AVAHO

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

A 21-year-old young adult presented to the ED with a 1-week history of high fever, vomiting, diarrhea, and abdominal pain. His mother was SARS-CoV-2 positive by polymerase chain reaction approximately 3 weeks prior; his PCR was negative for SARS-CoV-2.

EyeMark/thinkstockphotos.com

Following admission, he became hypotensive and tachycardic with evidence of myocarditis. His chest x-ray was normal and his O₂ saturation was 100% on room air. His clinical presentation was initially suggestive of toxic shock syndrome without a rash, but despite aggressive fluid resuscitation and broad-spectrum antibiotics, he continued to clinically deteriorate with persistent high fever and increasing cardiac stress. Echocardiography revealed biventricular dysfunction. His laboratory abnormalities included rising inflammatory markers and troponin I and B-type natriuretic peptide (BNP). A repeat PCR for SARS-CoV-2 was negative on day 2 of illness. He was diagnosed as likely having macrophage-activation syndrome (MAS) despite the atypical features (myocarditis), and he received Anakinra with no apparent response. He also was given intravenous immunoglobulin (IVIg) for his myocarditis and subsequently high-dose steroids. He became afebrile, his blood pressure stabilized, his inflammatory markers declined, and over several days he returned to normal. His COVID-19 antibody test IgG was positive on day 4 of illness.

This case challenged us for several reasons. First, the PCR from his nasopharynx was negative on two occasions, which raises the issue of how sensitive and accurate these PCR tests are for SARS-CoV-2 or are patients with COVID-19–associated hyperinflammatory syndrome still PCR positive? Second, although we have seen many adult cases with a cytokine storm picture similar to this patient, nearly all of the prior cases had chest x-ray abnormalities and hypoxia. Third, the severity of the myocardial dysfunction and rising troponin and BNP also was unusual in our experience with COVID-19 infection. Lastly, the use of antibody detection to SARS-CoV-2 enabled us to confirm recent COIVD-19 disease and see his illness as part of the likely spectrum of clinical syndromes seen with this virus.

The Lancet reported eight children, aged 4-14 years, with a hyperinflammatory shock-like syndrome in early May.¹ The cases had features similar to atypical Kawasaki disease, KD shock syndrome, and toxic shock syndrome. Each case had high fever for multiple days; diarrhea and abdominal pain was present in even children; elevated ferritin, C-reactive protein, d-dimer, increased troponins, and ventricular dysfunction also was present in seven. Most patients had no pulmonary involvement, and most tested negative for SARS-CoV-2 despite four of the eight having direct contact with a COVID-positive family member. All received IVIg and antibiotics; six received aspirin. Seven of the eight made a full recovery; one child died from a large cerebrovascular infarct.

Also in early May, the New York Times described a “mysterious” hyperinflammatory syndrome in children thought to be linked to COVID-19. A total of 76 suspected cases in children had been reported in New York state, three of whom died. The syndrome has been given the name pediatric multisystem inflammatory syndrome. The syndrome can resemble KD shock syndrome with rash; fever; conjunctivitis; hypotension; and redness in the lips, tongue and mucous membranes . It also can resemble toxic shock syndrome with abdominal pain, vomiting, and diarrhea. However, the degree of cardiac inflammation and dysfunction is substantial in many cases and usually beyond that seen in KD or toxic shock.

The syndrome is not limited to the United States. The Royal College of Pediatrics and Child Health has created a case definition:²

• A child presenting with persistent fever, inflammation (elevated C-reactive protein, neutrophilia, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurologic) with additional features.
• Exclusion of any other microbial causes such as bacterial sepsis or staphylococcal or streptococcal shock syndromes, infections known to be associated with myocarditis (such as enterovirus).
• SARS-CoV-2 testing may or may not be positive.

As with our young adult, treatment is supportive, nonspecific, and aimed at quieting the inflammatory response. The current thinking is the syndrome is seen as antibody to SARS-CoV-2 appears and frequently the nasopharyngeal PCR is negative. It is hypothesized that the syndrome occurs in genetically predisposed hosts and potentially is a late-onset inflammatory process or potentially an antibody-triggered inflammatory process. The negative PCR from nasopharyngeal specimens reflects that the onset is later in the course of disease; whether fecal samples would be COVID positive is unknown. As with our case, antibody testing for IgG against SARS-CoV-2 is appropriate to confirm COVID-19 disease and may be positive as early as day 7.

The approach needs to be team oriented and include cardiology, rheumatology, infectious diseases, and intensive care specialists working collaboratively. Such cases should be considered COVID positive despite negative PCR tests, and full personal protective equipment should be used as we do not as yet know if live virus could be found in stool. We initiated treatment with Anakinra (an interleukin-1 type-1 receptor inhibitor) as part of our treatment protocol for MAS; we did not appreciate a response. He then received IVIg and high-dose steroids, and he recovered over several days with improved cardiac function and stable blood pressure.

Clearly, we have a steep learning curve about the multisystem hyperinflammatory syndrome emerging in association with SARS-CoV-2 infection. What is the pathogenesis? Is SARS-CoV-2 causative or just an associated finding? Who are the at-risk children, adolescents, and adults? Is there a genetic predisposition? What therapies work best? The eight cases described in London all received IVIg, as did our case, and all but one improved and survived. In adults we have seen substantial inflammation with elevated C-reactive protein (often as high as 300), ferritin, lactate dehydrogenase, triglycerides, fibrinogen, and d-dimers, but nearly all have extensive pulmonary disease, hypoxia, and are SARS-CoV-2 positive by PCR. Influenza is also associated with a cytokine storm syndrome in adolescents and young adults.³ The mechanisms influenza virus uses to initiate a cytokine storm and strategies for immunomodulatory treatment may provide insights into COVID-19–associated multisystem hyperinflammatory syndrome.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician in pediatric infectious diseases at Boston Medical Center. Dr. Camelo is a senior fellow in pediatric infectious diseases at Boston Medical Center. They have no relevant financial disclosures. Email them at [email protected].

References

1. Riphagen S et al. Lancet. 2020 May 6. doi: 10.1016/S0140-6736(20)31094-1.

2. Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.

3. Liu Q et al.Cell Mol Immunol. 2016 Jan;13(1):3-10.

A 21-year-old young adult presented to the ED with a 1-week history of high fever, vomiting, diarrhea, and abdominal pain. His mother was SARS-CoV-2 positive by polymerase chain reaction approximately 3 weeks prior; his PCR was negative for SARS-CoV-2.

