ORLANDO – Tocilizumab plus standard immune suppression appears to drive down the risk for graft-versus-host disease (GVHD), according to results from a phase II study of 35 adults undergoing allogeneic stem cell transplants.

The effect was particularly pronounced for prevention of GVHD in the colon, William Drobyski, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The incidence rate of grades II-IV and III-IV acute GVHD was 12% at day 100 in patients given standard prophylaxis of tacrolimus/methotrexate (Tac/MTX) and 3% in patients given Tac/MTX plus 8 mg/kg of tocilizumab (Toc, capped at 800 mg), said Dr. Drobyski of the Medical College of Wisconsin, Milwaukee.

To provide further context to the results, Dr. Drobyski and his colleagues performed a matched case-control analysis using contemporary controls in the Center for International Blood & Marrow Transplant Research from 2000 to 2014. The same eligibility criteria used for the trial were applied to the matched controls except for the use of Tac/MTX as GVHD prophylaxis. Patients were otherwise matched based on age, performance score, disease, and donor type.

The incidence of grades II-IV acute GVHD at day 100 was significantly lower in the Toc/Tac/MTX group than in the Tac/MTX control population (12% vs. 41%). The incidence of grades III-IV acute GVHD was slightly lower with tocilizumab, but the difference between the groups was not statistically significant, Dr. Drobyski said.

The probability of grade II-IV acute GVHD–free survival, which was the primary endpoint of the study, was significantly higher in the Toc/Tac/MTX group (79% vs 52%), he said.

Five patients developed grade 2 acute GVHD of the skin or upper GI tract, and one patient died of grade 4 acute GVHD of the skin in the first 100 days. Notably, there were no cases of acute GVHD of the lower GI tract during that time, although two cases did occur between days 130 and 180, he said.

“There was no difference in transplant-related mortality, relapse, disease-free survival, or overall survival,” he said, adding that preliminary data suggest there were no differences in chronic GVHD between the groups.

Causes of death also were similar between the two cohorts with respect to disease- and transplant-related complications.

Patients in the tocilizumab study were enrolled between January 2015 and June 2016; the median age was 66 years. Diseases represented in the cohort included de novo acute myeloid leukemia (13 patients), AML (6 patients), chronic myelomonocytic leukemia (6 patients), acute lymphoblastic leukemia (4 patients), myelodysplastic syndrome (3 patients), and T-cell lymphoma, chronic myeloid leukemia, and NK/T cell lymphoma (in 1 patient each). Most patients were classified as high risk (9 patients) or intermediate risk (22 patients) by the disease risk index.

Conditioning was entirely busulfan based. Myeloablative conditioning was with busulfan and cyclophosphamide (Cytoxan) in 5 patients, or fludarabine and 4 days of busulfan in 10 patients, and reduced-intensity conditioning was with fludarabine and 2 days of busulfan in 18 patients. Transplants were with either HLA-matched related or unrelated donor grafts. Most patients (29 of 35) received peripheral stem cell grafts.

Tocilizumab, an interleuken-6 receptor blocker that is approved for treatment of rheumatoid arthritis, was administered after completion of conditioning and on the day prior to stem cell infusion.

In a pilot clinical trial of tocilizumab for the treatment of steroid-resistant acute GVHD in patients who had primarily had lower GI tract disease, “we were able to demonstrate responses in a majority of these patients,” Dr. Drobyski said, noting that a recent study presented at the 2016 annual meeting of the American Society of Hematology also showed efficacy in the treatment of lower tract GI GVHD, “providing evidence that tocilizumab had activity in acute GVHD, and perhaps in the treatment of steroid-refractory lower GI GVHD.”

Elevated IL-6 levels in the peripheral blood are correlated with an increased incidence and severity of GVHD; administration of an anti-IL-6 receptor antibody has been shown in preclinical studies to protect mice from lethal GVHD. The current open-label study was performed to “try to advance this concept” by assessing whether inhibition of IL-6 signaling could also prevent acute GVHD.

The findings confirm those of a 2014 study by Kennedy et al. in Lancet Oncology (2014;15:1451-9), and imply that tocilizumab warrants a randomized trial as prophylaxis for acute GVHD, he concluded.

Dr. Drobyski reported having no disclosures.

[email protected]

ORLANDO – Tocilizumab plus standard immune suppression appears to drive down the risk for graft-versus-host disease (GVHD), according to results from a phase II study of 35 adults undergoing allogeneic stem cell transplants.

The effect was particularly pronounced for prevention of GVHD in the colon, William Drobyski, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The incidence rate of grades II-IV and III-IV acute GVHD was 12% at day 100 in patients given standard prophylaxis of tacrolimus/methotrexate (Tac/MTX) and 3% in patients given Tac/MTX plus 8 mg/kg of tocilizumab (Toc, capped at 800 mg), said Dr. Drobyski of the Medical College of Wisconsin, Milwaukee.

To provide further context to the results, Dr. Drobyski and his colleagues performed a matched case-control analysis using contemporary controls in the Center for International Blood & Marrow Transplant Research from 2000 to 2014. The same eligibility criteria used for the trial were applied to the matched controls except for the use of Tac/MTX as GVHD prophylaxis. Patients were otherwise matched based on age, performance score, disease, and donor type.

The incidence of grades II-IV acute GVHD at day 100 was significantly lower in the Toc/Tac/MTX group than in the Tac/MTX control population (12% vs. 41%). The incidence of grades III-IV acute GVHD was slightly lower with tocilizumab, but the difference between the groups was not statistically significant, Dr. Drobyski said.

The probability of grade II-IV acute GVHD–free survival, which was the primary endpoint of the study, was significantly higher in the Toc/Tac/MTX group (79% vs 52%), he said.

Five patients developed grade 2 acute GVHD of the skin or upper GI tract, and one patient died of grade 4 acute GVHD of the skin in the first 100 days. Notably, there were no cases of acute GVHD of the lower GI tract during that time, although two cases did occur between days 130 and 180, he said.

“There was no difference in transplant-related mortality, relapse, disease-free survival, or overall survival,” he said, adding that preliminary data suggest there were no differences in chronic GVHD between the groups.

Causes of death also were similar between the two cohorts with respect to disease- and transplant-related complications.

