direct causal effect of PCV7, in line with IPD [invasive pneumococcal disease] results that showed a sustained overall IPD reduction in children,” the investigators said. “Furthermore, [during] each subsequent year of the post-PCV period, the reduction in CAP hospitalization rates increased in line with progressive vaccine-type–IPD reduction in the population and limited replacement by nonvaccine type in childhood IPD.”
Read more in Vaccine (2017 Nov 13. doi: 10.1016/j.vaccine.2017.10.090).
, but there was no clear impact apparent in other age groups, reported Annemarie van Deursen, MD, of the University Medical Centre (the Netherlands) Utrecht, and her associates.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the national infant immunization program in 2006; in 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). The investigators undertook a population-based retrospective study during 1999-2014 on all-cause CAP hospitalizations in all ages, identifying 155,994 CAP hospitalizations.
In children aged 0-6 months, the CAP hospitalization rate ratio (RR) was significant from 2012 onward, with an overall post-PCV RR of 0.62 and a RR of 0.19 at the end of the study period in December 2014. In children aged 6 months-1 year, the RR was statistically significant directly after the introduction of PCV, with an overall post-PCV RR of 0.67 and a RR of 0.47 in December 2014, the investigators wrote.
In none of the other age groups did the overall post-PCV hospitalization RR reach statistical significance.
The association of reductions in CAP hospitalizations in children up to 2 years with the introduction of PCV7 “supports the interpretation for a direct causal effect of PCV7, in line with IPD [invasive pneumococcal disease] results that showed a sustained overall IPD reduction in children,” the investigators said. “Furthermore, [during] each subsequent year of the post-PCV period, the reduction in CAP hospitalization rates increased in line with progressive vaccine-type–IPD reduction in the population and limited replacement by nonvaccine type in childhood IPD.”
Read more in Vaccine (2017 Nov 13. doi: 10.1016/j.vaccine.2017.10.090).
FROM VACCINE
Antibiotics Before Dental Surgery—or Not?
Does antibiotic prophylaxis protect patients with cardiac conditions against endocarditis from invasive dental procedures? Studies have long suggested both “yes” and “no.” Researchers from Université Paris Diderot and others note that clinical trials and cohort studies have not proved efficacy. Only 2 case-control studies done in the past 30 years have established an association between dental procedures and streptococcal infective endocarditis; neither was sufficiently powered to establish the efficacy of antibiotic prophylaxis.
Current U.S. and European guidelines vary in who must be covered: all patients, certain patients, or no patients at all. But a rise in the incidence of infective endocarditis among patients with prosthetic heart valves, implicating invasive dental procedures, “raised the question of whether the indications for antibiotic prophylaxis may be broadened again,” the researchers say. They cite 2016 NICE guidelines that “clearly specify” that it may be appropriate in individual cases.
Given that endocarditis can be fatal or expensive to treat—hospitals stays are long and valve surgery may be needed—the researchers decided to evaluate the association between invasive dental procedures and oral streptococcal infective endocarditis in a population-based cohort and a case crossover study.
In the first study of 138,876 patients with prosthetic heart valves, 69,303 underwent at least 1 dental procedure. Of 396,615 dental procedures, 26% were invasive. Patients received prophylactic antibiotics before half of the procedures.
Over a median 1.7 years of follow-up, 267 people developed infective endocarditis associated with oral streptococci. However, the rate of oral streptococcal infective endocarditis did not rise significantly in the 3 months after an invasive dental procedure, with or without antibiotic prophylaxis.
The case crossover study of patients with endocarditis indicated “the same direction of effect”: Although invasive dental procedures may be associated with oral streptococcal infective endocarditis, the magnitude of the association “remains uncertain.”
Source:
Tubiana S, Blotière PO, Hoen B, et al. BMJ. 2017;358: j3776.
doi: 10.1136/bmj.j3776.
Does antibiotic prophylaxis protect patients with cardiac conditions against endocarditis from invasive dental procedures? Studies have long suggested both “yes” and “no.” Researchers from Université Paris Diderot and others note that clinical trials and cohort studies have not proved efficacy. Only 2 case-control studies done in the past 30 years have established an association between dental procedures and streptococcal infective endocarditis; neither was sufficiently powered to establish the efficacy of antibiotic prophylaxis.
Current U.S. and European guidelines vary in who must be covered: all patients, certain patients, or no patients at all. But a rise in the incidence of infective endocarditis among patients with prosthetic heart valves, implicating invasive dental procedures, “raised the question of whether the indications for antibiotic prophylaxis may be broadened again,” the researchers say. They cite 2016 NICE guidelines that “clearly specify” that it may be appropriate in individual cases.
Given that endocarditis can be fatal or expensive to treat—hospitals stays are long and valve surgery may be needed—the researchers decided to evaluate the association between invasive dental procedures and oral streptococcal infective endocarditis in a population-based cohort and a case crossover study.
In the first study of 138,876 patients with prosthetic heart valves, 69,303 underwent at least 1 dental procedure. Of 396,615 dental procedures, 26% were invasive. Patients received prophylactic antibiotics before half of the procedures.
Over a median 1.7 years of follow-up, 267 people developed infective endocarditis associated with oral streptococci. However, the rate of oral streptococcal infective endocarditis did not rise significantly in the 3 months after an invasive dental procedure, with or without antibiotic prophylaxis.
The case crossover study of patients with endocarditis indicated “the same direction of effect”: Although invasive dental procedures may be associated with oral streptococcal infective endocarditis, the magnitude of the association “remains uncertain.”
Source:
Tubiana S, Blotière PO, Hoen B, et al. BMJ. 2017;358: j3776.
doi: 10.1136/bmj.j3776.
Does antibiotic prophylaxis protect patients with cardiac conditions against endocarditis from invasive dental procedures? Studies have long suggested both “yes” and “no.” Researchers from Université Paris Diderot and others note that clinical trials and cohort studies have not proved efficacy. Only 2 case-control studies done in the past 30 years have established an association between dental procedures and streptococcal infective endocarditis; neither was sufficiently powered to establish the efficacy of antibiotic prophylaxis.
Current U.S. and European guidelines vary in who must be covered: all patients, certain patients, or no patients at all. But a rise in the incidence of infective endocarditis among patients with prosthetic heart valves, implicating invasive dental procedures, “raised the question of whether the indications for antibiotic prophylaxis may be broadened again,” the researchers say. They cite 2016 NICE guidelines that “clearly specify” that it may be appropriate in individual cases.
Given that endocarditis can be fatal or expensive to treat—hospitals stays are long and valve surgery may be needed—the researchers decided to evaluate the association between invasive dental procedures and oral streptococcal infective endocarditis in a population-based cohort and a case crossover study.