EyeMark/thinkstockphotos.com

Following admission, he became hypotensive and tachycardic with evidence of myocarditis. His chest x-ray was normal and his O₂ saturation was 100% on room air. His clinical presentation was initially suggestive of toxic shock syndrome without a rash, but despite aggressive fluid resuscitation and broad-spectrum antibiotics, he continued to clinically deteriorate with persistent high fever and increasing cardiac stress. Echocardiography revealed biventricular dysfunction. His laboratory abnormalities included rising inflammatory markers and troponin I and B-type natriuretic peptide (BNP). A repeat PCR for SARS-CoV-2 was negative on day 2 of illness. He was diagnosed as likely having macrophage-activation syndrome (MAS) despite the atypical features (myocarditis), and he received Anakinra with no apparent response. He also was given intravenous immunoglobulin (IVIg) for his myocarditis and subsequently high-dose steroids. He became afebrile, his blood pressure stabilized, his inflammatory markers declined, and over several days he returned to normal. His COVID-19 antibody test IgG was positive on day 4 of illness.

This case challenged us for several reasons. First, the PCR from his nasopharynx was negative on two occasions, which raises the issue of how sensitive and accurate these PCR tests are for SARS-CoV-2 or are patients with COVID-19–associated hyperinflammatory syndrome still PCR positive? Second, although we have seen many adult cases with a cytokine storm picture similar to this patient, nearly all of the prior cases had chest x-ray abnormalities and hypoxia. Third, the severity of the myocardial dysfunction and rising troponin and BNP also was unusual in our experience with COVID-19 infection. Lastly, the use of antibody detection to SARS-CoV-2 enabled us to confirm recent COIVD-19 disease and see his illness as part of the likely spectrum of clinical syndromes seen with this virus.

The Lancet reported eight children, aged 4-14 years, with a hyperinflammatory shock-like syndrome in early May.¹ The cases had features similar to atypical Kawasaki disease, KD shock syndrome, and toxic shock syndrome. Each case had high fever for multiple days; diarrhea and abdominal pain was present in even children; elevated ferritin, C-reactive protein, d-dimer, increased troponins, and ventricular dysfunction also was present in seven. Most patients had no pulmonary involvement, and most tested negative for SARS-CoV-2 despite four of the eight having direct contact with a COVID-positive family member. All received IVIg and antibiotics; six received aspirin. Seven of the eight made a full recovery; one child died from a large cerebrovascular infarct.

Also in early May, the New York Times described a “mysterious” hyperinflammatory syndrome in children thought to be linked to COVID-19. A total of 76 suspected cases in children had been reported in New York state, three of whom died. The syndrome has been given the name pediatric multisystem inflammatory syndrome. The syndrome can resemble KD shock syndrome with rash; fever; conjunctivitis; hypotension; and redness in the lips, tongue and mucous membranes . It also can resemble toxic shock syndrome with abdominal pain, vomiting, and diarrhea. However, the degree of cardiac inflammation and dysfunction is substantial in many cases and usually beyond that seen in KD or toxic shock.

The syndrome is not limited to the United States. The Royal College of Pediatrics and Child Health has created a case definition:²

• A child presenting with persistent fever, inflammation (elevated C-reactive protein, neutrophilia, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurologic) with additional features.
• Exclusion of any other microbial causes such as bacterial sepsis or staphylococcal or streptococcal shock syndromes, infections known to be associated with myocarditis (such as enterovirus).
• SARS-CoV-2 testing may or may not be positive.

As with our young adult, treatment is supportive, nonspecific, and aimed at quieting the inflammatory response. The current thinking is the syndrome is seen as antibody to SARS-CoV-2 appears and frequently the nasopharyngeal PCR is negative. It is hypothesized that the syndrome occurs in genetically predisposed hosts and potentially is a late-onset inflammatory process or potentially an antibody-triggered inflammatory process. The negative PCR from nasopharyngeal specimens reflects that the onset is later in the course of disease; whether fecal samples would be COVID positive is unknown. As with our case, antibody testing for IgG against SARS-CoV-2 is appropriate to confirm COVID-19 disease and may be positive as early as day 7.

The approach needs to be team oriented and include cardiology, rheumatology, infectious diseases, and intensive care specialists working collaboratively. Such cases should be considered COVID positive despite negative PCR tests, and full personal protective equipment should be used as we do not as yet know if live virus could be found in stool. We initiated treatment with Anakinra (an interleukin-1 type-1 receptor inhibitor) as part of our treatment protocol for MAS; we did not appreciate a response. He then received IVIg and high-dose steroids, and he recovered over several days with improved cardiac function and stable blood pressure.

Clearly, we have a steep learning curve about the multisystem hyperinflammatory syndrome emerging in association with SARS-CoV-2 infection. What is the pathogenesis? Is SARS-CoV-2 causative or just an associated finding? Who are the at-risk children, adolescents, and adults? Is there a genetic predisposition? What therapies work best? The eight cases described in London all received IVIg, as did our case, and all but one improved and survived. In adults we have seen substantial inflammation with elevated C-reactive protein (often as high as 300), ferritin, lactate dehydrogenase, triglycerides, fibrinogen, and d-dimers, but nearly all have extensive pulmonary disease, hypoxia, and are SARS-CoV-2 positive by PCR. Influenza is also associated with a cytokine storm syndrome in adolescents and young adults.³ The mechanisms influenza virus uses to initiate a cytokine storm and strategies for immunomodulatory treatment may provide insights into COVID-19–associated multisystem hyperinflammatory syndrome.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician in pediatric infectious diseases at Boston Medical Center. Dr. Camelo is a senior fellow in pediatric infectious diseases at Boston Medical Center. They have no relevant financial disclosures. Email them at [email protected].

References

1. Riphagen S et al. Lancet. 2020 May 6. doi: 10.1016/S0140-6736(20)31094-1.

2. Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.

3. Liu Q et al.Cell Mol Immunol. 2016 Jan;13(1):3-10.

A 21-year-old young adult presented to the ED with a 1-week history of high fever, vomiting, diarrhea, and abdominal pain. His mother was SARS-CoV-2 positive by polymerase chain reaction approximately 3 weeks prior; his PCR was negative for SARS-CoV-2.

EyeMark/thinkstockphotos.com

Following admission, he became hypotensive and tachycardic with evidence of myocarditis. His chest x-ray was normal and his O₂ saturation was 100% on room air. His clinical presentation was initially suggestive of toxic shock syndrome without a rash, but despite aggressive fluid resuscitation and broad-spectrum antibiotics, he continued to clinically deteriorate with persistent high fever and increasing cardiac stress. Echocardiography revealed biventricular dysfunction. His laboratory abnormalities included rising inflammatory markers and troponin I and B-type natriuretic peptide (BNP). A repeat PCR for SARS-CoV-2 was negative on day 2 of illness. He was diagnosed as likely having macrophage-activation syndrome (MAS) despite the atypical features (myocarditis), and he received Anakinra with no apparent response. He also was given intravenous immunoglobulin (IVIg) for his myocarditis and subsequently high-dose steroids. He became afebrile, his blood pressure stabilized, his inflammatory markers declined, and over several days he returned to normal. His COVID-19 antibody test IgG was positive on day 4 of illness.