Patients in the tocilizumab study were enrolled between January 2015 and June 2016; the median age was 66 years. Diseases represented in the cohort included de novo acute myeloid leukemia (13 patients), AML (6 patients), chronic myelomonocytic leukemia (6 patients), acute lymphoblastic leukemia (4 patients), myelodysplastic syndrome (3 patients), and T-cell lymphoma, chronic myeloid leukemia, and NK/T cell lymphoma (in 1 patient each). Most patients were classified as high risk (9 patients) or intermediate risk (22 patients) by the disease risk index.

Conditioning was entirely busulfan based. Myeloablative conditioning was with busulfan and cyclophosphamide (Cytoxan) in 5 patients, or fludarabine and 4 days of busulfan in 10 patients, and reduced-intensity conditioning was with fludarabine and 2 days of busulfan in 18 patients. Transplants were with either HLA-matched related or unrelated donor grafts. Most patients (29 of 35) received peripheral stem cell grafts.

Tocilizumab, an interleuken-6 receptor blocker that is approved for treatment of rheumatoid arthritis, was administered after completion of conditioning and on the day prior to stem cell infusion.

In a pilot clinical trial of tocilizumab for the treatment of steroid-resistant acute GVHD in patients who had primarily had lower GI tract disease, “we were able to demonstrate responses in a majority of these patients,” Dr. Drobyski said, noting that a recent study presented at the 2016 annual meeting of the American Society of Hematology also showed efficacy in the treatment of lower tract GI GVHD, “providing evidence that tocilizumab had activity in acute GVHD, and perhaps in the treatment of steroid-refractory lower GI GVHD.”

Elevated IL-6 levels in the peripheral blood are correlated with an increased incidence and severity of GVHD; administration of an anti-IL-6 receptor antibody has been shown in preclinical studies to protect mice from lethal GVHD. The current open-label study was performed to “try to advance this concept” by assessing whether inhibition of IL-6 signaling could also prevent acute GVHD.

The findings confirm those of a 2014 study by Kennedy et al. in Lancet Oncology (2014;15:1451-9), and imply that tocilizumab warrants a randomized trial as prophylaxis for acute GVHD, he concluded.

Dr. Drobyski reported having no disclosures.

[email protected]

ORLANDO – Tocilizumab plus standard immune suppression appears to drive down the risk for graft-versus-host disease (GVHD), according to results from a phase II study of 35 adults undergoing allogeneic stem cell transplants.

The effect was particularly pronounced for prevention of GVHD in the colon, William Drobyski, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The incidence rate of grades II-IV and III-IV acute GVHD was 12% at day 100 in patients given standard prophylaxis of tacrolimus/methotrexate (Tac/MTX) and 3% in patients given Tac/MTX plus 8 mg/kg of tocilizumab (Toc, capped at 800 mg), said Dr. Drobyski of the Medical College of Wisconsin, Milwaukee.

To provide further context to the results, Dr. Drobyski and his colleagues performed a matched case-control analysis using contemporary controls in the Center for International Blood & Marrow Transplant Research from 2000 to 2014. The same eligibility criteria used for the trial were applied to the matched controls except for the use of Tac/MTX as GVHD prophylaxis. Patients were otherwise matched based on age, performance score, disease, and donor type.

The incidence of grades II-IV acute GVHD at day 100 was significantly lower in the Toc/Tac/MTX group than in the Tac/MTX control population (12% vs. 41%). The incidence of grades III-IV acute GVHD was slightly lower with tocilizumab, but the difference between the groups was not statistically significant, Dr. Drobyski said.

The probability of grade II-IV acute GVHD–free survival, which was the primary endpoint of the study, was significantly higher in the Toc/Tac/MTX group (79% vs 52%), he said.

Five patients developed grade 2 acute GVHD of the skin or upper GI tract, and one patient died of grade 4 acute GVHD of the skin in the first 100 days. Notably, there were no cases of acute GVHD of the lower GI tract during that time, although two cases did occur between days 130 and 180, he said.

“There was no difference in transplant-related mortality, relapse, disease-free survival, or overall survival,” he said, adding that preliminary data suggest there were no differences in chronic GVHD between the groups.

Causes of death also were similar between the two cohorts with respect to disease- and transplant-related complications.

Patients in the tocilizumab study were enrolled between January 2015 and June 2016; the median age was 66 years. Diseases represented in the cohort included de novo acute myeloid leukemia (13 patients), AML (6 patients), chronic myelomonocytic leukemia (6 patients), acute lymphoblastic leukemia (4 patients), myelodysplastic syndrome (3 patients), and T-cell lymphoma, chronic myeloid leukemia, and NK/T cell lymphoma (in 1 patient each). Most patients were classified as high risk (9 patients) or intermediate risk (22 patients) by the disease risk index.

Conditioning was entirely busulfan based. Myeloablative conditioning was with busulfan and cyclophosphamide (Cytoxan) in 5 patients, or fludarabine and 4 days of busulfan in 10 patients, and reduced-intensity conditioning was with fludarabine and 2 days of busulfan in 18 patients. Transplants were with either HLA-matched related or unrelated donor grafts. Most patients (29 of 35) received peripheral stem cell grafts.

Tocilizumab, an interleuken-6 receptor blocker that is approved for treatment of rheumatoid arthritis, was administered after completion of conditioning and on the day prior to stem cell infusion.

In a pilot clinical trial of tocilizumab for the treatment of steroid-resistant acute GVHD in patients who had primarily had lower GI tract disease, “we were able to demonstrate responses in a majority of these patients,” Dr. Drobyski said, noting that a recent study presented at the 2016 annual meeting of the American Society of Hematology also showed efficacy in the treatment of lower tract GI GVHD, “providing evidence that tocilizumab had activity in acute GVHD, and perhaps in the treatment of steroid-refractory lower GI GVHD.”

Elevated IL-6 levels in the peripheral blood are correlated with an increased incidence and severity of GVHD; administration of an anti-IL-6 receptor antibody has been shown in preclinical studies to protect mice from lethal GVHD. The current open-label study was performed to “try to advance this concept” by assessing whether inhibition of IL-6 signaling could also prevent acute GVHD.

The findings confirm those of a 2014 study by Kennedy et al. in Lancet Oncology (2014;15:1451-9), and imply that tocilizumab warrants a randomized trial as prophylaxis for acute GVHD, he concluded.

Dr. Drobyski reported having no disclosures.