In the first study of 138,876 patients with prosthetic heart valves, 69,303 underwent at least 1 dental procedure. Of 396,615 dental procedures, 26% were invasive. Patients received prophylactic antibiotics before half of the procedures.
Over a median 1.7 years of follow-up, 267 people developed infective endocarditis associated with oral streptococci. However, the rate of oral streptococcal infective endocarditis did not rise significantly in the 3 months after an invasive dental procedure, with or without antibiotic prophylaxis.
The case crossover study of patients with endocarditis indicated “the same direction of effect”: Although invasive dental procedures may be associated with oral streptococcal infective endocarditis, the magnitude of the association “remains uncertain.”
Source:
Tubiana S, Blotière PO, Hoen B, et al. BMJ. 2017;358: j3776.
doi: 10.1136/bmj.j3776.
Flu vaccine did not protect children with acute leukemia
said April Sykes of St. Jude Children’s Research Hospital in Carmel, Ind., and her associates.
Patients aged 1-21 years being treated for acute leukemia during three successive influenza seasons (2011-2012, 2012-2013, and 2013-2014) were identified by a retrospective review of EHRs; of those patients, 354 (71%) patients received TIV, and 98 (20%) received a booster dose of flu vaccine.
Also, whether the children and youth received one or two doses of flu vaccine made no difference in the rates of influenza (0.60 vs. 1.02; P = .107), the investigators reported.
These data suggest “that influenza vaccine may be ineffective in children receiving therapy for acute leukemia and that routine administration of TIV may not reflect high-value care,” the researchers said. “Until more immunogenic and protective vaccines are developed, efforts to prevent influenza in high-risk populations should focus on more general strategies, such as avoiding ill persons and practicing good respiratory hygiene in households and health care facilities.”
Read more in the Journal of Pediatrics (2017 Nov 21. doi: 10.1016/j.jpeds.2017.08.071).
said April Sykes of St. Jude Children’s Research Hospital in Carmel, Ind., and her associates.
Patients aged 1-21 years being treated for acute leukemia during three successive influenza seasons (2011-2012, 2012-2013, and 2013-2014) were identified by a retrospective review of EHRs; of those patients, 354 (71%) patients received TIV, and 98 (20%) received a booster dose of flu vaccine.
Also, whether the children and youth received one or two doses of flu vaccine made no difference in the rates of influenza (0.60 vs. 1.02; P = .107), the investigators reported.
These data suggest “that influenza vaccine may be ineffective in children receiving therapy for acute leukemia and that routine administration of TIV may not reflect high-value care,” the researchers said. “Until more immunogenic and protective vaccines are developed, efforts to prevent influenza in high-risk populations should focus on more general strategies, such as avoiding ill persons and practicing good respiratory hygiene in households and health care facilities.”
Read more in the Journal of Pediatrics (2017 Nov 21. doi: 10.1016/j.jpeds.2017.08.071).
said April Sykes of St. Jude Children’s Research Hospital in Carmel, Ind., and her associates.
Patients aged 1-21 years being treated for acute leukemia during three successive influenza seasons (2011-2012, 2012-2013, and 2013-2014) were identified by a retrospective review of EHRs; of those patients, 354 (71%) patients received TIV, and 98 (20%) received a booster dose of flu vaccine.
Also, whether the children and youth received one or two doses of flu vaccine made no difference in the rates of influenza (0.60 vs. 1.02; P = .107), the investigators reported.
These data suggest “that influenza vaccine may be ineffective in children receiving therapy for acute leukemia and that routine administration of TIV may not reflect high-value care,” the researchers said. “Until more immunogenic and protective vaccines are developed, efforts to prevent influenza in high-risk populations should focus on more general strategies, such as avoiding ill persons and practicing good respiratory hygiene in households and health care facilities.”
Read more in the Journal of Pediatrics (2017 Nov 21. doi: 10.1016/j.jpeds.2017.08.071).
FROM THE JOURNAL OF PEDIATRICS
VIDEO: CAR T cell axi-cel drives B-cell lymphomas into remission
ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.
Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.
In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.
ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.
Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.
In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.
ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ATLANTA – In the ZUMA-1 trial, more than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta; axi-cel) had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion.
Updated combined phase 1 and 2 results in 108 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma showed an objective response rate of 82% of patients – including 58% showing complete responses – after a median follow-up of 15.4 months.
In a video interview at the annual meeting of the American Society of Hematology, Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston discusses the use of CAR T cells directed against the CD19 antigen in patients with relapsed/refractory B-cell lymphomas and describes efforts to improve responses while managing adverse events common to CAR T-cell therapies, notably cytokine release syndrome.
ZUMA-1 is supported by Kite Pharma, which developed axicabtagene ciloleucel, and the Leukemia & Lymphoma Society’s Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM ASH 2017
Three-month response to CAR T-cells looks durable in DLBCL
ATLANTA – Responses 3 months after chimeric antigen receptor (CAR) T-cell therapy look durable in adults with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated results from the single-arm, global, phase 2 JULIET trial.
Fully 95% of patients who had a complete response to CTL019 (tisagenlecleucel; Kymriah) at 3 months maintained that complete response at 6 months, Stephen J. Schuster, MD, said at the annual meeting of the American Society of Hematology.
Patients with relapsed/refractory DLBCL tend to face a very poor prognosis, noted Dr. Schuster of Perelman School of Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia. High-dose chemotherapy followed by autologous stem cell transplantation “is capable of long-term survival, but in very few patients,” he said. A dismal 8% of patients completely respond to salvage treatment and only about one in five partially respond. Both levels of response are short-lived, with a median survival of about 4 months.
Meanwhile, CTL019 therapy has produced durable complete remissions in children with lymphoblastic leukemia and in adults with chronic lymphocytic leukemia, Dr. Schuster and his associates wrote in an article simultaneously published in the New England Journal of Medicine (2017 Dec 10. doi: 10.1056/NEJMoa1708566).
To test the CAR T-cell therapy in relapsed/refractory DLBCL, they enrolled affected adults who had received at least two prior lines of antineoplastic treatment and who were not candidates for autologous stem cell transplantation.
Treatment consisted of a single CTL019 infusion (median dose, 3.1 × 108 cells; range, 0.1 × 108 to 6.0 × 108 cells), usually after lymphodepleting chemotherapy. Previously, patients had received a median of three lines of therapy, and about half had undergone autologous stem cell transplantation.