This case challenged us for several reasons. First, the PCR from his nasopharynx was negative on two occasions, which raises the issue of how sensitive and accurate these PCR tests are for SARS-CoV-2 or are patients with COVID-19–associated hyperinflammatory syndrome still PCR positive? Second, although we have seen many adult cases with a cytokine storm picture similar to this patient, nearly all of the prior cases had chest x-ray abnormalities and hypoxia. Third, the severity of the myocardial dysfunction and rising troponin and BNP also was unusual in our experience with COVID-19 infection. Lastly, the use of antibody detection to SARS-CoV-2 enabled us to confirm recent COIVD-19 disease and see his illness as part of the likely spectrum of clinical syndromes seen with this virus.

The Lancet reported eight children, aged 4-14 years, with a hyperinflammatory shock-like syndrome in early May.¹ The cases had features similar to atypical Kawasaki disease, KD shock syndrome, and toxic shock syndrome. Each case had high fever for multiple days; diarrhea and abdominal pain was present in even children; elevated ferritin, C-reactive protein, d-dimer, increased troponins, and ventricular dysfunction also was present in seven. Most patients had no pulmonary involvement, and most tested negative for SARS-CoV-2 despite four of the eight having direct contact with a COVID-positive family member. All received IVIg and antibiotics; six received aspirin. Seven of the eight made a full recovery; one child died from a large cerebrovascular infarct.

Also in early May, the New York Times described a “mysterious” hyperinflammatory syndrome in children thought to be linked to COVID-19. A total of 76 suspected cases in children had been reported in New York state, three of whom died. The syndrome has been given the name pediatric multisystem inflammatory syndrome. The syndrome can resemble KD shock syndrome with rash; fever; conjunctivitis; hypotension; and redness in the lips, tongue and mucous membranes . It also can resemble toxic shock syndrome with abdominal pain, vomiting, and diarrhea. However, the degree of cardiac inflammation and dysfunction is substantial in many cases and usually beyond that seen in KD or toxic shock.

The syndrome is not limited to the United States. The Royal College of Pediatrics and Child Health has created a case definition:²

• A child presenting with persistent fever, inflammation (elevated C-reactive protein, neutrophilia, and lymphopenia) and evidence of single or multiorgan dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurologic) with additional features.
• Exclusion of any other microbial causes such as bacterial sepsis or staphylococcal or streptococcal shock syndromes, infections known to be associated with myocarditis (such as enterovirus).
• SARS-CoV-2 testing may or may not be positive.

As with our young adult, treatment is supportive, nonspecific, and aimed at quieting the inflammatory response. The current thinking is the syndrome is seen as antibody to SARS-CoV-2 appears and frequently the nasopharyngeal PCR is negative. It is hypothesized that the syndrome occurs in genetically predisposed hosts and potentially is a late-onset inflammatory process or potentially an antibody-triggered inflammatory process. The negative PCR from nasopharyngeal specimens reflects that the onset is later in the course of disease; whether fecal samples would be COVID positive is unknown. As with our case, antibody testing for IgG against SARS-CoV-2 is appropriate to confirm COVID-19 disease and may be positive as early as day 7.

The approach needs to be team oriented and include cardiology, rheumatology, infectious diseases, and intensive care specialists working collaboratively. Such cases should be considered COVID positive despite negative PCR tests, and full personal protective equipment should be used as we do not as yet know if live virus could be found in stool. We initiated treatment with Anakinra (an interleukin-1 type-1 receptor inhibitor) as part of our treatment protocol for MAS; we did not appreciate a response. He then received IVIg and high-dose steroids, and he recovered over several days with improved cardiac function and stable blood pressure.

Clearly, we have a steep learning curve about the multisystem hyperinflammatory syndrome emerging in association with SARS-CoV-2 infection. What is the pathogenesis? Is SARS-CoV-2 causative or just an associated finding? Who are the at-risk children, adolescents, and adults? Is there a genetic predisposition? What therapies work best? The eight cases described in London all received IVIg, as did our case, and all but one improved and survived. In adults we have seen substantial inflammation with elevated C-reactive protein (often as high as 300), ferritin, lactate dehydrogenase, triglycerides, fibrinogen, and d-dimers, but nearly all have extensive pulmonary disease, hypoxia, and are SARS-CoV-2 positive by PCR. Influenza is also associated with a cytokine storm syndrome in adolescents and young adults.³ The mechanisms influenza virus uses to initiate a cytokine storm and strategies for immunomodulatory treatment may provide insights into COVID-19–associated multisystem hyperinflammatory syndrome.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician in pediatric infectious diseases at Boston Medical Center. Dr. Camelo is a senior fellow in pediatric infectious diseases at Boston Medical Center. They have no relevant financial disclosures. Email them at [email protected].

References

1. Riphagen S et al. Lancet. 2020 May 6. doi: 10.1016/S0140-6736(20)31094-1.

2. Royal College of Paediatrics and Child Health Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.

3. Liu Q et al.Cell Mol Immunol. 2016 Jan;13(1):3-10.

The application of improved chemotherapy regimens and novel chemotherapy for acute lymphoblastic leukemia (ALL) has increased the complete remission rate to 85%-90%, however, secondary ALL is common, and the prolonged long-term survival rate is only 30%-50% among ALL patients.

Favorable outcomes decrease with increasing age, and overall survival is greater for adult patients with de novo ALL, compared with patients with secondary ALL, according to the Jiansheng Zhong of the department of hematology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China, and colleagues in a new study published online in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia (sALL) group. They used propensity matching before assessing overall survival between the two groups.

Demographically, the results showed that women ALL patients had a lower risk of death than men [hazard ratio (HR) = .93, P < .01], and that the mortality in blacks was higher than that of whites (HR = 1.29, P < .001).

For both ALL groups, patients aged 45-75 years and patients 75 years and older had a higher risk of death than younger patients (HR = 1.82, P < .001 and HR = 3.85, P < .001, respectively).

Although the mean age of de novo ALL group was significantly less than that of the sALL group (51.1 vs. 60.3 years, P < .001), after the propensity matching, the 1-, 2-, 3-, 4- and 5-year overall survival of the de novo ALL group was higher than that of the sALL group at all ages (18-75 years, P < .001).

The authors speculated that one reason for the across-the-board increased mortality in sALL, compared with de novo ALL, might be the fact that sALL patients have been reported to have more MLL gene rearrangements and chromosomal aberrations than are found in de novo ALL. This has previously been suggested as the reason for poor prognosis in secondary ALL patients.