[email protected]

Hepatitis B and C appear to raise the risk of later Parkinson’s disease (PD), according to a report published in Neurology.

The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, have been proposed that may increase risk for the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s risk, said Julia Pakpoor, BM BCh, of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford (England), and her associates.

To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999-2011. They assessed the risk for developing PD among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.

The risk of developing PD was elevated for only 1 or more years following hospitalization for hepatitis B (relative risk, 1.76) or hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said (Neurology. 2017;88:1-4).

The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium. … suggesting one mechanism by which the virus may affect the CNS,” they noted.

In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis, and cirrhosis status was not available for the members of this study cohort.

More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of PD, “which may be important to understanding the development of PD more broadly,” Dr. Pakpoor and her associates said.

The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.

Hepatitis B and C appear to raise the risk of later Parkinson’s disease (PD), according to a report published in Neurology.

The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, have been proposed that may increase risk for the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s risk, said Julia Pakpoor, BM BCh, of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford (England), and her associates.

To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999-2011. They assessed the risk for developing PD among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.

The risk of developing PD was elevated for only 1 or more years following hospitalization for hepatitis B (relative risk, 1.76) or hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said (Neurology. 2017;88:1-4).

The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium. … suggesting one mechanism by which the virus may affect the CNS,” they noted.

In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis, and cirrhosis status was not available for the members of this study cohort.

More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of PD, “which may be important to understanding the development of PD more broadly,” Dr. Pakpoor and her associates said.

The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.

Hepatitis B and C appear to raise the risk of later Parkinson’s disease (PD), according to a report published in Neurology.

The etiology of Parkinson’s disease is complex, and several factors, including environmental toxins and head trauma, have been proposed that may increase risk for the disorder. Two recent epidemiologic studies in Taiwan found an association between hepatitis C and Parkinson’s risk, said Julia Pakpoor, BM BCh, of the Unit of Health-Care Epidemiology, Nuffield Department of Population Health, University of Oxford (England), and her associates.

To further explore that association, the investigators performed a retrospective cohort study using data from National Health Service hospitals across England for 1999-2011. They assessed the risk for developing PD among 21,633 people with hepatitis B, 48,428 with hepatitis C, 6,225 with autoimmune hepatitis, 4,234 with chronic active hepatitis, 19,870 with HIV, and 6,132,124 control subjects with other disorders.

The risk of developing PD was elevated for only 1 or more years following hospitalization for hepatitis B (relative risk, 1.76) or hepatitis C (RR, 1.51). “These findings may be explained by a specific aspect of viral hepatitis (rather than a general hepatic inflammatory process or general use of antivirals), but whether this reflects shared disease mechanisms, shared genetic or environmental susceptibility, sequelae of viral hepatitis per se, or a consequence of treatment remains to be determined,” Dr. Pakpoor and her associates said (Neurology. 2017;88:1-4).

The reason for this association is not yet known. “Neurotropic features of hepatitis C have been described previously and include the potential for cognitive impairment, independent of hepatic encephalopathy. Further, all essential hepatitis C virus receptors have been shown to be expressed on the brain microvascular endothelium. … suggesting one mechanism by which the virus may affect the CNS,” they noted.

In addition, parkinsonism has been described as an adverse effect of treatment with interferon and ribavirin, which are commonly used in hepatitis C infection. Parkinsonism also is known to develop in association with liver cirrhosis, and cirrhosis status was not available for the members of this study cohort.

More studies are needed to confirm this association and verify that it is causal. Such research will also provide insight into pathophysiologic pathways of PD, “which may be important to understanding the development of PD more broadly,” Dr. Pakpoor and her associates said.

The English National Institute for Health Research supported the study. Dr. Pakpoor and her associates reported having no relevant financial disclosures.

One of the most enduring lessons I have learned during my time in hospital medicine is that hospitalists are always evolving, much like the specialty and healthcare system of which they are a part. And during my time as president of the Society of Hospital Medicine (SHM), I have come to realize how SHM provides its members with the resources to help us continue that evolution through our career journeys as a part of the hospital medicine movement.

Over a year ago, I ascended to president of SHM’s board of directors at HM16, the annual meeting in San Diego. Now, I am eagerly looking forward to HM17 next month, in Las Vegas, which we expect to be, yet again, the biggest, best, most innovative and most energetic gathering of hospitalists. As that meeting will mark the end of my tenure as president of the board, I’m also inclined to look back and survey what has happened over the last year, both personally and professionally.

In sum

As I prepare to the pass to baton to Dr. Ron Greeno for 2017-18, I am reminded of one of the pearls of a former boss and mentor of mine who preached that career satisfaction comes from finding opportunities to achieve three goals: addressing meaningful challenges, working with compelling individuals, and learning something new every day. I would like to thank the board, SHM CEO Larry Wellikson, MD, MHM, and the society staff and volunteers, and, most of all, the many SHM members with whom I have met and spoken over the last year for providing me with exactly that opportunity.

I look forward to continuing to serve an active role in SHM, an organization that can provide you with those same opportunities and resources to help you grow, evolve and be an active participant in the hospital medicine movement.

One of the most enduring lessons I have learned during my time in hospital medicine is that hospitalists are always evolving, much like the specialty and healthcare system of which they are a part. And during my time as president of the Society of Hospital Medicine (SHM), I have come to realize how SHM provides its members with the resources to help us continue that evolution through our career journeys as a part of the hospital medicine movement.

Over a year ago, I ascended to president of SHM’s board of directors at HM16, the annual meeting in San Diego. Now, I am eagerly looking forward to HM17 next month, in Las Vegas, which we expect to be, yet again, the biggest, best, most innovative and most energetic gathering of hospitalists. As that meeting will mark the end of my tenure as president of the board, I’m also inclined to look back and survey what has happened over the last year, both personally and professionally.

In sum

As I prepare to the pass to baton to Dr. Ron Greeno for 2017-18, I am reminded of one of the pearls of a former boss and mentor of mine who preached that career satisfaction comes from finding opportunities to achieve three goals: addressing meaningful challenges, working with compelling individuals, and learning something new every day. I would like to thank the board, SHM CEO Larry Wellikson, MD, MHM, and the society staff and volunteers, and, most of all, the many SHM members with whom I have met and spoken over the last year for providing me with exactly that opportunity.

