Recently, I had a trauma call at my scenic little hospital in Maine. “Bleeding leg wound, Dr, Crosslin. We’ve got pressure on it. Come soon.” During my jog across the parking lot to the ER, I drifted into my residency mantra and started reciting the ABCs of trauma care:

Airway, Breathing, CT scan.

Airway, Breathing, C-spine collar.

Airway, Breathing, Consult with ortho.



Okay, so it’s been a while. Four years doesn’t seem like a long time, but that little span serves up a lot of change. You settle into a routine in your isolated, bucolic New England coastal town, where most trauma is related to hauling up lobster crates and having Massachusetts drivers scare the moxie out of locals in the crosswalks, and you forget about the hundreds of Level 1 traumas you managed over 5 years in Boston. The drilled-down, rapid sequence of the primary and secondary surveys gets lost, if just for a moment. Your confident swagger is replaced with a measured, humble shuffle into Trauma Bay 1. Do I scan the leg now? Did I feel for pulses in the foot? Wait, where do the major vessels branch again?

Dr. Crosslin is a general surgeon practicing in Rockport, Maine.

Recently, I had a trauma call at my scenic little hospital in Maine. “Bleeding leg wound, Dr, Crosslin. We’ve got pressure on it. Come soon.” During my jog across the parking lot to the ER, I drifted into my residency mantra and started reciting the ABCs of trauma care:

Airway, Breathing, CT scan.

Airway, Breathing, C-spine collar.

Airway, Breathing, Consult with ortho.



Okay, so it’s been a while. Four years doesn’t seem like a long time, but that little span serves up a lot of change. You settle into a routine in your isolated, bucolic New England coastal town, where most trauma is related to hauling up lobster crates and having Massachusetts drivers scare the moxie out of locals in the crosswalks, and you forget about the hundreds of Level 1 traumas you managed over 5 years in Boston. The drilled-down, rapid sequence of the primary and secondary surveys gets lost, if just for a moment. Your confident swagger is replaced with a measured, humble shuffle into Trauma Bay 1. Do I scan the leg now? Did I feel for pulses in the foot? Wait, where do the major vessels branch again?

Dr. Crosslin is a general surgeon practicing in Rockport, Maine.

Recently, I had a trauma call at my scenic little hospital in Maine. “Bleeding leg wound, Dr, Crosslin. We’ve got pressure on it. Come soon.” During my jog across the parking lot to the ER, I drifted into my residency mantra and started reciting the ABCs of trauma care:

Airway, Breathing, CT scan.

Airway, Breathing, C-spine collar.

Airway, Breathing, Consult with ortho.



Okay, so it’s been a while. Four years doesn’t seem like a long time, but that little span serves up a lot of change. You settle into a routine in your isolated, bucolic New England coastal town, where most trauma is related to hauling up lobster crates and having Massachusetts drivers scare the moxie out of locals in the crosswalks, and you forget about the hundreds of Level 1 traumas you managed over 5 years in Boston. The drilled-down, rapid sequence of the primary and secondary surveys gets lost, if just for a moment. Your confident swagger is replaced with a measured, humble shuffle into Trauma Bay 1. Do I scan the leg now? Did I feel for pulses in the foot? Wait, where do the major vessels branch again?

Dr. Crosslin is a general surgeon practicing in Rockport, Maine.

CHICAGO – The 10-year incidence rates for both squamous cell carcinoma and basal cell carcinoma arising after hematopoietic cell transplantation are impressively high at 17%-plus for each, but the malignancies occur on two very different timelines, according to Jeffrey F. Scott, MD, a fellow in micrographic surgery and dermatologic oncology at Case Western Reserve University in Cleveland.

Most of the squamous cell carcinomas (SCCs) in a large multicenter retrospective study developed within the first 5 years following hematopoietic cell transplantation (HCT), while the majority of the basal cell carcinomas (BCCs) occurred after that point, Dr. Scott reported at the annual meeting of the American College of Mohs Surgery.

He presented the results of the study, which included 876 HCT recipients followed for a mean of 6.1 years. The study objective was to pin down the risk factors for skin cancer after HCT, especially the patient-specific ones. This has become a pressing issue because the use of HCT is steadily growing, and the 5-year survival rate now exceeds 50%.

The transplant-specific risk factors have previously been fairly well described by others. They include the donor source, type of disease, the conditioning regimen, whether whole body irradiation was used, immunosuppression, graft versus host disease (GVHD), and others.

The patient-centric risk factors, in contrast, have not been well characterized. And it’s critical to thoroughly understand these risk factors in order to develop targeted prevention and surveillance strategies, Dr. Scott said.

“There remains a significant knowledge gap within our field. I would venture that the majority of this audience has treated a patient with skin cancer who has had a transplant,” he said. “Yet when a patient asks us, ‘Doc, what is my risk for skin cancer after my HCT?’ we’re really unable to give them an accurate and complete assessment of that risk. That’s because we’re missing the second major category of risk factors: the patient-specific risk factors.”

The reason for that, he added, is that the major population-based studies and national HCT registries are run by hematologists and oncologists, and they haven’t adequately captured the patient-specific skin cancer risk factors. But these are variables very familiar to dermatologists. They include skin phenotype, history of UV radiation exposure, and history of pre-HCT skin cancer.

Dr. Scott said the multicenter study he presented has two major advantages over prior studies: its large size and thorough followup. Nearly all 876 patients were followed by both an oncologist and a dermatologist at the same institution.

During followup, the HCT recipients collectively developed 63 SCCs, 55 BCCs, and 16 malignant melanomas. The 5- and 10-year incidence rates for SCC were 10.6% and 17.2%. For BCC, the 5- and 10-year rates were 5.7% and 17.6%. All 16 cases of melanoma occurred within 5 years after HCT.

In multivariate Cox proportional hazard analyses, photodamage documented on examination was independently associated with a 3.2-fold increased risk of post-HCT SCC and a 3.5-fold increased risk of BCC.

A pre-transplant history of BCC was associated with a 3.9-fold increased likelihood of developing a BCC afterwards. Similarly, a pre-HCT history of SCC conferred a 4.2-fold increased risk of post-transplant SCC and was also independently associated with a 6.6-fold increased risk of developing melanoma post-HCT.

Fitzpatrick skin types I and II were respectively associated with 9.3- and 7.2-fold increased risks of post-HCT nonmelanoma skin cancer, compared with skin types III-VI.