One limitation of the study mentioned by the authors was the lack of individualized chemotherapy data available for analysis. “Considering that the features of sALL and chemotherapeutic modalities or therapy protocols may affect the mortality of sALL, more work is needed to be done in the future to demonstrate the association between chemotherapy and the prognosis of ALL patients, and the influence of cytogenetic lesions and molecular characteristics on sALL,” they concluded.

The authors declared they had no conflicts of interest.
 

[email protected]

SOURCE: Zhong J et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 30; doi.org/10.1016/j.clml.2020.04.013.

The application of improved chemotherapy regimens and novel chemotherapy for acute lymphoblastic leukemia (ALL) has increased the complete remission rate to 85%-90%, however, secondary ALL is common, and the prolonged long-term survival rate is only 30%-50% among ALL patients.

Favorable outcomes decrease with increasing age, and overall survival is greater for adult patients with de novo ALL, compared with patients with secondary ALL, according to the Jiansheng Zhong of the department of hematology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China, and colleagues in a new study published online in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia (sALL) group. They used propensity matching before assessing overall survival between the two groups.

Demographically, the results showed that women ALL patients had a lower risk of death than men [hazard ratio (HR) = .93, P < .01], and that the mortality in blacks was higher than that of whites (HR = 1.29, P < .001).

For both ALL groups, patients aged 45-75 years and patients 75 years and older had a higher risk of death than younger patients (HR = 1.82, P < .001 and HR = 3.85, P < .001, respectively).

Although the mean age of de novo ALL group was significantly less than that of the sALL group (51.1 vs. 60.3 years, P < .001), after the propensity matching, the 1-, 2-, 3-, 4- and 5-year overall survival of the de novo ALL group was higher than that of the sALL group at all ages (18-75 years, P < .001).

The authors speculated that one reason for the across-the-board increased mortality in sALL, compared with de novo ALL, might be the fact that sALL patients have been reported to have more MLL gene rearrangements and chromosomal aberrations than are found in de novo ALL. This has previously been suggested as the reason for poor prognosis in secondary ALL patients.

One limitation of the study mentioned by the authors was the lack of individualized chemotherapy data available for analysis. “Considering that the features of sALL and chemotherapeutic modalities or therapy protocols may affect the mortality of sALL, more work is needed to be done in the future to demonstrate the association between chemotherapy and the prognosis of ALL patients, and the influence of cytogenetic lesions and molecular characteristics on sALL,” they concluded.

The authors declared they had no conflicts of interest.
 

[email protected]

SOURCE: Zhong J et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 30; doi.org/10.1016/j.clml.2020.04.013.

The application of improved chemotherapy regimens and novel chemotherapy for acute lymphoblastic leukemia (ALL) has increased the complete remission rate to 85%-90%, however, secondary ALL is common, and the prolonged long-term survival rate is only 30%-50% among ALL patients.

Favorable outcomes decrease with increasing age, and overall survival is greater for adult patients with de novo ALL, compared with patients with secondary ALL, according to the Jiansheng Zhong of the department of hematology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China, and colleagues in a new study published online in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia (sALL) group. They used propensity matching before assessing overall survival between the two groups.

Demographically, the results showed that women ALL patients had a lower risk of death than men [hazard ratio (HR) = .93, P < .01], and that the mortality in blacks was higher than that of whites (HR = 1.29, P < .001).

For both ALL groups, patients aged 45-75 years and patients 75 years and older had a higher risk of death than younger patients (HR = 1.82, P < .001 and HR = 3.85, P < .001, respectively).

Although the mean age of de novo ALL group was significantly less than that of the sALL group (51.1 vs. 60.3 years, P < .001), after the propensity matching, the 1-, 2-, 3-, 4- and 5-year overall survival of the de novo ALL group was higher than that of the sALL group at all ages (18-75 years, P < .001).

The authors speculated that one reason for the across-the-board increased mortality in sALL, compared with de novo ALL, might be the fact that sALL patients have been reported to have more MLL gene rearrangements and chromosomal aberrations than are found in de novo ALL. This has previously been suggested as the reason for poor prognosis in secondary ALL patients.

One limitation of the study mentioned by the authors was the lack of individualized chemotherapy data available for analysis. “Considering that the features of sALL and chemotherapeutic modalities or therapy protocols may affect the mortality of sALL, more work is needed to be done in the future to demonstrate the association between chemotherapy and the prognosis of ALL patients, and the influence of cytogenetic lesions and molecular characteristics on sALL,” they concluded.

The authors declared they had no conflicts of interest.
 

[email protected]

SOURCE: Zhong J et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 30; doi.org/10.1016/j.clml.2020.04.013.

A blood test detected 11 of 11 cases of colorectal cancer in a study involving 354 patients, and also spotted a majority of cases – 40 out of 53 – in which participants had advanced adenomas, an investigator said.

Results from a single-center study of CellMax Life’s FirstSight blood test were released as a poster as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

For a study conducted at one site, the Veterans Affairs Palo Alto (Calif.) Healthcare System, Shai Friedland, MD, and colleagues recruited 354 patients between ages 45 and 80 who were scheduled for elective colonoscopy. The researchers excluded people with a personal history of cancer or inflammatory bowel disease. They used CellMax’s FirstSight test on blood samples from the study participants.

The FirstSight test result was positive for colorectal cancer in all 11 patients in the study who were found by colonoscopy to have this condition, said Dr. Friedland, who is a professor of medicine at Stanford (Calif.) University and chief of gastroenterology at the VA Palo Alto Healthcare System. Thus, the test showed a sensitivity of 100% in this instance.

Among the 53 study participants found by colonoscopy to have advanced adenoma, 40 were positive on FirstSight; thus, so the test has a sensitivity of 75.5% for this result.

Among 79 patients who had negative colonoscopy results, meaning they were judged free of cancer or polyps, the test showed 8 as having signs of disease or growths.

“If you had a large adenoma that was removed years ago and now you have a negative colonoscopy, your score might still be high,” Dr. Friedland said in a recorded presentation for DDW. “In other words, the changes that are detectable in your blood might persist even after the polypectomy.”

He said there are plans to soon start a large-scale multicenter study of the CellMax assay.

“The blood test has the potential to fill an unmet need by giving patients a highly sensitive convenient option for colorectal cancer screening,” he said.

CellMax already is seeking to position its test as a more convenient alternative to either colonoscopy or the Cologuard screening test. Many patients put off cancer screening because of the need to take time off from work and the invasive nature of colonoscopy. Exact Sciences has used direct-to-consumer advertising to promote its Cologuard home-based test as a more convenient alternative to colonoscopy, but its product requires patients to collect their own stool samples and mail them to a lab, a process many people find off-putting.