Median time from infusion to data cutoff in March 2017 was 5.6 months. Among 81 patients followed for at least 3 months before data cutoff, best overall response rate was 53% and 40% had a complete response. Overall response rates were 38% at 3 months and 37% at 6 months. Rates of complete response as confirmed by 18F-fluorodeoxyglucose–positron-emission tomography (PET) were 32% at 3 months and 30% at 6 months.These findings highlight the predictive power of 3-month response to CTL019 therapy in relapsed/refractory DLBCL, Dr. Schuster said. Among all responders, 74% remained relapse free at 6 months, meaning that median duration of response and median overall survival were not reached at data cutoff.
Dr. Schuster also reported that 26% of patients were infused as outpatients, which he called “easy to do” and appropriate as long as patients who become febrile are admitted and monitored for cytokine release syndrome. Three-quarters of patients who were infused as outpatients were able to remain home for at least 3 days afterward, he said.
Adverse events typified those of CAR T-cell therapy, including cytokine release syndrome (all grades: 58%; grade 3-4: 23%) and neurological toxicities (all grades: 21%; grade 3-4: 12%). The current labeling for CTL019 in children and young adults with acute lymphoblastic leukemia also includes a boxed warning for these toxicities.Tisagenlecleucel, the first-ever approved CAR T-cell therapy, is made by using a lentiviral vector to genetically engineer a patient’s own T-cells to express a CAR for the pan-B-cell CD19 antigen. These anti-CD19 CAR T-cells are then expanded in the laboratory, frozen for shipping purposes, and infused back into patients. In October 2017, Novartis submitted a biologics license application to the Food and Drug Administration to expand the label for CTL019 to include transplant-ineligible relapsed/refractory DLBCL.
Novartis Pharmaceuticals anticipates large-scale production in 2018, Dr. Schuster said. Manufacturing time has been cut to 22 days from the 30-day turnaround used in the trial, he reported.
Dr. Schuster also said that he sees no point in retreating patients whose relapsed/refractory DLBCL doesn’t respond to tisagenlecleucel, and that JULIET did not test this approach. “If someone fails therapy and you retreat, you don’t see success, in my experience,” he said. “If patients respond and then fail later, then you retreat and you may succeed.”
Novartis Pharmaceuticals sponsored JULIET. Dr. Schuster disclosed consultancy and research funding from Novartis and ties to Celgene, Gilead, Genentech, and several other pharmaceutical companies.
SOURCE: Schuster S et al. ASH 2017 Abstract 577.
ATLANTA – Responses 3 months after chimeric antigen receptor (CAR) T-cell therapy look durable in adults with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated results from the single-arm, global, phase 2 JULIET trial.
Fully 95% of patients who had a complete response to CTL019 (tisagenlecleucel; Kymriah) at 3 months maintained that complete response at 6 months, Stephen J. Schuster, MD, said at the annual meeting of the American Society of Hematology.
Patients with relapsed/refractory DLBCL tend to face a very poor prognosis, noted Dr. Schuster of Perelman School of Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia. High-dose chemotherapy followed by autologous stem cell transplantation “is capable of long-term survival, but in very few patients,” he said. A dismal 8% of patients completely respond to salvage treatment and only about one in five partially respond. Both levels of response are short-lived, with a median survival of about 4 months.
Meanwhile, CTL019 therapy has produced durable complete remissions in children with lymphoblastic leukemia and in adults with chronic lymphocytic leukemia, Dr. Schuster and his associates wrote in an article simultaneously published in the New England Journal of Medicine (2017 Dec 10. doi: 10.1056/NEJMoa1708566).
To test the CAR T-cell therapy in relapsed/refractory DLBCL, they enrolled affected adults who had received at least two prior lines of antineoplastic treatment and who were not candidates for autologous stem cell transplantation.
Treatment consisted of a single CTL019 infusion (median dose, 3.1 × 108 cells; range, 0.1 × 108 to 6.0 × 108 cells), usually after lymphodepleting chemotherapy. Previously, patients had received a median of three lines of therapy, and about half had undergone autologous stem cell transplantation.
Median time from infusion to data cutoff in March 2017 was 5.6 months. Among 81 patients followed for at least 3 months before data cutoff, best overall response rate was 53% and 40% had a complete response. Overall response rates were 38% at 3 months and 37% at 6 months. Rates of complete response as confirmed by 18F-fluorodeoxyglucose–positron-emission tomography (PET) were 32% at 3 months and 30% at 6 months.These findings highlight the predictive power of 3-month response to CTL019 therapy in relapsed/refractory DLBCL, Dr. Schuster said. Among all responders, 74% remained relapse free at 6 months, meaning that median duration of response and median overall survival were not reached at data cutoff.
Dr. Schuster also reported that 26% of patients were infused as outpatients, which he called “easy to do” and appropriate as long as patients who become febrile are admitted and monitored for cytokine release syndrome. Three-quarters of patients who were infused as outpatients were able to remain home for at least 3 days afterward, he said.
Adverse events typified those of CAR T-cell therapy, including cytokine release syndrome (all grades: 58%; grade 3-4: 23%) and neurological toxicities (all grades: 21%; grade 3-4: 12%). The current labeling for CTL019 in children and young adults with acute lymphoblastic leukemia also includes a boxed warning for these toxicities.Tisagenlecleucel, the first-ever approved CAR T-cell therapy, is made by using a lentiviral vector to genetically engineer a patient’s own T-cells to express a CAR for the pan-B-cell CD19 antigen. These anti-CD19 CAR T-cells are then expanded in the laboratory, frozen for shipping purposes, and infused back into patients. In October 2017, Novartis submitted a biologics license application to the Food and Drug Administration to expand the label for CTL019 to include transplant-ineligible relapsed/refractory DLBCL.
Novartis Pharmaceuticals anticipates large-scale production in 2018, Dr. Schuster said. Manufacturing time has been cut to 22 days from the 30-day turnaround used in the trial, he reported.
Dr. Schuster also said that he sees no point in retreating patients whose relapsed/refractory DLBCL doesn’t respond to tisagenlecleucel, and that JULIET did not test this approach. “If someone fails therapy and you retreat, you don’t see success, in my experience,” he said. “If patients respond and then fail later, then you retreat and you may succeed.”
Novartis Pharmaceuticals sponsored JULIET. Dr. Schuster disclosed consultancy and research funding from Novartis and ties to Celgene, Gilead, Genentech, and several other pharmaceutical companies.
SOURCE: Schuster S et al. ASH 2017 Abstract 577.
ATLANTA – Responses 3 months after chimeric antigen receptor (CAR) T-cell therapy look durable in adults with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated results from the single-arm, global, phase 2 JULIET trial.
Fully 95% of patients who had a complete response to CTL019 (tisagenlecleucel; Kymriah) at 3 months maintained that complete response at 6 months, Stephen J. Schuster, MD, said at the annual meeting of the American Society of Hematology.