Acute GVHD wasn’t associated with an increased risk of nonmelanoma skin cancer after HCT. However, in an observation that hasn’t previously been reported by others, chronic GVHD with skin involvement was associated with a 2.7-fold increased likelihood of SCC post-HCT, Dr. Scott noted.

What’s next for Dr. Scott and his coinvestigators? “Our ultimate goal with this project is to develop an interactive risk assessment tool like the National Cancer Institute’s Breast Cancer Risk Assessment Tool that can be online and used by patients and providers to estimate their individualized risk of basal cell carcinoma, squamous cell carcinoma, and melanoma after HCT,” he said.

Dr. Scott reported having no financial conflicts related to the study.

[email protected]

CHICAGO – The 10-year incidence rates for both squamous cell carcinoma and basal cell carcinoma arising after hematopoietic cell transplantation are impressively high at 17%-plus for each, but the malignancies occur on two very different timelines, according to Jeffrey F. Scott, MD, a fellow in micrographic surgery and dermatologic oncology at Case Western Reserve University in Cleveland.

Most of the squamous cell carcinomas (SCCs) in a large multicenter retrospective study developed within the first 5 years following hematopoietic cell transplantation (HCT), while the majority of the basal cell carcinomas (BCCs) occurred after that point, Dr. Scott reported at the annual meeting of the American College of Mohs Surgery.

He presented the results of the study, which included 876 HCT recipients followed for a mean of 6.1 years. The study objective was to pin down the risk factors for skin cancer after HCT, especially the patient-specific ones. This has become a pressing issue because the use of HCT is steadily growing, and the 5-year survival rate now exceeds 50%.

The transplant-specific risk factors have previously been fairly well described by others. They include the donor source, type of disease, the conditioning regimen, whether whole body irradiation was used, immunosuppression, graft versus host disease (GVHD), and others.

The patient-centric risk factors, in contrast, have not been well characterized. And it’s critical to thoroughly understand these risk factors in order to develop targeted prevention and surveillance strategies, Dr. Scott said.

“There remains a significant knowledge gap within our field. I would venture that the majority of this audience has treated a patient with skin cancer who has had a transplant,” he said. “Yet when a patient asks us, ‘Doc, what is my risk for skin cancer after my HCT?’ we’re really unable to give them an accurate and complete assessment of that risk. That’s because we’re missing the second major category of risk factors: the patient-specific risk factors.”

The reason for that, he added, is that the major population-based studies and national HCT registries are run by hematologists and oncologists, and they haven’t adequately captured the patient-specific skin cancer risk factors. But these are variables very familiar to dermatologists. They include skin phenotype, history of UV radiation exposure, and history of pre-HCT skin cancer.

Dr. Scott said the multicenter study he presented has two major advantages over prior studies: its large size and thorough followup. Nearly all 876 patients were followed by both an oncologist and a dermatologist at the same institution.

During followup, the HCT recipients collectively developed 63 SCCs, 55 BCCs, and 16 malignant melanomas. The 5- and 10-year incidence rates for SCC were 10.6% and 17.2%. For BCC, the 5- and 10-year rates were 5.7% and 17.6%. All 16 cases of melanoma occurred within 5 years after HCT.

In multivariate Cox proportional hazard analyses, photodamage documented on examination was independently associated with a 3.2-fold increased risk of post-HCT SCC and a 3.5-fold increased risk of BCC.

A pre-transplant history of BCC was associated with a 3.9-fold increased likelihood of developing a BCC afterwards. Similarly, a pre-HCT history of SCC conferred a 4.2-fold increased risk of post-transplant SCC and was also independently associated with a 6.6-fold increased risk of developing melanoma post-HCT.

Fitzpatrick skin types I and II were respectively associated with 9.3- and 7.2-fold increased risks of post-HCT nonmelanoma skin cancer, compared with skin types III-VI.

Acute GVHD wasn’t associated with an increased risk of nonmelanoma skin cancer after HCT. However, in an observation that hasn’t previously been reported by others, chronic GVHD with skin involvement was associated with a 2.7-fold increased likelihood of SCC post-HCT, Dr. Scott noted.

What’s next for Dr. Scott and his coinvestigators? “Our ultimate goal with this project is to develop an interactive risk assessment tool like the National Cancer Institute’s Breast Cancer Risk Assessment Tool that can be online and used by patients and providers to estimate their individualized risk of basal cell carcinoma, squamous cell carcinoma, and melanoma after HCT,” he said.

Dr. Scott reported having no financial conflicts related to the study.

[email protected]

CHICAGO – The 10-year incidence rates for both squamous cell carcinoma and basal cell carcinoma arising after hematopoietic cell transplantation are impressively high at 17%-plus for each, but the malignancies occur on two very different timelines, according to Jeffrey F. Scott, MD, a fellow in micrographic surgery and dermatologic oncology at Case Western Reserve University in Cleveland.

Most of the squamous cell carcinomas (SCCs) in a large multicenter retrospective study developed within the first 5 years following hematopoietic cell transplantation (HCT), while the majority of the basal cell carcinomas (BCCs) occurred after that point, Dr. Scott reported at the annual meeting of the American College of Mohs Surgery.

He presented the results of the study, which included 876 HCT recipients followed for a mean of 6.1 years. The study objective was to pin down the risk factors for skin cancer after HCT, especially the patient-specific ones. This has become a pressing issue because the use of HCT is steadily growing, and the 5-year survival rate now exceeds 50%.

The transplant-specific risk factors have previously been fairly well described by others. They include the donor source, type of disease, the conditioning regimen, whether whole body irradiation was used, immunosuppression, graft versus host disease (GVHD), and others.

The patient-centric risk factors, in contrast, have not been well characterized. And it’s critical to thoroughly understand these risk factors in order to develop targeted prevention and surveillance strategies, Dr. Scott said.

“There remains a significant knowledge gap within our field. I would venture that the majority of this audience has treated a patient with skin cancer who has had a transplant,” he said. “Yet when a patient asks us, ‘Doc, what is my risk for skin cancer after my HCT?’ we’re really unable to give them an accurate and complete assessment of that risk. That’s because we’re missing the second major category of risk factors: the patient-specific risk factors.”

The reason for that, he added, is that the major population-based studies and national HCT registries are run by hematologists and oncologists, and they haven’t adequately captured the patient-specific skin cancer risk factors. But these are variables very familiar to dermatologists. They include skin phenotype, history of UV radiation exposure, and history of pre-HCT skin cancer.