I look forward to continuing to serve an active role in SHM, an organization that can provide you with those same opportunities and resources to help you grow, evolve and be an active participant in the hospital medicine movement.

One of the most enduring lessons I have learned during my time in hospital medicine is that hospitalists are always evolving, much like the specialty and healthcare system of which they are a part. And during my time as president of the Society of Hospital Medicine (SHM), I have come to realize how SHM provides its members with the resources to help us continue that evolution through our career journeys as a part of the hospital medicine movement.

Over a year ago, I ascended to president of SHM’s board of directors at HM16, the annual meeting in San Diego. Now, I am eagerly looking forward to HM17 next month, in Las Vegas, which we expect to be, yet again, the biggest, best, most innovative and most energetic gathering of hospitalists. As that meeting will mark the end of my tenure as president of the board, I’m also inclined to look back and survey what has happened over the last year, both personally and professionally.

In sum

As I prepare to the pass to baton to Dr. Ron Greeno for 2017-18, I am reminded of one of the pearls of a former boss and mentor of mine who preached that career satisfaction comes from finding opportunities to achieve three goals: addressing meaningful challenges, working with compelling individuals, and learning something new every day. I would like to thank the board, SHM CEO Larry Wellikson, MD, MHM, and the society staff and volunteers, and, most of all, the many SHM members with whom I have met and spoken over the last year for providing me with exactly that opportunity.

I look forward to continuing to serve an active role in SHM, an organization that can provide you with those same opportunities and resources to help you grow, evolve and be an active participant in the hospital medicine movement.

In her February 2017 article, Lucia DiVenere interviewed the current and incoming ACOG Presidents, Drs. Thomas Gellhaus and Haywood Brown. The Presidents called for advocacy on behalf of the “melting pot” of women’s health specialists and subspecialists. “We cannot sit on the sidelines and expect others to speak for us,” said Dr. Gellhaus. “If we are not part of the solution, then we need to cede our future to others and have no right to complain about the result. Our members need to commit to advocating outside their exam rooms.”

Answer the poll below:

[polldaddy:9703185]

Click here to view Lucia DiVenere’s article
'What lies ahead for women’s health? Challenges and opportunities as ACOG and US leadership transition'

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In her February 2017 article, Lucia DiVenere interviewed the current and incoming ACOG Presidents, Drs. Thomas Gellhaus and Haywood Brown. The Presidents called for advocacy on behalf of the “melting pot” of women’s health specialists and subspecialists. “We cannot sit on the sidelines and expect others to speak for us,” said Dr. Gellhaus. “If we are not part of the solution, then we need to cede our future to others and have no right to complain about the result. Our members need to commit to advocating outside their exam rooms.”

Answer the poll below:

[polldaddy:9703185]

Click here to view Lucia DiVenere’s article
'What lies ahead for women’s health? Challenges and opportunities as ACOG and US leadership transition'

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In her February 2017 article, Lucia DiVenere interviewed the current and incoming ACOG Presidents, Drs. Thomas Gellhaus and Haywood Brown. The Presidents called for advocacy on behalf of the “melting pot” of women’s health specialists and subspecialists. “We cannot sit on the sidelines and expect others to speak for us,” said Dr. Gellhaus. “If we are not part of the solution, then we need to cede our future to others and have no right to complain about the result. Our members need to commit to advocating outside their exam rooms.”

Answer the poll below:

[polldaddy:9703185]

Click here to view Lucia DiVenere’s article
'What lies ahead for women’s health? Challenges and opportunities as ACOG and US leadership transition'

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Extramedullary plasmacytomas are rare ( > 5% of all plasma cell neoplasms), and the gastric version is even more rare. That rarity combined with unspecific symptoms that mimic other tumors “can mislead the clinician into a diagnosis of a more aggressive tumor,” say clinicians from University Hospital Center of Coimbra in Portugal. They reported on a patient who presented that diagnostic puzzle.

The patient arrived in the emergency department with symptoms of upper gastrointestinal bleeding. He had a history of tongue carcinoma, cirrhosis, diabetes mellitus, chronic gastritis, and obesity, among other health conditions, and was taking a panoply of medications. The patient’s family history included a grandmother with breast cancer and an aunt with head and neck cancer.

Related: Treatment and Management of Multiple Myeloma

The clinicians embarked on an extensive diagnostic process of elimination. Endoscopy, immunohistochemistry, and other tests helped rule out Helicobacter pylori infection, lymphoma, carcinoma, melanoma, and neuroendocrine carcinoma. “Rethinking our possibilities,” the clinicians say, and taking into account the presence of mature and immature plasmocytes in the periphery, they next considered plasmacytoma/multiple myeloma (MM). On the third immunohistochemical panel, they got the evidence they needed for the diagnosis: gastric plasmacytoma (GP)/ involvement by MM.

Gastric plasmacytomas have a good prognosis. Surgical excision normally is the treatment of choice with good results, the clinicians say. After endoscopic polypectomy without radiation, the patient was discharged with no further therapy. Although diagnosed with prostate cancer in the 6 years following, the patient has had no signs of plasmacytic relapse.

Related: Rare Cancer Gets Timely Right Treatment

Due to their cellular similarity, GP needs to be differentiated from MM. But GP may be the initial manifestation of a MM, the clinicians note. Therefore, the patient must undergo systemic evaluation to exclude bone marrow involvement and to make sure there is no clinical or laboratory evidence of myeloma.

Sources:

1. Oliveira RC, Amaro P, Julião MJ, Cipriano MA. BMJ Case Rep. 2017. pii: bcr2016218967.
doi: 10.1136/bcr-2016-218967.

2. International Myeloma Working Group. Br J Haematol. 2003;12(5):749-57.
doi: 10.1046/j.1365-2141.2003.04355.x

3. Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary

plasmacytoma of bone and extramedullary plasmacytoma. Sci World J. 2012;2012:895765.
doi: 10.1100/2012/895765.

Extramedullary plasmacytomas are rare ( > 5% of all plasma cell neoplasms), and the gastric version is even more rare. That rarity combined with unspecific symptoms that mimic other tumors “can mislead the clinician into a diagnosis of a more aggressive tumor,” say clinicians from University Hospital Center of Coimbra in Portugal. They reported on a patient who presented that diagnostic puzzle.