Patients with relapsed/refractory DLBCL tend to face a very poor prognosis, noted Dr. Schuster of Perelman School of Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia. High-dose chemotherapy followed by autologous stem cell transplantation “is capable of long-term survival, but in very few patients,” he said. A dismal 8% of patients completely respond to salvage treatment and only about one in five partially respond. Both levels of response are short-lived, with a median survival of about 4 months.
Meanwhile, CTL019 therapy has produced durable complete remissions in children with lymphoblastic leukemia and in adults with chronic lymphocytic leukemia, Dr. Schuster and his associates wrote in an article simultaneously published in the New England Journal of Medicine (2017 Dec 10. doi: 10.1056/NEJMoa1708566).
To test the CAR T-cell therapy in relapsed/refractory DLBCL, they enrolled affected adults who had received at least two prior lines of antineoplastic treatment and who were not candidates for autologous stem cell transplantation.
Treatment consisted of a single CTL019 infusion (median dose, 3.1 × 108 cells; range, 0.1 × 108 to 6.0 × 108 cells), usually after lymphodepleting chemotherapy. Previously, patients had received a median of three lines of therapy, and about half had undergone autologous stem cell transplantation.
Median time from infusion to data cutoff in March 2017 was 5.6 months. Among 81 patients followed for at least 3 months before data cutoff, best overall response rate was 53% and 40% had a complete response. Overall response rates were 38% at 3 months and 37% at 6 months. Rates of complete response as confirmed by 18F-fluorodeoxyglucose–positron-emission tomography (PET) were 32% at 3 months and 30% at 6 months.These findings highlight the predictive power of 3-month response to CTL019 therapy in relapsed/refractory DLBCL, Dr. Schuster said. Among all responders, 74% remained relapse free at 6 months, meaning that median duration of response and median overall survival were not reached at data cutoff.
Dr. Schuster also reported that 26% of patients were infused as outpatients, which he called “easy to do” and appropriate as long as patients who become febrile are admitted and monitored for cytokine release syndrome. Three-quarters of patients who were infused as outpatients were able to remain home for at least 3 days afterward, he said.
Adverse events typified those of CAR T-cell therapy, including cytokine release syndrome (all grades: 58%; grade 3-4: 23%) and neurological toxicities (all grades: 21%; grade 3-4: 12%). The current labeling for CTL019 in children and young adults with acute lymphoblastic leukemia also includes a boxed warning for these toxicities.Tisagenlecleucel, the first-ever approved CAR T-cell therapy, is made by using a lentiviral vector to genetically engineer a patient’s own T-cells to express a CAR for the pan-B-cell CD19 antigen. These anti-CD19 CAR T-cells are then expanded in the laboratory, frozen for shipping purposes, and infused back into patients. In October 2017, Novartis submitted a biologics license application to the Food and Drug Administration to expand the label for CTL019 to include transplant-ineligible relapsed/refractory DLBCL.
Novartis Pharmaceuticals anticipates large-scale production in 2018, Dr. Schuster said. Manufacturing time has been cut to 22 days from the 30-day turnaround used in the trial, he reported.
Dr. Schuster also said that he sees no point in retreating patients whose relapsed/refractory DLBCL doesn’t respond to tisagenlecleucel, and that JULIET did not test this approach. “If someone fails therapy and you retreat, you don’t see success, in my experience,” he said. “If patients respond and then fail later, then you retreat and you may succeed.”
Novartis Pharmaceuticals sponsored JULIET. Dr. Schuster disclosed consultancy and research funding from Novartis and ties to Celgene, Gilead, Genentech, and several other pharmaceutical companies.
SOURCE: Schuster S et al. ASH 2017 Abstract 577.
REPORTING FROM ASH 2017
Key clinical point:
Major finding: Among 81 patients with at least 3 months of follow-up, best overall response rate was 53% (95% CI, 42%-64%; P less than .0001) and rates of complete response were 32% at 3 months and 30% at 6 months.
Study details: JULIET is an international, single-arm, phase 2 study of adults with relapsed/refractory DLBCL.
Disclosures: Novartis Pharmaceuticals sponsored JULIET. Dr. Schuster reported consultancy and research funding from Novartis and ties to Celgene, Gilead, Genentech, and several other pharmaceutical companies.
Source: Schuster S et al. ASH 2017 Abstract 577.
A Medication Tracker That Patients Swallow
Making sure some patients are taking their medication correctly may be a little easier now. The FDA has approved Abilify MyCite (apiprazole), which has an ingestible sensor.
Abilify MyCite is approved for treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar 1 disorder, and as an add-on treatment for depression in adults.
The sensor, embedded in the pill, records when the medicine was taken, and sends a message to a wearable patch, which then transmits information to a mobile application. Patients can track the ingestion of the medication on their smartphone and can allow their caregivers and physicians to access information through a web-based portal.
However, the FDA notes that Abilify MyCite’s prescribing information includes a caution that the product has not been shown to improve patient adherence with a treatment regimen. Moreover, Ability MyCite should not be used to track drug ingestion in real time or during an emergency, because detection may be delayed or may not occur. Before prescribing it for a patient, health care professionals should make sure the patient is capable and willing to use the drug, patch, and app.
Making sure some patients are taking their medication correctly may be a little easier now. The FDA has approved Abilify MyCite (apiprazole), which has an ingestible sensor.
Abilify MyCite is approved for treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar 1 disorder, and as an add-on treatment for depression in adults.
The sensor, embedded in the pill, records when the medicine was taken, and sends a message to a wearable patch, which then transmits information to a mobile application. Patients can track the ingestion of the medication on their smartphone and can allow their caregivers and physicians to access information through a web-based portal.
However, the FDA notes that Abilify MyCite’s prescribing information includes a caution that the product has not been shown to improve patient adherence with a treatment regimen. Moreover, Ability MyCite should not be used to track drug ingestion in real time or during an emergency, because detection may be delayed or may not occur. Before prescribing it for a patient, health care professionals should make sure the patient is capable and willing to use the drug, patch, and app.
Making sure some patients are taking their medication correctly may be a little easier now. The FDA has approved Abilify MyCite (apiprazole), which has an ingestible sensor.
Abilify MyCite is approved for treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar 1 disorder, and as an add-on treatment for depression in adults.
The sensor, embedded in the pill, records when the medicine was taken, and sends a message to a wearable patch, which then transmits information to a mobile application. Patients can track the ingestion of the medication on their smartphone and can allow their caregivers and physicians to access information through a web-based portal.
However, the FDA notes that Abilify MyCite’s prescribing information includes a caution that the product has not been shown to improve patient adherence with a treatment regimen. Moreover, Ability MyCite should not be used to track drug ingestion in real time or during an emergency, because detection may be delayed or may not occur. Before prescribing it for a patient, health care professionals should make sure the patient is capable and willing to use the drug, patch, and app.