Dr. Scott said the multicenter study he presented has two major advantages over prior studies: its large size and thorough followup. Nearly all 876 patients were followed by both an oncologist and a dermatologist at the same institution.

During followup, the HCT recipients collectively developed 63 SCCs, 55 BCCs, and 16 malignant melanomas. The 5- and 10-year incidence rates for SCC were 10.6% and 17.2%. For BCC, the 5- and 10-year rates were 5.7% and 17.6%. All 16 cases of melanoma occurred within 5 years after HCT.

In multivariate Cox proportional hazard analyses, photodamage documented on examination was independently associated with a 3.2-fold increased risk of post-HCT SCC and a 3.5-fold increased risk of BCC.

A pre-transplant history of BCC was associated with a 3.9-fold increased likelihood of developing a BCC afterwards. Similarly, a pre-HCT history of SCC conferred a 4.2-fold increased risk of post-transplant SCC and was also independently associated with a 6.6-fold increased risk of developing melanoma post-HCT.

Fitzpatrick skin types I and II were respectively associated with 9.3- and 7.2-fold increased risks of post-HCT nonmelanoma skin cancer, compared with skin types III-VI.

Acute GVHD wasn’t associated with an increased risk of nonmelanoma skin cancer after HCT. However, in an observation that hasn’t previously been reported by others, chronic GVHD with skin involvement was associated with a 2.7-fold increased likelihood of SCC post-HCT, Dr. Scott noted.

What’s next for Dr. Scott and his coinvestigators? “Our ultimate goal with this project is to develop an interactive risk assessment tool like the National Cancer Institute’s Breast Cancer Risk Assessment Tool that can be online and used by patients and providers to estimate their individualized risk of basal cell carcinoma, squamous cell carcinoma, and melanoma after HCT,” he said.

Dr. Scott reported having no financial conflicts related to the study.

[email protected]

The Food and Drug Administration is generally achieving the balance between ensuring safety and providing access to investigational drugs through compassionate use programs, according to results from a new analysis that found that most of these drugs are available within 6 months of an application to the FDA.

But that balance may be threatened by the recently enacted Right to Try Act, Jeremy Puthumana, of Yale University, New Haven, Conn., and his colleagues reported in an article published on JAMA Network Open. They said the new law encourages sponsors to make investigational drugs available earlier in the clinical development period, potentially jeopardizing safety.

“These findings suggest the FDA and the pharmaceutical industry have established a balance between investigational new drug access and protection of patients from therapies without established safety, which may be compromised by policy makers seeking to speed access to investigational medicines through the Right to Try Act by removing the requirements for FDA oversight and approval of expanded access requests,” the researchers wrote.

The cross-sectional study examined all expanded access programs registered with ClinicalTrials.gov through Aug. 1, 2017. Of 92 expanded access programs for investigational drugs, 69.6% were initiated within 6 months following (43.5%) or preceding (26.1%) submission of a new drug application. Ninety of the 92 drugs ultimately went on to receive FDA approval.

[email protected]

SOURCE: Puthumana J et al. JAMA Network Open. 2018 Jun 15. doi:10.1001/jamanetworkopen.2018.0283.

The Food and Drug Administration is generally achieving the balance between ensuring safety and providing access to investigational drugs through compassionate use programs, according to results from a new analysis that found that most of these drugs are available within 6 months of an application to the FDA.

But that balance may be threatened by the recently enacted Right to Try Act, Jeremy Puthumana, of Yale University, New Haven, Conn., and his colleagues reported in an article published on JAMA Network Open. They said the new law encourages sponsors to make investigational drugs available earlier in the clinical development period, potentially jeopardizing safety.

“These findings suggest the FDA and the pharmaceutical industry have established a balance between investigational new drug access and protection of patients from therapies without established safety, which may be compromised by policy makers seeking to speed access to investigational medicines through the Right to Try Act by removing the requirements for FDA oversight and approval of expanded access requests,” the researchers wrote.

The cross-sectional study examined all expanded access programs registered with ClinicalTrials.gov through Aug. 1, 2017. Of 92 expanded access programs for investigational drugs, 69.6% were initiated within 6 months following (43.5%) or preceding (26.1%) submission of a new drug application. Ninety of the 92 drugs ultimately went on to receive FDA approval.

[email protected]

SOURCE: Puthumana J et al. JAMA Network Open. 2018 Jun 15. doi:10.1001/jamanetworkopen.2018.0283.

The Food and Drug Administration is generally achieving the balance between ensuring safety and providing access to investigational drugs through compassionate use programs, according to results from a new analysis that found that most of these drugs are available within 6 months of an application to the FDA.

But that balance may be threatened by the recently enacted Right to Try Act, Jeremy Puthumana, of Yale University, New Haven, Conn., and his colleagues reported in an article published on JAMA Network Open. They said the new law encourages sponsors to make investigational drugs available earlier in the clinical development period, potentially jeopardizing safety.

“These findings suggest the FDA and the pharmaceutical industry have established a balance between investigational new drug access and protection of patients from therapies without established safety, which may be compromised by policy makers seeking to speed access to investigational medicines through the Right to Try Act by removing the requirements for FDA oversight and approval of expanded access requests,” the researchers wrote.

The cross-sectional study examined all expanded access programs registered with ClinicalTrials.gov through Aug. 1, 2017. Of 92 expanded access programs for investigational drugs, 69.6% were initiated within 6 months following (43.5%) or preceding (26.1%) submission of a new drug application. Ninety of the 92 drugs ultimately went on to receive FDA approval.

[email protected]

SOURCE: Puthumana J et al. JAMA Network Open. 2018 Jun 15. doi:10.1001/jamanetworkopen.2018.0283.

AMSTERDAM – Low blood levels of vitamin D were linked with a roughly doubled risk for deep vein thrombosis in a review of nearly 1,400 patients with systemic lupus erythematosus at one U.S. center.

Based on these findings, patients with systemic lupus erythematosus (SLE) should have their blood vitamin D monitored regularly, and if it’s less than 40 ng/mL – the level that was linked with this thrombotic risk – they should receive a vitamin D supplement, Michelle A. Petri, MD, said while presenting a poster at the European Congress of Rheumatology.

She recommended supplementation that provides 50,000 IU of vitamin D weekly, a treatment that appears safe to add to two other routine treatments she recommends for SLE patients – aspirin and hydroxychloroquine.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):388, Abstract THU0341.