Public health advocates, including the U.S. Preventive Services Task Force (USPSTF), have for years been pressing for wider screening of American adults for colon cancer. USPSTF is in the midst of updating its recommendations on colon cancer. In announcing its latest update of these recommendations in 2016, USPSTF said “the best screening test is the one that gets done” (JAMA. 2016;315[23]:2564-75).

USPSTF pressed for maximizing the total proportion of the eligible population, a point Dr. Friedland echoed in a CellMax press release.

“For colon cancer screening to be most effective, it is essential to detect precancerous polyps and then perform a colonoscopy to remove the polyps,” said Dr. Friedland in the CellMax press release. “Giving patients the option of getting a blood test for screening would undoubtedly increase compliance and thereby reduce mortality from colorectal cancer.”

In the DDW presentation, Dr. Friedland and colleagues also said the CellMax test showed greater sensitivity (100%) for colorectal cancer and advanced precancerous lesions (75.5%) than did Cologuard (92.3% for colorectal cancer and 42.4% for advanced precancerous lesions).

Cara Connelly, Director of Public Relations and Corporate Communications for Exact Sciences said that the company “is dedicated to getting more people screened for colorectal cancer and applaud the researchers for their efforts. We look forward to hearing more about the performance of this test in a prospective multisite study with nonsymptomatic patients.”

Naresh T. Gunaratnam, MD, a gastroenterologist and research director at Huron Gastro in Ypsilanti, Mich., said he is concerned that aggressive promotion of alternative tests may obscure the benefits of colonoscopy. Dr. Gunaratnam, a 2019 winner of the American Gastroenterological Association (AGA) Distinguished Clinician Award, has been a public critic of the marketing of colon cancer tests, which emphasize the convenience of these products. When asked by MDedge to comment on the CellMax-funded study, Dr. Gunaratnam said alternative tests do have a place for the care of patients who cannot or will not have a colonoscopy.

“But if you convince a patient who would be willing to have a colonoscopy not to, that’s a disservice,” he said.

“If you want the best test, the one that is best at finding cancers and finding polyps and the only one that can remove the polyp, that’s colonoscopy,” Dr. Gunaratnam added. “One day there may be a pill you can swallow that blows up the polyps, but we’re not there yet. We have to mechanically remove them.”

SOURCE: Friedland S et al. DDW 2020, eposter 575.

A blood test detected 11 of 11 cases of colorectal cancer in a study involving 354 patients, and also spotted a majority of cases – 40 out of 53 – in which participants had advanced adenomas, an investigator said.

Results from a single-center study of CellMax Life’s FirstSight blood test were released as a poster as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

For a study conducted at one site, the Veterans Affairs Palo Alto (Calif.) Healthcare System, Shai Friedland, MD, and colleagues recruited 354 patients between ages 45 and 80 who were scheduled for elective colonoscopy. The researchers excluded people with a personal history of cancer or inflammatory bowel disease. They used CellMax’s FirstSight test on blood samples from the study participants.

The FirstSight test result was positive for colorectal cancer in all 11 patients in the study who were found by colonoscopy to have this condition, said Dr. Friedland, who is a professor of medicine at Stanford (Calif.) University and chief of gastroenterology at the VA Palo Alto Healthcare System. Thus, the test showed a sensitivity of 100% in this instance.

Among the 53 study participants found by colonoscopy to have advanced adenoma, 40 were positive on FirstSight; thus, so the test has a sensitivity of 75.5% for this result.

Among 79 patients who had negative colonoscopy results, meaning they were judged free of cancer or polyps, the test showed 8 as having signs of disease or growths.

“If you had a large adenoma that was removed years ago and now you have a negative colonoscopy, your score might still be high,” Dr. Friedland said in a recorded presentation for DDW. “In other words, the changes that are detectable in your blood might persist even after the polypectomy.”

He said there are plans to soon start a large-scale multicenter study of the CellMax assay.

“The blood test has the potential to fill an unmet need by giving patients a highly sensitive convenient option for colorectal cancer screening,” he said.

CellMax already is seeking to position its test as a more convenient alternative to either colonoscopy or the Cologuard screening test. Many patients put off cancer screening because of the need to take time off from work and the invasive nature of colonoscopy. Exact Sciences has used direct-to-consumer advertising to promote its Cologuard home-based test as a more convenient alternative to colonoscopy, but its product requires patients to collect their own stool samples and mail them to a lab, a process many people find off-putting.

Public health advocates, including the U.S. Preventive Services Task Force (USPSTF), have for years been pressing for wider screening of American adults for colon cancer. USPSTF is in the midst of updating its recommendations on colon cancer. In announcing its latest update of these recommendations in 2016, USPSTF said “the best screening test is the one that gets done” (JAMA. 2016;315[23]:2564-75).

USPSTF pressed for maximizing the total proportion of the eligible population, a point Dr. Friedland echoed in a CellMax press release.

“For colon cancer screening to be most effective, it is essential to detect precancerous polyps and then perform a colonoscopy to remove the polyps,” said Dr. Friedland in the CellMax press release. “Giving patients the option of getting a blood test for screening would undoubtedly increase compliance and thereby reduce mortality from colorectal cancer.”

In the DDW presentation, Dr. Friedland and colleagues also said the CellMax test showed greater sensitivity (100%) for colorectal cancer and advanced precancerous lesions (75.5%) than did Cologuard (92.3% for colorectal cancer and 42.4% for advanced precancerous lesions).

Cara Connelly, Director of Public Relations and Corporate Communications for Exact Sciences said that the company “is dedicated to getting more people screened for colorectal cancer and applaud the researchers for their efforts. We look forward to hearing more about the performance of this test in a prospective multisite study with nonsymptomatic patients.”

Naresh T. Gunaratnam, MD, a gastroenterologist and research director at Huron Gastro in Ypsilanti, Mich., said he is concerned that aggressive promotion of alternative tests may obscure the benefits of colonoscopy. Dr. Gunaratnam, a 2019 winner of the American Gastroenterological Association (AGA) Distinguished Clinician Award, has been a public critic of the marketing of colon cancer tests, which emphasize the convenience of these products. When asked by MDedge to comment on the CellMax-funded study, Dr. Gunaratnam said alternative tests do have a place for the care of patients who cannot or will not have a colonoscopy.

“But if you convince a patient who would be willing to have a colonoscopy not to, that’s a disservice,” he said.

“If you want the best test, the one that is best at finding cancers and finding polyps and the only one that can remove the polyp, that’s colonoscopy,” Dr. Gunaratnam added. “One day there may be a pill you can swallow that blows up the polyps, but we’re not there yet. We have to mechanically remove them.”