MAVORIC: Mogamulizumab tops vorinostat in pretreated CTCL
ATLANTA – Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
After a median of three treatment cycles, median PFS with mogamulizumab was 7.7 months vs. 3.1 months with vorinostat (hazard ratio, 0.53; 95% confidence interval, 0.41-0.69; P less than .0001), Youn H. Kim, MD, reported at the annual meeting of the American Society of Hematology.
, said Dr. Kim, the Joanne and Peter Haas, Jr. Professor for Cutaneous Lymphoma Research at Stanford (Calif.) University. Adverse effects, such as infusion reactions, were expected and manageable, she added.
Mogamulizumab is approved in Japan for treating CTCL and received an FDA breakthrough therapy designation in August 2017.
Based on audits so far, the agency might green-light mogamulizumab for previously treated CTCL by early 2018 – its first approval in the United States, Dr. Kim said in an interview.
Cutaneous T-cell lymphoma responds poorly to treatments that work in other, more common types of non-Hodgkin lymphoma. Moreover, extensive disease can destroy quality of life.
“There’s a major psychosocial impact because if you’re infected, you smell bad,” Dr. Kim said during a press briefing. “Itch is very severe – patients often cannot sleep because of it.”
Mogamulizumab is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), which facilitates trafficking of lymphocytes to skin and other organs. It is defucosylated, augmenting its toxicity against malignant T cells. In a prior phase 1/2 study in the United States, mogamulizumab showed a tolerable safety profile and a 37% overall response rate – “a good response, considering that other CTCL drugs are usually in the 30% range,” Dr. Kim said.
For the phase 3 study (MAVORIC), 372 patients with previously treated stage IB to stage IVB CTCL (mycosis fungoides or Sézary syndrome) without large-cell transformation received mogamulizumab (1.0 mg/kg IV weekly for 28 days; days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg per oral daily). Treatment continued until disease progression or intolerable toxicity. Researchers evaluated PFS based on a global composite response score that covers the skin, blood, lymph nodes, and viscera, in accordance with international consensus guidelines (J Clin Oncol. 2011 Jun 20;29(18):2598-607; doi: 10.1200/JCO.2010.32.0630).
Treatment groups resembled each other at baseline. Most had received three systemic therapies for CTCL, and some had received as many as 18. Median duration of response was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. Patients tended to respond to mogamulizumab 2 months sooner than to vorinostat (3.3 vs. 5.1 months), Dr. Kim said.
Mogamulizumab also significantly improved quality of life on the Skindex-29 Symptoms (P less than .05), Skindex-29 Function (P less than 05), and FACT-G Functional Well-Being (P less than .05) quality of life scales, which is part of what earned it a breakthrough therapy designation, Dr. Kim said.
MAVORIC is the largest randomized study to compare systemic therapies in CTCL and the first to use PFS as the primary endpoint, Dr. Kim noted. Patients’ level of CCR4 expression was not a criterion for enrollment because CCR4 is consistently and highly expressed in this disease, she noted. Thus, using mogamulizumab to treat CTCL in the United States would not require CCR4 testing.
Joseph M. Connors, MD, who specializes in lymphoid cancers at the BC Cancer Agency, a division of the British Columbia Provincial Health Services Authority, and who was not involved in the study, agreed that these data represent real headway in treating CTCL.
“I can state unequivocally that we just haven’t had effective therapy for CTCL,” he said at the press briefing. “We’ve had treatments that might help patients feel somewhat better, but we’ve had no consensus on a treatment that is right for this disease. These data provide an opportunity to have that consensus. They could create a platform for making further progress.”
Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
SOURCE: Kim YH et al. ASH 2017 Abstract 817.
ATLANTA – Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
After a median of three treatment cycles, median PFS with mogamulizumab was 7.7 months vs. 3.1 months with vorinostat (hazard ratio, 0.53; 95% confidence interval, 0.41-0.69; P less than .0001), Youn H. Kim, MD, reported at the annual meeting of the American Society of Hematology.
, said Dr. Kim, the Joanne and Peter Haas, Jr. Professor for Cutaneous Lymphoma Research at Stanford (Calif.) University. Adverse effects, such as infusion reactions, were expected and manageable, she added.
Mogamulizumab is approved in Japan for treating CTCL and received an FDA breakthrough therapy designation in August 2017.
Based on audits so far, the agency might green-light mogamulizumab for previously treated CTCL by early 2018 – its first approval in the United States, Dr. Kim said in an interview.
Cutaneous T-cell lymphoma responds poorly to treatments that work in other, more common types of non-Hodgkin lymphoma. Moreover, extensive disease can destroy quality of life.
“There’s a major psychosocial impact because if you’re infected, you smell bad,” Dr. Kim said during a press briefing. “Itch is very severe – patients often cannot sleep because of it.”
Mogamulizumab is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), which facilitates trafficking of lymphocytes to skin and other organs. It is defucosylated, augmenting its toxicity against malignant T cells. In a prior phase 1/2 study in the United States, mogamulizumab showed a tolerable safety profile and a 37% overall response rate – “a good response, considering that other CTCL drugs are usually in the 30% range,” Dr. Kim said.
For the phase 3 study (MAVORIC), 372 patients with previously treated stage IB to stage IVB CTCL (mycosis fungoides or Sézary syndrome) without large-cell transformation received mogamulizumab (1.0 mg/kg IV weekly for 28 days; days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg per oral daily). Treatment continued until disease progression or intolerable toxicity. Researchers evaluated PFS based on a global composite response score that covers the skin, blood, lymph nodes, and viscera, in accordance with international consensus guidelines (J Clin Oncol. 2011 Jun 20;29(18):2598-607; doi: 10.1200/JCO.2010.32.0630).
Treatment groups resembled each other at baseline. Most had received three systemic therapies for CTCL, and some had received as many as 18. Median duration of response was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. Patients tended to respond to mogamulizumab 2 months sooner than to vorinostat (3.3 vs. 5.1 months), Dr. Kim said.
Mogamulizumab also significantly improved quality of life on the Skindex-29 Symptoms (P less than .05), Skindex-29 Function (P less than 05), and FACT-G Functional Well-Being (P less than .05) quality of life scales, which is part of what earned it a breakthrough therapy designation, Dr. Kim said.
MAVORIC is the largest randomized study to compare systemic therapies in CTCL and the first to use PFS as the primary endpoint, Dr. Kim noted. Patients’ level of CCR4 expression was not a criterion for enrollment because CCR4 is consistently and highly expressed in this disease, she noted. Thus, using mogamulizumab to treat CTCL in the United States would not require CCR4 testing.