AMSTERDAM – Low blood levels of vitamin D were linked with a roughly doubled risk for deep vein thrombosis in a review of nearly 1,400 patients with systemic lupus erythematosus at one U.S. center.

Based on these findings, patients with systemic lupus erythematosus (SLE) should have their blood vitamin D monitored regularly, and if it’s less than 40 ng/mL – the level that was linked with this thrombotic risk – they should receive a vitamin D supplement, Michelle A. Petri, MD, said while presenting a poster at the European Congress of Rheumatology.

She recommended supplementation that provides 50,000 IU of vitamin D weekly, a treatment that appears safe to add to two other routine treatments she recommends for SLE patients – aspirin and hydroxychloroquine.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):388, Abstract THU0341.

AMSTERDAM – Low blood levels of vitamin D were linked with a roughly doubled risk for deep vein thrombosis in a review of nearly 1,400 patients with systemic lupus erythematosus at one U.S. center.

Based on these findings, patients with systemic lupus erythematosus (SLE) should have their blood vitamin D monitored regularly, and if it’s less than 40 ng/mL – the level that was linked with this thrombotic risk – they should receive a vitamin D supplement, Michelle A. Petri, MD, said while presenting a poster at the European Congress of Rheumatology.

She recommended supplementation that provides 50,000 IU of vitamin D weekly, a treatment that appears safe to add to two other routine treatments she recommends for SLE patients – aspirin and hydroxychloroquine.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):388, Abstract THU0341.

STOCKHOLM, SWEDEN – A novel chimeric antigen receptor T-cell construct directed against CD22 was able to rescue children with relapsed or refractory B-cell acute lymphoblastic leukemia for whom CD19-directed CAR T therapy had failed, investigators from China reported.

Thirty days after CAR T cell infusion, 12 of 15 children (80%) treated with the unnamed CD22 CAR T product had a complete response (CR) and one (6.7%) had a partial response (PR), for an overall response rate (ORR) of 86.7%, said Jing Pan, MD, from the Beijing Boren Hospital in China.

Surprisingly for a therapy of its type, the CD22 CAR T was well tolerated, with only mild cases of the cytokine release syndrome (CRS), and it could be delivered safely in children with relapsed disease after hematopoietic cell transplants (HCT), she reported in a briefing and in an oral abstract session at the annual congress of the European Hematology Association.

“CD22 CAR T immunotherapy brings hope for patients with refractory or relapsed B-ALL who failed on CD19 CAR T immunotherapy, and we think it’s quite safe. No children died and no children had severe side effects during the study, even in post-HCT patients,” Dr. Pan said.

She noted that in a previous clinical trial by her group, some patients experienced relapses and were resistant to retreatment with CD19-directed CAR T therapy due to mutations or loss of the CD19 antigen (Leukemia. 2017 Dec;31[12]:2587-93).

Since CD22 is highly expressed on leukemic cells in children with B-ALL, the investigators decided to evaluate the safety and efficacy of a CD22 CAR T as a rescue strategy. They enrolled 15 patients who either experienced relapse or did not have a response to CD19 CAR T immunotherapy. The CAR T construct they used contains an anti-CD22 single-chain variable fragment derived from a humanized CD22 antibody.

Patient conditioning with fludarabine and cyclophosphamide was performed simultaneously with CAR T transfection and expansion. After about 7 days, the expanded and transformed CAR T cells were infused at a dose of 8.2 x 10⁵/kg in patients who had not undergone HCT, and 0.9 x 10⁵ in patients who had received a transplant.

The patients ranged from 2 to 18 years old (median 8 years), had a median disease course of 21 months (range 5-84 months), and had a median of 42% bone marrow blasts (range 5%-95.5%).

Four of the 15 patients had relapses following allogeneic HCT, and the remaining 11 had relapses following chemotherapy. Two of the patients were found to be minimal residual disease (MRD)-positive by flow cytometry. Two patients had extramedullary disease only at relapse.

Ten of 11 patients who had experienced a hematologic relapse had either a CR or CR with incomplete recovery of counts (CRi), and of these 10 patients, nine were determined on follow-up to be MRD-negative by flow cytometry.

One of the two patients with extramedullary disease had a CR, and the other had a partial response.

Although two patients had no response to CD22 CAR T therapy, expression of the antigen was strong on leukemia cells from these patients, Dr. Pan said.

All patients experienced CRS, but none had greater than grade 2, Dr. Pan said, although she did not provide give specific numbers. Two patients had grade 1 neurotoxicity, two patients had grade 2 hypoxemia, and one patient had grade 2 liver enzyme elevation.

At a median follow-up of 108 days, six patients had been bridged to allogeneic HCT, and eleven of 12 patients who had a CR or CRi at 30 days had no evidence of disease progression. The remaining patient with an initial CR or CRi had a relapse at day 50. The 6-month progression-free survival rate was 91.7%.

Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, commented that given the high leukemia burden of the patients and the apparent efficacy of the therapy, one would expect to see higher grades of CRS, and asked Dr. Pan whether she could account for the CRS findings in her study, compared with those of trials for CD19-directed CAR T therapy.

It may have to do with differences in density of CD22 expression, compared with CD19 expression on leukemia cells, or on differences in the antibody used to target the cells, Dr. Pan said.

SOURCE: Pan J et al. EHA Congress, Abstract S832.

STOCKHOLM, SWEDEN – A novel chimeric antigen receptor T-cell construct directed against CD22 was able to rescue children with relapsed or refractory B-cell acute lymphoblastic leukemia for whom CD19-directed CAR T therapy had failed, investigators from China reported.

Thirty days after CAR T cell infusion, 12 of 15 children (80%) treated with the unnamed CD22 CAR T product had a complete response (CR) and one (6.7%) had a partial response (PR), for an overall response rate (ORR) of 86.7%, said Jing Pan, MD, from the Beijing Boren Hospital in China.

Surprisingly for a therapy of its type, the CD22 CAR T was well tolerated, with only mild cases of the cytokine release syndrome (CRS), and it could be delivered safely in children with relapsed disease after hematopoietic cell transplants (HCT), she reported in a briefing and in an oral abstract session at the annual congress of the European Hematology Association.

“CD22 CAR T immunotherapy brings hope for patients with refractory or relapsed B-ALL who failed on CD19 CAR T immunotherapy, and we think it’s quite safe. No children died and no children had severe side effects during the study, even in post-HCT patients,” Dr. Pan said.