SOURCE: Friedland S et al. DDW 2020, eposter 575.

A blood test detected 11 of 11 cases of colorectal cancer in a study involving 354 patients, and also spotted a majority of cases – 40 out of 53 – in which participants had advanced adenomas, an investigator said.

Results from a single-center study of CellMax Life’s FirstSight blood test were released as a poster as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

For a study conducted at one site, the Veterans Affairs Palo Alto (Calif.) Healthcare System, Shai Friedland, MD, and colleagues recruited 354 patients between ages 45 and 80 who were scheduled for elective colonoscopy. The researchers excluded people with a personal history of cancer or inflammatory bowel disease. They used CellMax’s FirstSight test on blood samples from the study participants.

The FirstSight test result was positive for colorectal cancer in all 11 patients in the study who were found by colonoscopy to have this condition, said Dr. Friedland, who is a professor of medicine at Stanford (Calif.) University and chief of gastroenterology at the VA Palo Alto Healthcare System. Thus, the test showed a sensitivity of 100% in this instance.

Among the 53 study participants found by colonoscopy to have advanced adenoma, 40 were positive on FirstSight; thus, so the test has a sensitivity of 75.5% for this result.

Among 79 patients who had negative colonoscopy results, meaning they were judged free of cancer or polyps, the test showed 8 as having signs of disease or growths.

“If you had a large adenoma that was removed years ago and now you have a negative colonoscopy, your score might still be high,” Dr. Friedland said in a recorded presentation for DDW. “In other words, the changes that are detectable in your blood might persist even after the polypectomy.”

He said there are plans to soon start a large-scale multicenter study of the CellMax assay.

“The blood test has the potential to fill an unmet need by giving patients a highly sensitive convenient option for colorectal cancer screening,” he said.

CellMax already is seeking to position its test as a more convenient alternative to either colonoscopy or the Cologuard screening test. Many patients put off cancer screening because of the need to take time off from work and the invasive nature of colonoscopy. Exact Sciences has used direct-to-consumer advertising to promote its Cologuard home-based test as a more convenient alternative to colonoscopy, but its product requires patients to collect their own stool samples and mail them to a lab, a process many people find off-putting.

Public health advocates, including the U.S. Preventive Services Task Force (USPSTF), have for years been pressing for wider screening of American adults for colon cancer. USPSTF is in the midst of updating its recommendations on colon cancer. In announcing its latest update of these recommendations in 2016, USPSTF said “the best screening test is the one that gets done” (JAMA. 2016;315[23]:2564-75).

USPSTF pressed for maximizing the total proportion of the eligible population, a point Dr. Friedland echoed in a CellMax press release.

“For colon cancer screening to be most effective, it is essential to detect precancerous polyps and then perform a colonoscopy to remove the polyps,” said Dr. Friedland in the CellMax press release. “Giving patients the option of getting a blood test for screening would undoubtedly increase compliance and thereby reduce mortality from colorectal cancer.”

In the DDW presentation, Dr. Friedland and colleagues also said the CellMax test showed greater sensitivity (100%) for colorectal cancer and advanced precancerous lesions (75.5%) than did Cologuard (92.3% for colorectal cancer and 42.4% for advanced precancerous lesions).

Cara Connelly, Director of Public Relations and Corporate Communications for Exact Sciences said that the company “is dedicated to getting more people screened for colorectal cancer and applaud the researchers for their efforts. We look forward to hearing more about the performance of this test in a prospective multisite study with nonsymptomatic patients.”

Naresh T. Gunaratnam, MD, a gastroenterologist and research director at Huron Gastro in Ypsilanti, Mich., said he is concerned that aggressive promotion of alternative tests may obscure the benefits of colonoscopy. Dr. Gunaratnam, a 2019 winner of the American Gastroenterological Association (AGA) Distinguished Clinician Award, has been a public critic of the marketing of colon cancer tests, which emphasize the convenience of these products. When asked by MDedge to comment on the CellMax-funded study, Dr. Gunaratnam said alternative tests do have a place for the care of patients who cannot or will not have a colonoscopy.

“But if you convince a patient who would be willing to have a colonoscopy not to, that’s a disservice,” he said.

“If you want the best test, the one that is best at finding cancers and finding polyps and the only one that can remove the polyp, that’s colonoscopy,” Dr. Gunaratnam added. “One day there may be a pill you can swallow that blows up the polyps, but we’re not there yet. We have to mechanically remove them.”

SOURCE: Friedland S et al. DDW 2020, eposter 575.

No one really knows how long the COVID-19 pandemic will endure, and it’s highly likely personal protective equipment (PPE) will be a pressing priority for months to come. Ensuring supplies has become a creative endeavor, with new partnerships forming to fill gaps.

The US Department of Defense (DoD), for instance, has signed a $126 million contract with 3M to produce 26 million N95 masks per month, starting in October, according to DoD spokesperson Lt. Col. Mike Andrews. 3M will expedite design, procurement, production facilities, and equipment to increase respirator production by at least 312 million annually within the next 12 months. The company is ramping up: It has already placed orders for raw material and 2 new N95 manufacturing lines, in addition to beginning initial production in Wisconsin and expanding a facility in South Dakota.

The project, funded through the CARES Act, is spearheaded by the Joint Acquisition Task Force, which serves as the DoD’s overarching framework for acquisition support.

The US Department of Veterans Affairs (VA) also has a new procurement partner: New Hampshire. The state’s leadership, community business leaders and the VA Secretary’s Center for Strategic Partnerships secured millions of masks for VA workforce nationwide.

“Once again, New Hampshire stands out as a leader in our nation for its collaborative nature benefiting veterans,” said Acting VA Deputy Secretary Pamela Powers. “Governor Sununu and Dean Kamen [a New Hampshire-based inventor] made it possible for VA to purchase 4.5 million masks…. Having these additional resources is truly incredible and on behalf of the department, I offer our sincere gratitude.”

A FedEx cargo plane stocked with 110,000 pounds of PPE landed at Manchester Airport, the third such shipment to arrive in the state. “It is a tribute to our state that we were more aggressive and proactive in our approach to readiness from the get-go,” said Maj. Gen. David J. Mikolaities, the adjutant general of the New Hampshire Army National Guard, which stood ready to support deployment of the new supplies. “We didn’t wait for the need to occur; we secured the supplies so when and if the demand hits we’d be ready with our PPE distribution.”

The need has been getting stronger. More than 1,300 VA employees have tested positive for COVID-19 according to the VA, and 28 are reported to have died. The cases span 114 VA facilities, but with infections affecting less than 1% of the VA health care workforce, the rate is lower at VA than at several large health care systems, including a 4.4% infection rate at University of Washington Medicine and 2.1% of the Detroit-based Henry Ford Health System.