The patient arrived in the emergency department with symptoms of upper gastrointestinal bleeding. He had a history of tongue carcinoma, cirrhosis, diabetes mellitus, chronic gastritis, and obesity, among other health conditions, and was taking a panoply of medications. The patient’s family history included a grandmother with breast cancer and an aunt with head and neck cancer.

Related: Treatment and Management of Multiple Myeloma

The clinicians embarked on an extensive diagnostic process of elimination. Endoscopy, immunohistochemistry, and other tests helped rule out Helicobacter pylori infection, lymphoma, carcinoma, melanoma, and neuroendocrine carcinoma. “Rethinking our possibilities,” the clinicians say, and taking into account the presence of mature and immature plasmocytes in the periphery, they next considered plasmacytoma/multiple myeloma (MM). On the third immunohistochemical panel, they got the evidence they needed for the diagnosis: gastric plasmacytoma (GP)/ involvement by MM.

Gastric plasmacytomas have a good prognosis. Surgical excision normally is the treatment of choice with good results, the clinicians say. After endoscopic polypectomy without radiation, the patient was discharged with no further therapy. Although diagnosed with prostate cancer in the 6 years following, the patient has had no signs of plasmacytic relapse.

Related: Rare Cancer Gets Timely Right Treatment

Due to their cellular similarity, GP needs to be differentiated from MM. But GP may be the initial manifestation of a MM, the clinicians note. Therefore, the patient must undergo systemic evaluation to exclude bone marrow involvement and to make sure there is no clinical or laboratory evidence of myeloma.

Sources:

1. Oliveira RC, Amaro P, Julião MJ, Cipriano MA. BMJ Case Rep. 2017. pii: bcr2016218967.
doi: 10.1136/bcr-2016-218967.

2. International Myeloma Working Group. Br J Haematol. 2003;12(5):749-57.
doi: 10.1046/j.1365-2141.2003.04355.x

3. Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary

plasmacytoma of bone and extramedullary plasmacytoma. Sci World J. 2012;2012:895765.
doi: 10.1100/2012/895765.

Extramedullary plasmacytomas are rare ( > 5% of all plasma cell neoplasms), and the gastric version is even more rare. That rarity combined with unspecific symptoms that mimic other tumors “can mislead the clinician into a diagnosis of a more aggressive tumor,” say clinicians from University Hospital Center of Coimbra in Portugal. They reported on a patient who presented that diagnostic puzzle.

The patient arrived in the emergency department with symptoms of upper gastrointestinal bleeding. He had a history of tongue carcinoma, cirrhosis, diabetes mellitus, chronic gastritis, and obesity, among other health conditions, and was taking a panoply of medications. The patient’s family history included a grandmother with breast cancer and an aunt with head and neck cancer.

Related: Treatment and Management of Multiple Myeloma

The clinicians embarked on an extensive diagnostic process of elimination. Endoscopy, immunohistochemistry, and other tests helped rule out Helicobacter pylori infection, lymphoma, carcinoma, melanoma, and neuroendocrine carcinoma. “Rethinking our possibilities,” the clinicians say, and taking into account the presence of mature and immature plasmocytes in the periphery, they next considered plasmacytoma/multiple myeloma (MM). On the third immunohistochemical panel, they got the evidence they needed for the diagnosis: gastric plasmacytoma (GP)/ involvement by MM.

Gastric plasmacytomas have a good prognosis. Surgical excision normally is the treatment of choice with good results, the clinicians say. After endoscopic polypectomy without radiation, the patient was discharged with no further therapy. Although diagnosed with prostate cancer in the 6 years following, the patient has had no signs of plasmacytic relapse.

Related: Rare Cancer Gets Timely Right Treatment

Due to their cellular similarity, GP needs to be differentiated from MM. But GP may be the initial manifestation of a MM, the clinicians note. Therefore, the patient must undergo systemic evaluation to exclude bone marrow involvement and to make sure there is no clinical or laboratory evidence of myeloma.

Sources:

1. Oliveira RC, Amaro P, Julião MJ, Cipriano MA. BMJ Case Rep. 2017. pii: bcr2016218967.
doi: 10.1136/bcr-2016-218967.

2. International Myeloma Working Group. Br J Haematol. 2003;12(5):749-57.
doi: 10.1046/j.1365-2141.2003.04355.x

3. Kilciksiz S, Karakoyun-Celik O, Agaoglu FY, Haydaroglu A. A review for solitary

plasmacytoma of bone and extramedullary plasmacytoma. Sci World J. 2012;2012:895765.
doi: 10.1100/2012/895765.

In 2015, the Texas Department of State Health Services was notified that a hospital telemetry unit nurse had been reusing saline flush prefilled syringes in patients’ IV lines. Mistakenly believing that it was safe and that she was saving the hospital money, she had been reusing syringes for 6 months.  This was not the hospital’s practice.

Because she had been putting patients at risk for bloodborne pathogens,  the state, regional, and local health departments with consultation from the CDC worked with the hospital to investigate. The hospital notified 392 patients, advising them of potential exposure and offering them free testing for hepatitis B (HBV), hepatitis C (HCV), and HIV. A year after the exposure, 262 had completed initial screening and 182 had completed all recommended testing.

Two patients had newly diagnosed HBV and 2 had HCV. A patient with known preexisting chronic HCV infection had been hospitalized on the telemetry unit on the same day as one of the patients with newly diagnosed HCV. That second patient did not share overlapping days with any patient with known HCV infection, nor did the 2 with newly diagnosed HBV infection share with each other or any other patient with a known HBV infection. No epidemiologic evidence linked the patients with newly diagnosed infections to a potential source patient. But when specimens were tested, the results indicated transmission linkage between the patient with chronic HCV infection and one of the patients with newly diagnosed HCV infection.

Taken together, the CDC concluded, the findings indicated that at least 1 HCV infection was “likely transmitted” in the telemetry unit as a result of the inappropriate reuse and sharing of syringes. The investigation, the CDC adds, illustrates a need for ongoing education and oversight of health care providers regarding safe injection practices.

In 2015, the Texas Department of State Health Services was notified that a hospital telemetry unit nurse had been reusing saline flush prefilled syringes in patients’ IV lines. Mistakenly believing that it was safe and that she was saving the hospital money, she had been reusing syringes for 6 months.  This was not the hospital’s practice.