She noted that in a previous clinical trial by her group, some patients experienced relapses and were resistant to retreatment with CD19-directed CAR T therapy due to mutations or loss of the CD19 antigen (Leukemia. 2017 Dec;31[12]:2587-93).

Since CD22 is highly expressed on leukemic cells in children with B-ALL, the investigators decided to evaluate the safety and efficacy of a CD22 CAR T as a rescue strategy. They enrolled 15 patients who either experienced relapse or did not have a response to CD19 CAR T immunotherapy. The CAR T construct they used contains an anti-CD22 single-chain variable fragment derived from a humanized CD22 antibody.

Patient conditioning with fludarabine and cyclophosphamide was performed simultaneously with CAR T transfection and expansion. After about 7 days, the expanded and transformed CAR T cells were infused at a dose of 8.2 x 10⁵/kg in patients who had not undergone HCT, and 0.9 x 10⁵ in patients who had received a transplant.

The patients ranged from 2 to 18 years old (median 8 years), had a median disease course of 21 months (range 5-84 months), and had a median of 42% bone marrow blasts (range 5%-95.5%).

Four of the 15 patients had relapses following allogeneic HCT, and the remaining 11 had relapses following chemotherapy. Two of the patients were found to be minimal residual disease (MRD)-positive by flow cytometry. Two patients had extramedullary disease only at relapse.

Ten of 11 patients who had experienced a hematologic relapse had either a CR or CR with incomplete recovery of counts (CRi), and of these 10 patients, nine were determined on follow-up to be MRD-negative by flow cytometry.

One of the two patients with extramedullary disease had a CR, and the other had a partial response.

Although two patients had no response to CD22 CAR T therapy, expression of the antigen was strong on leukemia cells from these patients, Dr. Pan said.

All patients experienced CRS, but none had greater than grade 2, Dr. Pan said, although she did not provide give specific numbers. Two patients had grade 1 neurotoxicity, two patients had grade 2 hypoxemia, and one patient had grade 2 liver enzyme elevation.

At a median follow-up of 108 days, six patients had been bridged to allogeneic HCT, and eleven of 12 patients who had a CR or CRi at 30 days had no evidence of disease progression. The remaining patient with an initial CR or CRi had a relapse at day 50. The 6-month progression-free survival rate was 91.7%.

Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, commented that given the high leukemia burden of the patients and the apparent efficacy of the therapy, one would expect to see higher grades of CRS, and asked Dr. Pan whether she could account for the CRS findings in her study, compared with those of trials for CD19-directed CAR T therapy.

It may have to do with differences in density of CD22 expression, compared with CD19 expression on leukemia cells, or on differences in the antibody used to target the cells, Dr. Pan said.

SOURCE: Pan J et al. EHA Congress, Abstract S832.

STOCKHOLM, SWEDEN – A novel chimeric antigen receptor T-cell construct directed against CD22 was able to rescue children with relapsed or refractory B-cell acute lymphoblastic leukemia for whom CD19-directed CAR T therapy had failed, investigators from China reported.

Thirty days after CAR T cell infusion, 12 of 15 children (80%) treated with the unnamed CD22 CAR T product had a complete response (CR) and one (6.7%) had a partial response (PR), for an overall response rate (ORR) of 86.7%, said Jing Pan, MD, from the Beijing Boren Hospital in China.

Surprisingly for a therapy of its type, the CD22 CAR T was well tolerated, with only mild cases of the cytokine release syndrome (CRS), and it could be delivered safely in children with relapsed disease after hematopoietic cell transplants (HCT), she reported in a briefing and in an oral abstract session at the annual congress of the European Hematology Association.

“CD22 CAR T immunotherapy brings hope for patients with refractory or relapsed B-ALL who failed on CD19 CAR T immunotherapy, and we think it’s quite safe. No children died and no children had severe side effects during the study, even in post-HCT patients,” Dr. Pan said.

She noted that in a previous clinical trial by her group, some patients experienced relapses and were resistant to retreatment with CD19-directed CAR T therapy due to mutations or loss of the CD19 antigen (Leukemia. 2017 Dec;31[12]:2587-93).

Since CD22 is highly expressed on leukemic cells in children with B-ALL, the investigators decided to evaluate the safety and efficacy of a CD22 CAR T as a rescue strategy. They enrolled 15 patients who either experienced relapse or did not have a response to CD19 CAR T immunotherapy. The CAR T construct they used contains an anti-CD22 single-chain variable fragment derived from a humanized CD22 antibody.

Patient conditioning with fludarabine and cyclophosphamide was performed simultaneously with CAR T transfection and expansion. After about 7 days, the expanded and transformed CAR T cells were infused at a dose of 8.2 x 10⁵/kg in patients who had not undergone HCT, and 0.9 x 10⁵ in patients who had received a transplant.

The patients ranged from 2 to 18 years old (median 8 years), had a median disease course of 21 months (range 5-84 months), and had a median of 42% bone marrow blasts (range 5%-95.5%).

Four of the 15 patients had relapses following allogeneic HCT, and the remaining 11 had relapses following chemotherapy. Two of the patients were found to be minimal residual disease (MRD)-positive by flow cytometry. Two patients had extramedullary disease only at relapse.

Ten of 11 patients who had experienced a hematologic relapse had either a CR or CR with incomplete recovery of counts (CRi), and of these 10 patients, nine were determined on follow-up to be MRD-negative by flow cytometry.

One of the two patients with extramedullary disease had a CR, and the other had a partial response.

Although two patients had no response to CD22 CAR T therapy, expression of the antigen was strong on leukemia cells from these patients, Dr. Pan said.

All patients experienced CRS, but none had greater than grade 2, Dr. Pan said, although she did not provide give specific numbers. Two patients had grade 1 neurotoxicity, two patients had grade 2 hypoxemia, and one patient had grade 2 liver enzyme elevation.

At a median follow-up of 108 days, six patients had been bridged to allogeneic HCT, and eleven of 12 patients who had a CR or CRi at 30 days had no evidence of disease progression. The remaining patient with an initial CR or CRi had a relapse at day 50. The 6-month progression-free survival rate was 91.7%.

Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, commented that given the high leukemia burden of the patients and the apparent efficacy of the therapy, one would expect to see higher grades of CRS, and asked Dr. Pan whether she could account for the CRS findings in her study, compared with those of trials for CD19-directed CAR T therapy.