VA nurses and other hospital employees had been warning for weeks that they did not have enough protective gear. Although VA officials denied this, an April 16 memo sent to network directors by the VA's deputy under secretary for health for operations and management indicated the agency was implementing conservation procedures to stretch supplies.

According to The Washington Post, some of those conservation measures were necessary because FEMA had diverted millions of masks and other PPE that VA had ordered away from the department. In a Post interview, Richard Stone, MD, VHA Executive in Charge, acknowledged that he’d been forced to move to “austerity levels” at some hospitals. (At some facilities, VA employees were provided with one surgical mask per week and N95s were reportedly nearly impossible to find.)

Stone said FEMA had directed vendors with equipment on order from VA to instead send it to FEMA to replenish the government’s rapidly depleting emergency stockpile: “I had 5 million masks incoming that disappeared.” At the time, Stone told the Post, the VA’s four-week supply of equipment was almost gone, and the system was burning through about 200,000 masks in a day. The supply system was responding to FEMA, he said. “I couldn’t tell you when my next delivery was coming in.”

According to a recent ProPublica report, the VA has tried other means to acquire PPE, with limited success. The VA contracted to pay $34.5 million for 6 million N95 respirators, a 350% markup on the normal cost of the masks. Unfortunately, even at that price, the contractor received higher bids for the masks and the VA ended up cancelling the contract.

In an effort to reassure veterans and employees, the VA issued a press release insisting that it had stable and “sufficient” supplies on May 13. According to the release, the VA had on hand “the capacity to take in 12,215 critical and non-critical patients,” and its occupancy rates “remain steady at 35-40% nationwide in both acute care and intensive care units (ICUs).” The release also asserted that the “VA’s stock of medical supplies remains robust with millions of N95 masks on hand,” and 1,943 ICU ventilators.

No one really knows how long the COVID-19 pandemic will endure, and it’s highly likely personal protective equipment (PPE) will be a pressing priority for months to come. Ensuring supplies has become a creative endeavor, with new partnerships forming to fill gaps.

The US Department of Defense (DoD), for instance, has signed a $126 million contract with 3M to produce 26 million N95 masks per month, starting in October, according to DoD spokesperson Lt. Col. Mike Andrews. 3M will expedite design, procurement, production facilities, and equipment to increase respirator production by at least 312 million annually within the next 12 months. The company is ramping up: It has already placed orders for raw material and 2 new N95 manufacturing lines, in addition to beginning initial production in Wisconsin and expanding a facility in South Dakota.

The project, funded through the CARES Act, is spearheaded by the Joint Acquisition Task Force, which serves as the DoD’s overarching framework for acquisition support.

The US Department of Veterans Affairs (VA) also has a new procurement partner: New Hampshire. The state’s leadership, community business leaders and the VA Secretary’s Center for Strategic Partnerships secured millions of masks for VA workforce nationwide.

“Once again, New Hampshire stands out as a leader in our nation for its collaborative nature benefiting veterans,” said Acting VA Deputy Secretary Pamela Powers. “Governor Sununu and Dean Kamen [a New Hampshire-based inventor] made it possible for VA to purchase 4.5 million masks…. Having these additional resources is truly incredible and on behalf of the department, I offer our sincere gratitude.”

A FedEx cargo plane stocked with 110,000 pounds of PPE landed at Manchester Airport, the third such shipment to arrive in the state. “It is a tribute to our state that we were more aggressive and proactive in our approach to readiness from the get-go,” said Maj. Gen. David J. Mikolaities, the adjutant general of the New Hampshire Army National Guard, which stood ready to support deployment of the new supplies. “We didn’t wait for the need to occur; we secured the supplies so when and if the demand hits we’d be ready with our PPE distribution.”

The need has been getting stronger. More than 1,300 VA employees have tested positive for COVID-19 according to the VA, and 28 are reported to have died. The cases span 114 VA facilities, but with infections affecting less than 1% of the VA health care workforce, the rate is lower at VA than at several large health care systems, including a 4.4% infection rate at University of Washington Medicine and 2.1% of the Detroit-based Henry Ford Health System.

VA nurses and other hospital employees had been warning for weeks that they did not have enough protective gear. Although VA officials denied this, an April 16 memo sent to network directors by the VA's deputy under secretary for health for operations and management indicated the agency was implementing conservation procedures to stretch supplies.

According to The Washington Post, some of those conservation measures were necessary because FEMA had diverted millions of masks and other PPE that VA had ordered away from the department. In a Post interview, Richard Stone, MD, VHA Executive in Charge, acknowledged that he’d been forced to move to “austerity levels” at some hospitals. (At some facilities, VA employees were provided with one surgical mask per week and N95s were reportedly nearly impossible to find.)

Stone said FEMA had directed vendors with equipment on order from VA to instead send it to FEMA to replenish the government’s rapidly depleting emergency stockpile: “I had 5 million masks incoming that disappeared.” At the time, Stone told the Post, the VA’s four-week supply of equipment was almost gone, and the system was burning through about 200,000 masks in a day. The supply system was responding to FEMA, he said. “I couldn’t tell you when my next delivery was coming in.”

According to a recent ProPublica report, the VA has tried other means to acquire PPE, with limited success. The VA contracted to pay $34.5 million for 6 million N95 respirators, a 350% markup on the normal cost of the masks. Unfortunately, even at that price, the contractor received higher bids for the masks and the VA ended up cancelling the contract.

In an effort to reassure veterans and employees, the VA issued a press release insisting that it had stable and “sufficient” supplies on May 13. According to the release, the VA had on hand “the capacity to take in 12,215 critical and non-critical patients,” and its occupancy rates “remain steady at 35-40% nationwide in both acute care and intensive care units (ICUs).” The release also asserted that the “VA’s stock of medical supplies remains robust with millions of N95 masks on hand,” and 1,943 ICU ventilators.

No one really knows how long the COVID-19 pandemic will endure, and it’s highly likely personal protective equipment (PPE) will be a pressing priority for months to come. Ensuring supplies has become a creative endeavor, with new partnerships forming to fill gaps.

The US Department of Defense (DoD), for instance, has signed a $126 million contract with 3M to produce 26 million N95 masks per month, starting in October, according to DoD spokesperson Lt. Col. Mike Andrews. 3M will expedite design, procurement, production facilities, and equipment to increase respirator production by at least 312 million annually within the next 12 months. The company is ramping up: It has already placed orders for raw material and 2 new N95 manufacturing lines, in addition to beginning initial production in Wisconsin and expanding a facility in South Dakota.

The project, funded through the CARES Act, is spearheaded by the Joint Acquisition Task Force, which serves as the DoD’s overarching framework for acquisition support.