Because she had been putting patients at risk for bloodborne pathogens,  the state, regional, and local health departments with consultation from the CDC worked with the hospital to investigate. The hospital notified 392 patients, advising them of potential exposure and offering them free testing for hepatitis B (HBV), hepatitis C (HCV), and HIV. A year after the exposure, 262 had completed initial screening and 182 had completed all recommended testing.

Two patients had newly diagnosed HBV and 2 had HCV. A patient with known preexisting chronic HCV infection had been hospitalized on the telemetry unit on the same day as one of the patients with newly diagnosed HCV. That second patient did not share overlapping days with any patient with known HCV infection, nor did the 2 with newly diagnosed HBV infection share with each other or any other patient with a known HBV infection. No epidemiologic evidence linked the patients with newly diagnosed infections to a potential source patient. But when specimens were tested, the results indicated transmission linkage between the patient with chronic HCV infection and one of the patients with newly diagnosed HCV infection.

Taken together, the CDC concluded, the findings indicated that at least 1 HCV infection was “likely transmitted” in the telemetry unit as a result of the inappropriate reuse and sharing of syringes. The investigation, the CDC adds, illustrates a need for ongoing education and oversight of health care providers regarding safe injection practices.

In 2015, the Texas Department of State Health Services was notified that a hospital telemetry unit nurse had been reusing saline flush prefilled syringes in patients’ IV lines. Mistakenly believing that it was safe and that she was saving the hospital money, she had been reusing syringes for 6 months.  This was not the hospital’s practice.

Because she had been putting patients at risk for bloodborne pathogens,  the state, regional, and local health departments with consultation from the CDC worked with the hospital to investigate. The hospital notified 392 patients, advising them of potential exposure and offering them free testing for hepatitis B (HBV), hepatitis C (HCV), and HIV. A year after the exposure, 262 had completed initial screening and 182 had completed all recommended testing.

Two patients had newly diagnosed HBV and 2 had HCV. A patient with known preexisting chronic HCV infection had been hospitalized on the telemetry unit on the same day as one of the patients with newly diagnosed HCV. That second patient did not share overlapping days with any patient with known HCV infection, nor did the 2 with newly diagnosed HBV infection share with each other or any other patient with a known HBV infection. No epidemiologic evidence linked the patients with newly diagnosed infections to a potential source patient. But when specimens were tested, the results indicated transmission linkage between the patient with chronic HCV infection and one of the patients with newly diagnosed HCV infection.

Taken together, the CDC concluded, the findings indicated that at least 1 HCV infection was “likely transmitted” in the telemetry unit as a result of the inappropriate reuse and sharing of syringes. The investigation, the CDC adds, illustrates a need for ongoing education and oversight of health care providers regarding safe injection practices.

Veterans who were exposed to contaminated water at Camp Lejeune are now eligible for VA care and benefits if they have been diagnosed with any of 8 diseases: adult leukemia, aplastic anemia and other myelodysplastic syndromes, bladder cancer, kidney cancer, liver cancer, multiple myeloma, non-Hodgkin lymphoma, and Parkinson disease. The presumption of service connection regulations went into effect March 14.

The newly effective rule complements the health care already provided for 15 illnesses or conditions as part of the Honoring America’s Veterans and Caring for Camp Lejeune Families Act of 2012. The Camp Lejeune Act requires the VA to provide health care to veterans who served at Camp Lejeune and to reimburse family members or pay providers for medical expenses for those who lived there for ≥ 30 days between August 1, 1953, and December 31, 1987.

The act and new rule relate to 2 on-base water wells that were contaminated with trichloroethylene, perchloroethylene, benzene, vinyl chloride, and other compounds. The wells were shut down in 1985.

The presumption of service connection applies to active-duty, reserve, and National Guard members. The presumption also includes all of Camp Lejeune, Marine Corps Air Station New River, as well as satellite camps and housing areas.

Veterans who were exposed to contaminated water at Camp Lejeune are now eligible for VA care and benefits if they have been diagnosed with any of 8 diseases: adult leukemia, aplastic anemia and other myelodysplastic syndromes, bladder cancer, kidney cancer, liver cancer, multiple myeloma, non-Hodgkin lymphoma, and Parkinson disease. The presumption of service connection regulations went into effect March 14.

The newly effective rule complements the health care already provided for 15 illnesses or conditions as part of the Honoring America’s Veterans and Caring for Camp Lejeune Families Act of 2012. The Camp Lejeune Act requires the VA to provide health care to veterans who served at Camp Lejeune and to reimburse family members or pay providers for medical expenses for those who lived there for ≥ 30 days between August 1, 1953, and December 31, 1987.

The act and new rule relate to 2 on-base water wells that were contaminated with trichloroethylene, perchloroethylene, benzene, vinyl chloride, and other compounds. The wells were shut down in 1985.

The presumption of service connection applies to active-duty, reserve, and National Guard members. The presumption also includes all of Camp Lejeune, Marine Corps Air Station New River, as well as satellite camps and housing areas.

Veterans who were exposed to contaminated water at Camp Lejeune are now eligible for VA care and benefits if they have been diagnosed with any of 8 diseases: adult leukemia, aplastic anemia and other myelodysplastic syndromes, bladder cancer, kidney cancer, liver cancer, multiple myeloma, non-Hodgkin lymphoma, and Parkinson disease. The presumption of service connection regulations went into effect March 14.

The newly effective rule complements the health care already provided for 15 illnesses or conditions as part of the Honoring America’s Veterans and Caring for Camp Lejeune Families Act of 2012. The Camp Lejeune Act requires the VA to provide health care to veterans who served at Camp Lejeune and to reimburse family members or pay providers for medical expenses for those who lived there for ≥ 30 days between August 1, 1953, and December 31, 1987.

The act and new rule relate to 2 on-base water wells that were contaminated with trichloroethylene, perchloroethylene, benzene, vinyl chloride, and other compounds. The wells were shut down in 1985.

The presumption of service connection applies to active-duty, reserve, and National Guard members. The presumption also includes all of Camp Lejeune, Marine Corps Air Station New River, as well as satellite camps and housing areas.

Micrograph showing DLBCL

WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.

The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).

Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.

There were 2 deaths related to axicabtagene ciloleucel.

Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).

ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.

Patients and treatment

The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.

Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.

Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.

Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.

For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m²) and fludarabine (30 mg/m²) for 3 days.

Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 10⁶ CAR T cells/kg.

Efficacy

The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.

The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.

Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.