It may have to do with differences in density of CD22 expression, compared with CD19 expression on leukemia cells, or on differences in the antibody used to target the cells, Dr. Pan said.

SOURCE: Pan J et al. EHA Congress, Abstract S832.

STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.

Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.

More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.

“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.

However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.

SOURCE: Sehn LH et al. EHA Congress, Abstract S802.

STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.

Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.

More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.

“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.

However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.

SOURCE: Sehn LH et al. EHA Congress, Abstract S802.

STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.

Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a phase 2 trial, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.

More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.

“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.

However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.

SOURCE: Sehn LH et al. EHA Congress, Abstract S802.

Vascular loops are rare congenital optic nerve anomalies that originate from the arterial or venous circulation; 90% arise from the arterial circulation.¹ Vascular loops are usually asymptomatic unless an arterial or venous occlusion, hyphema, and vitreous or preretinal hemorrhage should arise.^1-8 This article describes a patient who presented with a vitreous hemorrhage secondary to a vascular loop.

Case Presentation

A 67-year-old white male presented to the eye clinic at the Providence VA Medical Center in Rhode Island after experiencing floaters and “snowflakes” in the left eye for 2 days. The patient reported having no photopsias, loss of vision, preceding eye/head trauma, or Valsalva maneuver. His medical history was significant for well-controlled type 2 diabetes mellitus (known duration of 5 years), hypertension, hyperlipidemia, coronary artery disease, and anemia. His medications included aspirin 81 mg, furosemide, clonidine, labetalol, valsartan, glipizide, and lantus injections.

The patient’s ocular history was significant for cataracts in both eyes. On examination, best-corrected visual acuity was 20/20 in each eye with intraocular pressures of 15 mm Hg in the right eye and 14 mm Hg in the left eye. Anterior segment examination was notable for 1+ nuclear sclerotic cataracts in both eyes with red blood cells visible in the anterior chamber in the left eye. 

No PVD, retinal break, or detachment was present in the left eye with scleral depression. No background diabetic retinopathy was present in either eye. 

The patient was diagnosed with a vitreous hemorrhage associated with a vascular loop in the left eye. 

Discussion

Salient features of this case include the prominent vascular loop at the disc extending anteriorly into the vitreous and an absence of features suggestive of one of the more common etiologies of vitreous hemorrhage, such as PVD, retinal tear/detachment, proliferative diabetic retinopathy (PDR), or retinal vein occlusion.

The incidence of venous loops is 1 in 9,000 with no associated systemic conditions.^2,3 Typically unilateral, vascular loops arise at the optic disc from the central retinal artery or vein.^1-4 An arterial loop is a separate entity from a hyaloid artery.² The authors were unable to definitively determine whether the loop in this patient was arterial or venous in origin due to blockage from the associated retinal hemorrhage on FA.

Valsalva maneuver, vitreous traction, trauma, and loop torsion in patients with vascular loops can lead to amaurosis fugax, PVD, and hemorrhagic complications, such as hyphema and vitreous and retinal hemorrhages.^1,3,6-8 In addition, retinal ischemia and thrombosis from the vascular loops can lead to retinal artery or vein occlusions.^1-8 Vitreous and retinal hemorrhages, such as in this patient, are often observed with complete resolution and visual acuity returning to baseline.^4,5 For recurrent or nonresolving vitreous hemorrhages, a vitrectomy can be performed.^3,6

Conclusion

Patients with vascular loops should be educated to seek eye care if experiencing new onset floaters or visual loss.

Vascular loops are rare congenital optic nerve anomalies that originate from the arterial or venous circulation; 90% arise from the arterial circulation.¹ Vascular loops are usually asymptomatic unless an arterial or venous occlusion, hyphema, and vitreous or preretinal hemorrhage should arise.^1-8 This article describes a patient who presented with a vitreous hemorrhage secondary to a vascular loop.

Case Presentation

A 67-year-old white male presented to the eye clinic at the Providence VA Medical Center in Rhode Island after experiencing floaters and “snowflakes” in the left eye for 2 days. The patient reported having no photopsias, loss of vision, preceding eye/head trauma, or Valsalva maneuver. His medical history was significant for well-controlled type 2 diabetes mellitus (known duration of 5 years), hypertension, hyperlipidemia, coronary artery disease, and anemia. His medications included aspirin 81 mg, furosemide, clonidine, labetalol, valsartan, glipizide, and lantus injections.

The patient’s ocular history was significant for cataracts in both eyes. On examination, best-corrected visual acuity was 20/20 in each eye with intraocular pressures of 15 mm Hg in the right eye and 14 mm Hg in the left eye. Anterior segment examination was notable for 1+ nuclear sclerotic cataracts in both eyes with red blood cells visible in the anterior chamber in the left eye. 

No PVD, retinal break, or detachment was present in the left eye with scleral depression. No background diabetic retinopathy was present in either eye. 

The patient was diagnosed with a vitreous hemorrhage associated with a vascular loop in the left eye. 

Discussion

Salient features of this case include the prominent vascular loop at the disc extending anteriorly into the vitreous and an absence of features suggestive of one of the more common etiologies of vitreous hemorrhage, such as PVD, retinal tear/detachment, proliferative diabetic retinopathy (PDR), or retinal vein occlusion.

The incidence of venous loops is 1 in 9,000 with no associated systemic conditions.^2,3 Typically unilateral, vascular loops arise at the optic disc from the central retinal artery or vein.^1-4 An arterial loop is a separate entity from a hyaloid artery.² The authors were unable to definitively determine whether the loop in this patient was arterial or venous in origin due to blockage from the associated retinal hemorrhage on FA.

Valsalva maneuver, vitreous traction, trauma, and loop torsion in patients with vascular loops can lead to amaurosis fugax, PVD, and hemorrhagic complications, such as hyphema and vitreous and retinal hemorrhages.^1,3,6-8 In addition, retinal ischemia and thrombosis from the vascular loops can lead to retinal artery or vein occlusions.^1-8 Vitreous and retinal hemorrhages, such as in this patient, are often observed with complete resolution and visual acuity returning to baseline.^4,5 For recurrent or nonresolving vitreous hemorrhages, a vitrectomy can be performed.^3,6

Conclusion

Patients with vascular loops should be educated to seek eye care if experiencing new onset floaters or visual loss.