Joseph M. Connors, MD, who specializes in lymphoid cancers at the BC Cancer Agency, a division of the British Columbia Provincial Health Services Authority, and who was not involved in the study, agreed that these data represent real headway in treating CTCL.
“I can state unequivocally that we just haven’t had effective therapy for CTCL,” he said at the press briefing. “We’ve had treatments that might help patients feel somewhat better, but we’ve had no consensus on a treatment that is right for this disease. These data provide an opportunity to have that consensus. They could create a platform for making further progress.”
Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
SOURCE: Kim YH et al. ASH 2017 Abstract 817.
ATLANTA – Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
After a median of three treatment cycles, median PFS with mogamulizumab was 7.7 months vs. 3.1 months with vorinostat (hazard ratio, 0.53; 95% confidence interval, 0.41-0.69; P less than .0001), Youn H. Kim, MD, reported at the annual meeting of the American Society of Hematology.
, said Dr. Kim, the Joanne and Peter Haas, Jr. Professor for Cutaneous Lymphoma Research at Stanford (Calif.) University. Adverse effects, such as infusion reactions, were expected and manageable, she added.
Mogamulizumab is approved in Japan for treating CTCL and received an FDA breakthrough therapy designation in August 2017.
Based on audits so far, the agency might green-light mogamulizumab for previously treated CTCL by early 2018 – its first approval in the United States, Dr. Kim said in an interview.
Cutaneous T-cell lymphoma responds poorly to treatments that work in other, more common types of non-Hodgkin lymphoma. Moreover, extensive disease can destroy quality of life.
“There’s a major psychosocial impact because if you’re infected, you smell bad,” Dr. Kim said during a press briefing. “Itch is very severe – patients often cannot sleep because of it.”
Mogamulizumab is a humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4), which facilitates trafficking of lymphocytes to skin and other organs. It is defucosylated, augmenting its toxicity against malignant T cells. In a prior phase 1/2 study in the United States, mogamulizumab showed a tolerable safety profile and a 37% overall response rate – “a good response, considering that other CTCL drugs are usually in the 30% range,” Dr. Kim said.
For the phase 3 study (MAVORIC), 372 patients with previously treated stage IB to stage IVB CTCL (mycosis fungoides or Sézary syndrome) without large-cell transformation received mogamulizumab (1.0 mg/kg IV weekly for 28 days; days 1 and 15 of subsequent 28-day cycles) or vorinostat (400 mg per oral daily). Treatment continued until disease progression or intolerable toxicity. Researchers evaluated PFS based on a global composite response score that covers the skin, blood, lymph nodes, and viscera, in accordance with international consensus guidelines (J Clin Oncol. 2011 Jun 20;29(18):2598-607; doi: 10.1200/JCO.2010.32.0630).
Treatment groups resembled each other at baseline. Most had received three systemic therapies for CTCL, and some had received as many as 18. Median duration of response was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm. Patients tended to respond to mogamulizumab 2 months sooner than to vorinostat (3.3 vs. 5.1 months), Dr. Kim said.
Mogamulizumab also significantly improved quality of life on the Skindex-29 Symptoms (P less than .05), Skindex-29 Function (P less than 05), and FACT-G Functional Well-Being (P less than .05) quality of life scales, which is part of what earned it a breakthrough therapy designation, Dr. Kim said.
MAVORIC is the largest randomized study to compare systemic therapies in CTCL and the first to use PFS as the primary endpoint, Dr. Kim noted. Patients’ level of CCR4 expression was not a criterion for enrollment because CCR4 is consistently and highly expressed in this disease, she noted. Thus, using mogamulizumab to treat CTCL in the United States would not require CCR4 testing.
Joseph M. Connors, MD, who specializes in lymphoid cancers at the BC Cancer Agency, a division of the British Columbia Provincial Health Services Authority, and who was not involved in the study, agreed that these data represent real headway in treating CTCL.
“I can state unequivocally that we just haven’t had effective therapy for CTCL,” he said at the press briefing. “We’ve had treatments that might help patients feel somewhat better, but we’ve had no consensus on a treatment that is right for this disease. These data provide an opportunity to have that consensus. They could create a platform for making further progress.”
Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
SOURCE: Kim YH et al. ASH 2017 Abstract 817.
REPORTING FROM ASH 2017
Key clinical point: Mogamulizumab more than doubled median progression-free survival, compared with vorinostat in patients with previously treated cutaneous T-cell lymphoma.
Major finding: Median progression-free survival was 7.7 months vs. 3.1 months (HR, 0.53; 95% CI, 0.41 to 0.69; P less than .0001).
Data source: An open-label phase 3 trial of 372 patients with previously treated cutaneous T-cell lymphoma (MAVORIC).
Disclosures: Kyowa Kirin Pharmaceutical Development provided funding. Dr. Kim disclosed research and advisory relationships with Kyowa Kirin and ties to Millennium Pharmaceuticals, Seattle Genetics, Soligenix, and other companies.
Source: Kim YH et al. ASH 2017 Abstract 817.
Updated ZUMA-1 data show durable CAR-T responses in B-cell lymphomas
ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.
Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.
“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.
The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 106 cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.
The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant
Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.
Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.
The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.
In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.
The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.
At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.
The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.
The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.
Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.
Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.
Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.
In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”
They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).
In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.
ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.
SOURCE: Neelapu S et al. ASH 2017 Abstract 578.
ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.
Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.
“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.
The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 106 cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.
The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant
Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.
Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.
The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.
In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.
The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.
At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.
The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.
The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.
Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.
Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.
Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.
In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”
They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).
In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.
ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.
SOURCE: Neelapu S et al. ASH 2017 Abstract 578.
ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.
Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.
“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.
The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 106 cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.
The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant
Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.
Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.
The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.
In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.
The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.
At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.
The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.
The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.
Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.
Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.
Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.
In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”
They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).
In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.
ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.
SOURCE: Neelapu S et al. ASH 2017 Abstract 578.
REPORTING FROM ASH 2017
Key clinical point:.
Major finding: The objective response rate was 82%, including 58% complete responses at a median of 15.4 months of follow-up.
Data source: Update analysis of phase 1 and 2 data from the ZUMA-1 trial in 108 patients with large B-cell lymphomas.
Disclosures: ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.
Source: Neelapu S et al. ASH 2017 Abstract 578
Hyperbaric oxygen may cut CO deaths
In patients with carbon monoxide poisoning, hyperbaric oxygen therapy was associated with a lower rate of mortality, according to results of a recent retrospective study.
The mortality reduction was particularly evident among patients under 20 years of age and in patients with acute respiratory failure, authors of the study said in a report published in Chest (2017 Nov. doi: 10.1016/j.chest.2017.03.049).