At a median follow-up of 8.7 months, the median overall survival has not been reached.

Safety

The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.

“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.

There were 3 deaths throughout the course of the trial that were not a result of disease progression.

Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.

The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.

Micrograph showing DLBCL

WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.

The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).

Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.

There were 2 deaths related to axicabtagene ciloleucel.

Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).

ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.

Patients and treatment

The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.

Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.

Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.

Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.

For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m²) and fludarabine (30 mg/m²) for 3 days.

Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 10⁶ CAR T cells/kg.

Efficacy

The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.

The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.

Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.

At a median follow-up of 8.7 months, the median overall survival has not been reached.

Safety

The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.

“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.

There were 3 deaths throughout the course of the trial that were not a result of disease progression.

Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.

The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.

Micrograph showing DLBCL

WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.

The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).

Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.

There were 2 deaths related to axicabtagene ciloleucel.

Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).

ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.

Patients and treatment

The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.

Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.

Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.

Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.

For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m²) and fludarabine (30 mg/m²) for 3 days.

Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 10⁶ CAR T cells/kg.

Efficacy

The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.

The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.

Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.

At a median follow-up of 8.7 months, the median overall survival has not been reached.

Safety

The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.

“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.

There were 3 deaths throughout the course of the trial that were not a result of disease progression.

Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.

The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.

Red blood cells

Researchers say they have developed a new system for studying the resilience of red blood cells (RBCs).

The team’s microfluidic system allowed them to look at how RBCs spring back into shape after deforming to pass through a narrow channel.

The researchers believe their findings could aid the diagnosis and treatment of blood-related diseases such as septic shock and malaria.

Hiroaki Ito, PhD, of Osaka University in Suita, Japan, and his colleagues detailed these findings in Scientific Reports.

To study RBCs, the researchers built a “catch-load-launch” microfluidic platform.

The setup included a microchannel in which a single RBC could be held in place for any desired length of time. The RBC was ultimately launched into a wider section using a robotic pump, which simulates the transition from a capillary into a larger vessel.

“The cell was precisely localized in the microchannel by the combination of pressure control and real-time visual feedback,” explained study author Makoto Kaneko, of Osaka University.

“This let us ‘catch’ an erythrocyte in front of the constriction, ‘load’ it inside for a desired time, and quickly ‘launch’ it from the constriction to monitor the shape recovery over time.”

The researchers found that, as the time the RBC was held in the constricted region was increased—from 5 seconds all the way to 5 minutes—the time it took the cell to recover its normal shape also increased.

For very short constriction times, the cells bounced back within 1/10 of a second. But it took approximately 10 seconds for cells to recover if they were held in the narrow segment longer than about 3 minutes.

The researchers also used their “catch-load-launch” system to study septic shock. This condition can occur when bacteria invade the bloodstream and release endotoxins.

Patients with septic shock may suffer from reduced circulation inside the narrow blood vessels as RBCs become too stiff. The same problem can be caused by the malaria parasite Plasmodium falciparum.

The researchers exposed RBCs to endotoxin from the bacteria Salmonella minnesota and found the RBCs became stiffer and less resilient.

“There is a great deal of evidence that relates certain diseases, including sepsis and malaria, to a decrease in the deformability of red blood cells,” Dr Ito said.

“Such a stiffening can lead to a disturbance in microcirculation, and our ‘catch-load-launch’ platform has the potential to be applied to the mechanical diagnosis of these diseased blood cells.”

Red blood cells

Researchers say they have developed a new system for studying the resilience of red blood cells (RBCs).

The team’s microfluidic system allowed them to look at how RBCs spring back into shape after deforming to pass through a narrow channel.

The researchers believe their findings could aid the diagnosis and treatment of blood-related diseases such as septic shock and malaria.

Hiroaki Ito, PhD, of Osaka University in Suita, Japan, and his colleagues detailed these findings in Scientific Reports.

To study RBCs, the researchers built a “catch-load-launch” microfluidic platform.

The setup included a microchannel in which a single RBC could be held in place for any desired length of time. The RBC was ultimately launched into a wider section using a robotic pump, which simulates the transition from a capillary into a larger vessel.

“The cell was precisely localized in the microchannel by the combination of pressure control and real-time visual feedback,” explained study author Makoto Kaneko, of Osaka University.

“This let us ‘catch’ an erythrocyte in front of the constriction, ‘load’ it inside for a desired time, and quickly ‘launch’ it from the constriction to monitor the shape recovery over time.”

The researchers found that, as the time the RBC was held in the constricted region was increased—from 5 seconds all the way to 5 minutes—the time it took the cell to recover its normal shape also increased.

For very short constriction times, the cells bounced back within 1/10 of a second. But it took approximately 10 seconds for cells to recover if they were held in the narrow segment longer than about 3 minutes.

The researchers also used their “catch-load-launch” system to study septic shock. This condition can occur when bacteria invade the bloodstream and release endotoxins.

Patients with septic shock may suffer from reduced circulation inside the narrow blood vessels as RBCs become too stiff. The same problem can be caused by the malaria parasite Plasmodium falciparum.

The researchers exposed RBCs to endotoxin from the bacteria Salmonella minnesota and found the RBCs became stiffer and less resilient.

“There is a great deal of evidence that relates certain diseases, including sepsis and malaria, to a decrease in the deformability of red blood cells,” Dr Ito said.

“Such a stiffening can lead to a disturbance in microcirculation, and our ‘catch-load-launch’ platform has the potential to be applied to the mechanical diagnosis of these diseased blood cells.”

Red blood cells

Researchers say they have developed a new system for studying the resilience of red blood cells (RBCs).

The team’s microfluidic system allowed them to look at how RBCs spring back into shape after deforming to pass through a narrow channel.

The researchers believe their findings could aid the diagnosis and treatment of blood-related diseases such as septic shock and malaria.

Hiroaki Ito, PhD, of Osaka University in Suita, Japan, and his colleagues detailed these findings in Scientific Reports.

To study RBCs, the researchers built a “catch-load-launch” microfluidic platform.

The setup included a microchannel in which a single RBC could be held in place for any desired length of time. The RBC was ultimately launched into a wider section using a robotic pump, which simulates the transition from a capillary into a larger vessel.

“The cell was precisely localized in the microchannel by the combination of pressure control and real-time visual feedback,” explained study author Makoto Kaneko, of Osaka University.