Vascular loops are rare congenital optic nerve anomalies that originate from the arterial or venous circulation; 90% arise from the arterial circulation.¹ Vascular loops are usually asymptomatic unless an arterial or venous occlusion, hyphema, and vitreous or preretinal hemorrhage should arise.^1-8 This article describes a patient who presented with a vitreous hemorrhage secondary to a vascular loop.

Case Presentation

A 67-year-old white male presented to the eye clinic at the Providence VA Medical Center in Rhode Island after experiencing floaters and “snowflakes” in the left eye for 2 days. The patient reported having no photopsias, loss of vision, preceding eye/head trauma, or Valsalva maneuver. His medical history was significant for well-controlled type 2 diabetes mellitus (known duration of 5 years), hypertension, hyperlipidemia, coronary artery disease, and anemia. His medications included aspirin 81 mg, furosemide, clonidine, labetalol, valsartan, glipizide, and lantus injections.

The patient’s ocular history was significant for cataracts in both eyes. On examination, best-corrected visual acuity was 20/20 in each eye with intraocular pressures of 15 mm Hg in the right eye and 14 mm Hg in the left eye. Anterior segment examination was notable for 1+ nuclear sclerotic cataracts in both eyes with red blood cells visible in the anterior chamber in the left eye. 

No PVD, retinal break, or detachment was present in the left eye with scleral depression. No background diabetic retinopathy was present in either eye. 

The patient was diagnosed with a vitreous hemorrhage associated with a vascular loop in the left eye. 

Discussion

Salient features of this case include the prominent vascular loop at the disc extending anteriorly into the vitreous and an absence of features suggestive of one of the more common etiologies of vitreous hemorrhage, such as PVD, retinal tear/detachment, proliferative diabetic retinopathy (PDR), or retinal vein occlusion.

The incidence of venous loops is 1 in 9,000 with no associated systemic conditions.^2,3 Typically unilateral, vascular loops arise at the optic disc from the central retinal artery or vein.^1-4 An arterial loop is a separate entity from a hyaloid artery.² The authors were unable to definitively determine whether the loop in this patient was arterial or venous in origin due to blockage from the associated retinal hemorrhage on FA.

Valsalva maneuver, vitreous traction, trauma, and loop torsion in patients with vascular loops can lead to amaurosis fugax, PVD, and hemorrhagic complications, such as hyphema and vitreous and retinal hemorrhages.^1,3,6-8 In addition, retinal ischemia and thrombosis from the vascular loops can lead to retinal artery or vein occlusions.^1-8 Vitreous and retinal hemorrhages, such as in this patient, are often observed with complete resolution and visual acuity returning to baseline.^4,5 For recurrent or nonresolving vitreous hemorrhages, a vitrectomy can be performed.^3,6

Conclusion

Patients with vascular loops should be educated to seek eye care if experiencing new onset floaters or visual loss.

©ASCO/Rodney White 2018

CHICAGO—Prior exposure to blinatumomab does not appear to affect the successful manufacture of KTE-C19 or its efficacy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), an investigator reported at the 2018 ASCO Annual Meeting.

The clinical benefit of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was preserved regardless of whether patients were exposed to blinatumomab, said Bijal D. Shah, MD, of Moffitt Cancer Center in Tampa, Florida.

High rates of complete response and undetectable minimal residual disease (MRD) were independent of exposure to blinatumomab, a CD19/CD3 bispecific T-cell engager.

“We feel the results of these data support KTE-C19 as an effective option for adults with refractory leukemia, regardless of prior exposure to CD19-directed therapy,” Dr Shah reported at the meeting (abstract 7006*).

The current standard of care for adults with relapsed/refractory ALL includes blinatumomab, raising the question of whether prior exposure to this CD19-directed treatment could influence the manufacture or efficacy of KTE-C19.

Sara Cooley, MD, of Masonic Medical Center, University of Minnesota in Minneapolis, said results of this analysis suggest prior blinatumomab should not be a contraindication or concern in the context of KTE-C19.

“This remains to be shown with other CAR T-cell therapies,” she said in a presentation at ASCO on cellular therapy in leukemia.

The analysis by Dr Shah and co-investigators was based on ZUMA-3 (NCT02614066), a phase 1 study including adults with relapsed/refractory ALL who received KTE-C19 at doses of 0.5, 1, or 2 x 10⁶ cells/kg.

They excluded patients in the highest dose cohort, who were required to be blinatumomab naïve, per protocol. That left 23 patients who received 0.5 or 1 x 10⁶ cells/kg, of whom 11 had prior blinatumomab exposure and 12 did not.

Best overall response appeared to be independent of prior blinatumomab treatment, with a CR rate of 72% overall, and 63% and 80% for blinatumomab-exposed and blinatumomab-naïve patients, respectively.

The rate of undetectable MRD was likewise high at 88% in the prior blinatumomab group and 100% in the no-blinatumomab group.

Product characteristics did not vary according to blinatumomab exposure, though there was a trend toward a more differentiated phenotype in those patients who had received prior CD19-directed treatment, he said.

There were no significant differences between groups in the rate of grade 3 or greater cytokine release syndrome. Neurologic events were higher in the blinatumomab-naïve patients, though a higher percentage of those patients received the 1 x 10⁶ cells/kg dose, Dr Shah reported.

Investigators also looked at CAR T levels by treatment.

“We cannot appreciate any significant differences between the blinatumomab-naïve and the blinatumomab-exposed groups,” Dr Shah told ASCO attendees.

The ZUMA-3 trial was sponsored by Kite, a Gilead Company. 

*Data in the abstract differ from the presentation.

©ASCO/Rodney White 2018

CHICAGO—Prior exposure to blinatumomab does not appear to affect the successful manufacture of KTE-C19 or its efficacy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), an investigator reported at the 2018 ASCO Annual Meeting.

The clinical benefit of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was preserved regardless of whether patients were exposed to blinatumomab, said Bijal D. Shah, MD, of Moffitt Cancer Center in Tampa, Florida.

High rates of complete response and undetectable minimal residual disease (MRD) were independent of exposure to blinatumomab, a CD19/CD3 bispecific T-cell engager.

“We feel the results of these data support KTE-C19 as an effective option for adults with refractory leukemia, regardless of prior exposure to CD19-directed therapy,” Dr Shah reported at the meeting (abstract 7006*).

The current standard of care for adults with relapsed/refractory ALL includes blinatumomab, raising the question of whether prior exposure to this CD19-directed treatment could influence the manufacture or efficacy of KTE-C19.