“The results provide important references for decision making in the treatment of carbon monoxide poisoning,” Chien-Cheng Huang, MD, department of emergency medicine, Chi-Mei Medical Center, Tainan, Taiwan, and colleagues said in their report.
While hyperbaric oxygen has been suggested for severe carbon monoxide poisoning, 100% normobaric oxygen is considered standard treatment, according to Dr. Huang and colleagues.
“There has been no consensus about whether hyperbaric oxygen therapy is better than 100% normobaric oxygen alone, or the number of sessions of hyperbaric oxygen therapy that are necessary regarding mortality and morbidity,” they wrote.
In a Taiwanese nationwide poisoning database, Dr. Huang and colleagues identified 25,737 patients diagnosed with carbon monoxide poisoning between 1999 and 2012. Of those patients, 7,278 had hyperbaric oxygen therapy.
After researchers adjusted for variables including age, sex, and underlying comorbidities, the mortality rate was lower in patients who underwent hyperbaric oxygen therapy, compared with those who did not (adjusted hazard ratio, 0.74; 95% confidence interval, 0.67-0.81), data show.
The reduction in mortality was especially notable in patients younger than age 20 years (adjusted HR, 0.45; 95% CI, 0.26-0.80), according to the researchers.
A similarly greater magnitude of mortality benefit also was found for patients who had acute respiratory failure, “which supports acute respiratory failure being an indication for hyperbaric oxygen therapy,” investigators wrote. “Further studies are warranted to clarify this issue.”
The number of hyperbaric oxygen therapy sessions appeared to make a difference in mortality. Patients who received two or more sessions had a lower rate of mortality than did those who had only one session, according to the report.
Predictors of mortality, described in more detail in the published report, included older age, diabetes, alcoholism, and suicide attempts, among other factors.
“In addition to considering hyperbaric oxygen therapy for reducing mortality, control of other concomitant mortality predictors is necessary,” the authors concluded based on their results.
Accidental deaths from carbon monoxide poisoning also are a major issue in the United States, where each year, there are an estimated 1,000-2,000 cases, according to the authors. Additionally, accidental carbon monoxide poisoning has “increased greatly in the past 10 years,” they said in the report.
Other studies have shown that, compared with normobaric oxygen, hyperbaric oxygen therapy did not reduce neurologic complications, the authors noted. Even so, that fact “does not suggest that hyperbaric oxygen therapy is not beneficial regarding mortality,” they wrote. “In fact, it is possible that reducing mortality may increase morbidities such as neurologic sequelae.”
Dr. Huang and coauthors reported no conflicts of interest related to the study, which was supported by Chi-Mei Medical Center in Taiwan.
Use of hyperbaric oxygen therapy to treat carbon monoxide poisioning has been “controversial since its inception” since early promoters “tended to place hyperbaric treatment ahead of strong supporting data,” wrote Clayton T. Cowl, MD, FCCP, in an editorial regarding the study by Dr. Huang and colleagues.
These data are compelling because they come from what is believed to be the first large-scale study that specifically examines mortality as an endpoint in an entire nation, as opposed to smaller cohorts in single centers or even multiple institutions, he said in his editorial.
“Have we reached the point of clearly establishing that delivery of pure oxygen in a high-pressure environment is more effective in treating patients who have carbon monoxide poisoning than is normobaric supplemental oxygen alone? Probably not,” Dr. Cowl wrote.
“The retrospective database study by Huang et al, despite its large size and interesting findings, remains distant from the ideal of a large blinded multicenter randomized controlled trial using a standardized protocol to compare normobaric supplemental oxygenation with hyperbaric oxygen therapy delivery for this cohort,” he explained. “However, its size, scale, and findings add credibility to the mounting data supporting HBOT for this indication.”
Clayton T. Cowl, MD, FCCP, is with the division of preventive, occupational, and aerospace medicine and the division of pulmonary and critical care medicine, Mayo Clinic. His comments came from an editorial in Chest (doi: 10.1016/j.chest.2017.07.022) He declared no financial or nonfinancial disclosures related to the editorial.
Use of hyperbaric oxygen therapy to treat carbon monoxide poisioning has been “controversial since its inception” since early promoters “tended to place hyperbaric treatment ahead of strong supporting data,” wrote Clayton T. Cowl, MD, FCCP, in an editorial regarding the study by Dr. Huang and colleagues.
These data are compelling because they come from what is believed to be the first large-scale study that specifically examines mortality as an endpoint in an entire nation, as opposed to smaller cohorts in single centers or even multiple institutions, he said in his editorial.
“Have we reached the point of clearly establishing that delivery of pure oxygen in a high-pressure environment is more effective in treating patients who have carbon monoxide poisoning than is normobaric supplemental oxygen alone? Probably not,” Dr. Cowl wrote.
“The retrospective database study by Huang et al, despite its large size and interesting findings, remains distant from the ideal of a large blinded multicenter randomized controlled trial using a standardized protocol to compare normobaric supplemental oxygenation with hyperbaric oxygen therapy delivery for this cohort,” he explained. “However, its size, scale, and findings add credibility to the mounting data supporting HBOT for this indication.”
Clayton T. Cowl, MD, FCCP, is with the division of preventive, occupational, and aerospace medicine and the division of pulmonary and critical care medicine, Mayo Clinic. His comments came from an editorial in Chest (doi: 10.1016/j.chest.2017.07.022) He declared no financial or nonfinancial disclosures related to the editorial.
Use of hyperbaric oxygen therapy to treat carbon monoxide poisioning has been “controversial since its inception” since early promoters “tended to place hyperbaric treatment ahead of strong supporting data,” wrote Clayton T. Cowl, MD, FCCP, in an editorial regarding the study by Dr. Huang and colleagues.
These data are compelling because they come from what is believed to be the first large-scale study that specifically examines mortality as an endpoint in an entire nation, as opposed to smaller cohorts in single centers or even multiple institutions, he said in his editorial.
“Have we reached the point of clearly establishing that delivery of pure oxygen in a high-pressure environment is more effective in treating patients who have carbon monoxide poisoning than is normobaric supplemental oxygen alone? Probably not,” Dr. Cowl wrote.
“The retrospective database study by Huang et al, despite its large size and interesting findings, remains distant from the ideal of a large blinded multicenter randomized controlled trial using a standardized protocol to compare normobaric supplemental oxygenation with hyperbaric oxygen therapy delivery for this cohort,” he explained. “However, its size, scale, and findings add credibility to the mounting data supporting HBOT for this indication.”