“This let us ‘catch’ an erythrocyte in front of the constriction, ‘load’ it inside for a desired time, and quickly ‘launch’ it from the constriction to monitor the shape recovery over time.”

The researchers found that, as the time the RBC was held in the constricted region was increased—from 5 seconds all the way to 5 minutes—the time it took the cell to recover its normal shape also increased.

For very short constriction times, the cells bounced back within 1/10 of a second. But it took approximately 10 seconds for cells to recover if they were held in the narrow segment longer than about 3 minutes.

The researchers also used their “catch-load-launch” system to study septic shock. This condition can occur when bacteria invade the bloodstream and release endotoxins.

Patients with septic shock may suffer from reduced circulation inside the narrow blood vessels as RBCs become too stiff. The same problem can be caused by the malaria parasite Plasmodium falciparum.

The researchers exposed RBCs to endotoxin from the bacteria Salmonella minnesota and found the RBCs became stiffer and less resilient.

“There is a great deal of evidence that relates certain diseases, including sepsis and malaria, to a decrease in the deformability of red blood cells,” Dr Ito said.

“Such a stiffening can lead to a disturbance in microcirculation, and our ‘catch-load-launch’ platform has the potential to be applied to the mechanical diagnosis of these diseased blood cells.”

Micrograph showing CLL

WASHINGTON, DC—Preclinical research suggests a second-generation BTK inhibitor may overcome the acquired resistance observed with its predecessor in patients with chronic lymphocytic leukemia (CLL).

Investigators found the non-covalent BTK inhibitor SNS-062 was unaffected by the BTK C481S mutation, which confers resistance to the first-generation BTK inhibitor ibrutinib.

“[A] subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Amy Johnson, PhD, of The Ohio State University in Columbus.

“A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S.”

“In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”

Dr Johnson and her colleagues presented these findings at the AACR Annual Meeting 2017 (abstract 1207).

SNS-062 is being developed by Sunesis Pharmaceuticals, Inc., and company investigators were involved in this research. But the study was sponsored by The Ohio State University.

For this study, Dr Johnson and her colleagues tested SNS-062 in primary CLL cells and X-linked agammaglobulinemia human cell lines.

The investigators found that SNS-062 inhibited BTK, decreased the expression of B-cell activation markers, and reduced CLL cell viability in a dose-dependent manner. And these effects were comparable to those observed with ibrutinib.

SNS-062 and ibrutinib demonstrated comparable activity against wild-type BTK. However, ibrutinib and another BTK inhibitor, acalabrutinib, were hindered by the BTK C481S mutation, while SNS-062 was not.

The investigators said SNS-062 was 6 times more potent than ibrutinib against C481S BTK and more than 640 times more potent than acalabrutinib.

The team also noted that SNS-062 exhibited high specificity, affecting a limited number of kinases outside the TEC kinase family.

Finally, the investigators found that SNS-062 diminished stromal cell protection in CLL cells, suggesting the drug can hinder protection from the tumor microenvironment.

Micrograph showing CLL

WASHINGTON, DC—Preclinical research suggests a second-generation BTK inhibitor may overcome the acquired resistance observed with its predecessor in patients with chronic lymphocytic leukemia (CLL).

Investigators found the non-covalent BTK inhibitor SNS-062 was unaffected by the BTK C481S mutation, which confers resistance to the first-generation BTK inhibitor ibrutinib.

“[A] subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Amy Johnson, PhD, of The Ohio State University in Columbus.

“A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S.”

“In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”

Dr Johnson and her colleagues presented these findings at the AACR Annual Meeting 2017 (abstract 1207).

SNS-062 is being developed by Sunesis Pharmaceuticals, Inc., and company investigators were involved in this research. But the study was sponsored by The Ohio State University.

For this study, Dr Johnson and her colleagues tested SNS-062 in primary CLL cells and X-linked agammaglobulinemia human cell lines.

The investigators found that SNS-062 inhibited BTK, decreased the expression of B-cell activation markers, and reduced CLL cell viability in a dose-dependent manner. And these effects were comparable to those observed with ibrutinib.

SNS-062 and ibrutinib demonstrated comparable activity against wild-type BTK. However, ibrutinib and another BTK inhibitor, acalabrutinib, were hindered by the BTK C481S mutation, while SNS-062 was not.

The investigators said SNS-062 was 6 times more potent than ibrutinib against C481S BTK and more than 640 times more potent than acalabrutinib.

The team also noted that SNS-062 exhibited high specificity, affecting a limited number of kinases outside the TEC kinase family.

Finally, the investigators found that SNS-062 diminished stromal cell protection in CLL cells, suggesting the drug can hinder protection from the tumor microenvironment.

Micrograph showing CLL

WASHINGTON, DC—Preclinical research suggests a second-generation BTK inhibitor may overcome the acquired resistance observed with its predecessor in patients with chronic lymphocytic leukemia (CLL).

Investigators found the non-covalent BTK inhibitor SNS-062 was unaffected by the BTK C481S mutation, which confers resistance to the first-generation BTK inhibitor ibrutinib.

“[A] subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Amy Johnson, PhD, of The Ohio State University in Columbus.

“A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S.”

“In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”

Dr Johnson and her colleagues presented these findings at the AACR Annual Meeting 2017 (abstract 1207).

SNS-062 is being developed by Sunesis Pharmaceuticals, Inc., and company investigators were involved in this research. But the study was sponsored by The Ohio State University.

For this study, Dr Johnson and her colleagues tested SNS-062 in primary CLL cells and X-linked agammaglobulinemia human cell lines.

The investigators found that SNS-062 inhibited BTK, decreased the expression of B-cell activation markers, and reduced CLL cell viability in a dose-dependent manner. And these effects were comparable to those observed with ibrutinib.

SNS-062 and ibrutinib demonstrated comparable activity against wild-type BTK. However, ibrutinib and another BTK inhibitor, acalabrutinib, were hindered by the BTK C481S mutation, while SNS-062 was not.

The investigators said SNS-062 was 6 times more potent than ibrutinib against C481S BTK and more than 640 times more potent than acalabrutinib.

The team also noted that SNS-062 exhibited high specificity, affecting a limited number of kinases outside the TEC kinase family.

Finally, the investigators found that SNS-062 diminished stromal cell protection in CLL cells, suggesting the drug can hinder protection from the tumor microenvironment.