Sara Cooley, MD, of Masonic Medical Center, University of Minnesota in Minneapolis, said results of this analysis suggest prior blinatumomab should not be a contraindication or concern in the context of KTE-C19.

“This remains to be shown with other CAR T-cell therapies,” she said in a presentation at ASCO on cellular therapy in leukemia.

The analysis by Dr Shah and co-investigators was based on ZUMA-3 (NCT02614066), a phase 1 study including adults with relapsed/refractory ALL who received KTE-C19 at doses of 0.5, 1, or 2 x 10⁶ cells/kg.

They excluded patients in the highest dose cohort, who were required to be blinatumomab naïve, per protocol. That left 23 patients who received 0.5 or 1 x 10⁶ cells/kg, of whom 11 had prior blinatumomab exposure and 12 did not.

Best overall response appeared to be independent of prior blinatumomab treatment, with a CR rate of 72% overall, and 63% and 80% for blinatumomab-exposed and blinatumomab-naïve patients, respectively.

The rate of undetectable MRD was likewise high at 88% in the prior blinatumomab group and 100% in the no-blinatumomab group.

Product characteristics did not vary according to blinatumomab exposure, though there was a trend toward a more differentiated phenotype in those patients who had received prior CD19-directed treatment, he said.

There were no significant differences between groups in the rate of grade 3 or greater cytokine release syndrome. Neurologic events were higher in the blinatumomab-naïve patients, though a higher percentage of those patients received the 1 x 10⁶ cells/kg dose, Dr Shah reported.

Investigators also looked at CAR T levels by treatment.

“We cannot appreciate any significant differences between the blinatumomab-naïve and the blinatumomab-exposed groups,” Dr Shah told ASCO attendees.

The ZUMA-3 trial was sponsored by Kite, a Gilead Company. 

*Data in the abstract differ from the presentation.

©ASCO/Rodney White 2018

CHICAGO—Prior exposure to blinatumomab does not appear to affect the successful manufacture of KTE-C19 or its efficacy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), an investigator reported at the 2018 ASCO Annual Meeting.

The clinical benefit of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was preserved regardless of whether patients were exposed to blinatumomab, said Bijal D. Shah, MD, of Moffitt Cancer Center in Tampa, Florida.

High rates of complete response and undetectable minimal residual disease (MRD) were independent of exposure to blinatumomab, a CD19/CD3 bispecific T-cell engager.

“We feel the results of these data support KTE-C19 as an effective option for adults with refractory leukemia, regardless of prior exposure to CD19-directed therapy,” Dr Shah reported at the meeting (abstract 7006*).

The current standard of care for adults with relapsed/refractory ALL includes blinatumomab, raising the question of whether prior exposure to this CD19-directed treatment could influence the manufacture or efficacy of KTE-C19.

Sara Cooley, MD, of Masonic Medical Center, University of Minnesota in Minneapolis, said results of this analysis suggest prior blinatumomab should not be a contraindication or concern in the context of KTE-C19.

“This remains to be shown with other CAR T-cell therapies,” she said in a presentation at ASCO on cellular therapy in leukemia.

The analysis by Dr Shah and co-investigators was based on ZUMA-3 (NCT02614066), a phase 1 study including adults with relapsed/refractory ALL who received KTE-C19 at doses of 0.5, 1, or 2 x 10⁶ cells/kg.

They excluded patients in the highest dose cohort, who were required to be blinatumomab naïve, per protocol. That left 23 patients who received 0.5 or 1 x 10⁶ cells/kg, of whom 11 had prior blinatumomab exposure and 12 did not.

Best overall response appeared to be independent of prior blinatumomab treatment, with a CR rate of 72% overall, and 63% and 80% for blinatumomab-exposed and blinatumomab-naïve patients, respectively.

The rate of undetectable MRD was likewise high at 88% in the prior blinatumomab group and 100% in the no-blinatumomab group.

Product characteristics did not vary according to blinatumomab exposure, though there was a trend toward a more differentiated phenotype in those patients who had received prior CD19-directed treatment, he said.

There were no significant differences between groups in the rate of grade 3 or greater cytokine release syndrome. Neurologic events were higher in the blinatumomab-naïve patients, though a higher percentage of those patients received the 1 x 10⁶ cells/kg dose, Dr Shah reported.

Investigators also looked at CAR T levels by treatment.

“We cannot appreciate any significant differences between the blinatumomab-naïve and the blinatumomab-exposed groups,” Dr Shah told ASCO attendees.

The ZUMA-3 trial was sponsored by Kite, a Gilead Company. 

*Data in the abstract differ from the presentation.

Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.

Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.

Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.

Illicit online sales of opioids increased significantly following a 2014 regulatory decision that restricted the legal supply of opioids in the United States, results of a recent analysis show.

Opioid sales in the so-called cryptomarkets also shifted toward more potent drugs, including fentanyl, after the U.S. Drug Enforcement Administration rescheduled hydrocodone combination products, making them harder to access, authors of the analysis reported.

Those results suggest “the possibility of a causal relation” between the schedule change and sales trends on cryptomarket sites, according to James Martin, PhD, of Swinburne University, Melbourne, Australia, and co-authors.

SOURCE: Martin J, et al. BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2270.

Illicit online sales of opioids increased significantly following a 2014 regulatory decision that restricted the legal supply of opioids in the United States, results of a recent analysis show.

Opioid sales in the so-called cryptomarkets also shifted toward more potent drugs, including fentanyl, after the U.S. Drug Enforcement Administration rescheduled hydrocodone combination products, making them harder to access, authors of the analysis reported.

Those results suggest “the possibility of a causal relation” between the schedule change and sales trends on cryptomarket sites, according to James Martin, PhD, of Swinburne University, Melbourne, Australia, and co-authors.

SOURCE: Martin J, et al. BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2270.

Illicit online sales of opioids increased significantly following a 2014 regulatory decision that restricted the legal supply of opioids in the United States, results of a recent analysis show.

Opioid sales in the so-called cryptomarkets also shifted toward more potent drugs, including fentanyl, after the U.S. Drug Enforcement Administration rescheduled hydrocodone combination products, making them harder to access, authors of the analysis reported.

Those results suggest “the possibility of a causal relation” between the schedule change and sales trends on cryptomarket sites, according to James Martin, PhD, of Swinburne University, Melbourne, Australia, and co-authors.

SOURCE: Martin J, et al. BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2270.