Clayton T. Cowl, MD, FCCP, is with the division of preventive, occupational, and aerospace medicine and the division of pulmonary and critical care medicine, Mayo Clinic. His comments came from an editorial in Chest (doi: 10.1016/j.chest.2017.07.022) He declared no financial or nonfinancial disclosures related to the editorial.
In patients with carbon monoxide poisoning, hyperbaric oxygen therapy was associated with a lower rate of mortality, according to results of a recent retrospective study.
The mortality reduction was particularly evident among patients under 20 years of age and in patients with acute respiratory failure, authors of the study said in a report published in Chest (2017 Nov. doi: 10.1016/j.chest.2017.03.049).
“The results provide important references for decision making in the treatment of carbon monoxide poisoning,” Chien-Cheng Huang, MD, department of emergency medicine, Chi-Mei Medical Center, Tainan, Taiwan, and colleagues said in their report.
While hyperbaric oxygen has been suggested for severe carbon monoxide poisoning, 100% normobaric oxygen is considered standard treatment, according to Dr. Huang and colleagues.
“There has been no consensus about whether hyperbaric oxygen therapy is better than 100% normobaric oxygen alone, or the number of sessions of hyperbaric oxygen therapy that are necessary regarding mortality and morbidity,” they wrote.
In a Taiwanese nationwide poisoning database, Dr. Huang and colleagues identified 25,737 patients diagnosed with carbon monoxide poisoning between 1999 and 2012. Of those patients, 7,278 had hyperbaric oxygen therapy.
After researchers adjusted for variables including age, sex, and underlying comorbidities, the mortality rate was lower in patients who underwent hyperbaric oxygen therapy, compared with those who did not (adjusted hazard ratio, 0.74; 95% confidence interval, 0.67-0.81), data show.
The reduction in mortality was especially notable in patients younger than age 20 years (adjusted HR, 0.45; 95% CI, 0.26-0.80), according to the researchers.
A similarly greater magnitude of mortality benefit also was found for patients who had acute respiratory failure, “which supports acute respiratory failure being an indication for hyperbaric oxygen therapy,” investigators wrote. “Further studies are warranted to clarify this issue.”
The number of hyperbaric oxygen therapy sessions appeared to make a difference in mortality. Patients who received two or more sessions had a lower rate of mortality than did those who had only one session, according to the report.
Predictors of mortality, described in more detail in the published report, included older age, diabetes, alcoholism, and suicide attempts, among other factors.
“In addition to considering hyperbaric oxygen therapy for reducing mortality, control of other concomitant mortality predictors is necessary,” the authors concluded based on their results.
Accidental deaths from carbon monoxide poisoning also are a major issue in the United States, where each year, there are an estimated 1,000-2,000 cases, according to the authors. Additionally, accidental carbon monoxide poisoning has “increased greatly in the past 10 years,” they said in the report.
Other studies have shown that, compared with normobaric oxygen, hyperbaric oxygen therapy did not reduce neurologic complications, the authors noted. Even so, that fact “does not suggest that hyperbaric oxygen therapy is not beneficial regarding mortality,” they wrote. “In fact, it is possible that reducing mortality may increase morbidities such as neurologic sequelae.”
Dr. Huang and coauthors reported no conflicts of interest related to the study, which was supported by Chi-Mei Medical Center in Taiwan.
In patients with carbon monoxide poisoning, hyperbaric oxygen therapy was associated with a lower rate of mortality, according to results of a recent retrospective study.
The mortality reduction was particularly evident among patients under 20 years of age and in patients with acute respiratory failure, authors of the study said in a report published in Chest (2017 Nov. doi: 10.1016/j.chest.2017.03.049).
“The results provide important references for decision making in the treatment of carbon monoxide poisoning,” Chien-Cheng Huang, MD, department of emergency medicine, Chi-Mei Medical Center, Tainan, Taiwan, and colleagues said in their report.
While hyperbaric oxygen has been suggested for severe carbon monoxide poisoning, 100% normobaric oxygen is considered standard treatment, according to Dr. Huang and colleagues.
“There has been no consensus about whether hyperbaric oxygen therapy is better than 100% normobaric oxygen alone, or the number of sessions of hyperbaric oxygen therapy that are necessary regarding mortality and morbidity,” they wrote.
In a Taiwanese nationwide poisoning database, Dr. Huang and colleagues identified 25,737 patients diagnosed with carbon monoxide poisoning between 1999 and 2012. Of those patients, 7,278 had hyperbaric oxygen therapy.
After researchers adjusted for variables including age, sex, and underlying comorbidities, the mortality rate was lower in patients who underwent hyperbaric oxygen therapy, compared with those who did not (adjusted hazard ratio, 0.74; 95% confidence interval, 0.67-0.81), data show.
The reduction in mortality was especially notable in patients younger than age 20 years (adjusted HR, 0.45; 95% CI, 0.26-0.80), according to the researchers.
A similarly greater magnitude of mortality benefit also was found for patients who had acute respiratory failure, “which supports acute respiratory failure being an indication for hyperbaric oxygen therapy,” investigators wrote. “Further studies are warranted to clarify this issue.”
The number of hyperbaric oxygen therapy sessions appeared to make a difference in mortality. Patients who received two or more sessions had a lower rate of mortality than did those who had only one session, according to the report.
Predictors of mortality, described in more detail in the published report, included older age, diabetes, alcoholism, and suicide attempts, among other factors.
“In addition to considering hyperbaric oxygen therapy for reducing mortality, control of other concomitant mortality predictors is necessary,” the authors concluded based on their results.
Accidental deaths from carbon monoxide poisoning also are a major issue in the United States, where each year, there are an estimated 1,000-2,000 cases, according to the authors. Additionally, accidental carbon monoxide poisoning has “increased greatly in the past 10 years,” they said in the report.
Other studies have shown that, compared with normobaric oxygen, hyperbaric oxygen therapy did not reduce neurologic complications, the authors noted. Even so, that fact “does not suggest that hyperbaric oxygen therapy is not beneficial regarding mortality,” they wrote. “In fact, it is possible that reducing mortality may increase morbidities such as neurologic sequelae.”
Dr. Huang and coauthors reported no conflicts of interest related to the study, which was supported by Chi-Mei Medical Center in Taiwan.
FROM CHEST
Key clinical point: In patients with carbon monoxide poisoning, hyperbaric oxygen therapy was associated with a lower rate of mortality.
Major finding: The mortality rate was lower in patients who received hyperbaric oxygen therapy, compared with those who did not (adjusted HR, 0.74; 95% CI, 0.67-0.81).
Data source: A retrospective nationwide population-based study from Taiwan including 25,737 individuals diagnosed with carbon monoxide poisoning during 1999-2012.
Disclosures: Chi-Mei Medical Center in Taiwan supported the study. The authors reported no conflicts of interest.