The US Department of Veterans Affairs (VA) also has a new procurement partner: New Hampshire. The state’s leadership, community business leaders and the VA Secretary’s Center for Strategic Partnerships secured millions of masks for VA workforce nationwide.

“Once again, New Hampshire stands out as a leader in our nation for its collaborative nature benefiting veterans,” said Acting VA Deputy Secretary Pamela Powers. “Governor Sununu and Dean Kamen [a New Hampshire-based inventor] made it possible for VA to purchase 4.5 million masks…. Having these additional resources is truly incredible and on behalf of the department, I offer our sincere gratitude.”

A FedEx cargo plane stocked with 110,000 pounds of PPE landed at Manchester Airport, the third such shipment to arrive in the state. “It is a tribute to our state that we were more aggressive and proactive in our approach to readiness from the get-go,” said Maj. Gen. David J. Mikolaities, the adjutant general of the New Hampshire Army National Guard, which stood ready to support deployment of the new supplies. “We didn’t wait for the need to occur; we secured the supplies so when and if the demand hits we’d be ready with our PPE distribution.”

The need has been getting stronger. More than 1,300 VA employees have tested positive for COVID-19 according to the VA, and 28 are reported to have died. The cases span 114 VA facilities, but with infections affecting less than 1% of the VA health care workforce, the rate is lower at VA than at several large health care systems, including a 4.4% infection rate at University of Washington Medicine and 2.1% of the Detroit-based Henry Ford Health System.

VA nurses and other hospital employees had been warning for weeks that they did not have enough protective gear. Although VA officials denied this, an April 16 memo sent to network directors by the VA's deputy under secretary for health for operations and management indicated the agency was implementing conservation procedures to stretch supplies.

According to The Washington Post, some of those conservation measures were necessary because FEMA had diverted millions of masks and other PPE that VA had ordered away from the department. In a Post interview, Richard Stone, MD, VHA Executive in Charge, acknowledged that he’d been forced to move to “austerity levels” at some hospitals. (At some facilities, VA employees were provided with one surgical mask per week and N95s were reportedly nearly impossible to find.)

Stone said FEMA had directed vendors with equipment on order from VA to instead send it to FEMA to replenish the government’s rapidly depleting emergency stockpile: “I had 5 million masks incoming that disappeared.” At the time, Stone told the Post, the VA’s four-week supply of equipment was almost gone, and the system was burning through about 200,000 masks in a day. The supply system was responding to FEMA, he said. “I couldn’t tell you when my next delivery was coming in.”

According to a recent ProPublica report, the VA has tried other means to acquire PPE, with limited success. The VA contracted to pay $34.5 million for 6 million N95 respirators, a 350% markup on the normal cost of the masks. Unfortunately, even at that price, the contractor received higher bids for the masks and the VA ended up cancelling the contract.

In an effort to reassure veterans and employees, the VA issued a press release insisting that it had stable and “sufficient” supplies on May 13. According to the release, the VA had on hand “the capacity to take in 12,215 critical and non-critical patients,” and its occupancy rates “remain steady at 35-40% nationwide in both acute care and intensive care units (ICUs).” The release also asserted that the “VA’s stock of medical supplies remains robust with millions of N95 masks on hand,” and 1,943 ICU ventilators.

Traditionally at this time of year, everyone working in cancer turns their attention toward Chicago, and 40,000 or so travel to the city for the annual meeting of the American Society of Clinical Oncology (ASCO).

Not this year.

The McCormick Place convention center has been converted to a field hospital to cope with the ongoing COVID-19 pandemic. The cavernous meeting halls have been filled with makeshift wards with 750 acute care beds, as shown in a tweet from Toni Choueiri, MD, chief of genitourinary oncology at the Dana Farber Cancer Center in Boston.

But the annual meeting is still going ahead, having been transferred online.

“We have to remember that even though there’s a pandemic going on and people are dying every day from coronavirus, people are still dying every day from cancer,” Richard Schilsky, MD, PhD, chief medical officer at ASCO, told Medscape Medical News.

“This pandemic will end, but cancer will continue, and we need to be able to continue to get the most cutting edge scientific results out there to our members and our constituents so they can act on those results on behalf of their patients,” he said.

The ASCO Virtual Scientific Program will take place over the weekend of May 30-31.

“We’re certainly hoping that we’re going to deliver a program that features all of the most important science that would have been presented in person in Chicago,” Schilsky commented in an interview.

Most of the presentations will be prerecorded and then streamed, which “we hope will mitigate any of the technical glitches that could come from trying to do a live broadcast of the meeting,” he said.

There will be 250 oral and 2500 poster presentations in 24 disease-based and specialty tracks.

The majority of the abstracts will be released online on May 13. The majority of the on-demand content will be released on May 29. Some of the abstracts will be highlighted at ASCO press briefings and released on those two dates.

But some of the material will be made available only on the weekend of the meeting. The opening session, plenaries featuring late-breaking abstracts, special highlights sessions, and other clinical science symposia will be broadcast on Saturday, May 30, and Sunday, May 31 (the schedule for the weekend program is available on the ASCO meeting website).

Among the plenary presentations are some clinical results that are likely to change practice immediately, Schilsky predicted. These include data to be presented in the following abstracts:

• Abstract LBA4 on the KEYNOTE-177 study comparing immunotherapy using pembrolizumab (Keytruda, Merck & Co) with chemotherapy in patients with metastatic colorectal cancer whose tumors show microsatellite instability or mismatch repair deficiency;
• Abstract LBA5 on the ADAURA study exploring osimertinib (Tagrisso, AstraZeneca) as adjuvant therapy after complete tumor reseaction in patients with early-stage non–small cell lung cancer whose tumors are EGFR mutation positive;
• Abstract LBA1 on the JAVELIN Bladder 100 study exploring maintenance avelumab (Bavencio, Merck and Pfizer) with best supportive care after platinum-based first-line chemotherapy in patients with advanced urothelial carcinoma.

However, some of the material that would have been part of the annual meeting, which includes mostly educational sessions and invited talks, has been moved to another event, the ASCO Educational Program, to be held in August 2020.

“So I suppose, in the grand scheme of things, the meeting is going to be compressed a little bit,” Schilsky commented. “Obviously, we can’t deliver all the interactions that happen in the hallways and everywhere else at the meeting that really gives so much energy to the meeting, but, at this moment in our history, probably getting the science out there is what’s most important.”
 

Virtual exhibition hall

There will also be a virtual exhibition hall, which will open on May 29.

“Just as there is a typical exhibit hall in the convention center,” Schilsky commented, most of the companies that were planning to be in Chicago have “now transitioned to creating a virtual booth that people who are participating in the virtual meeting can visit.

“I don’t know exactly how each company is going to use their time and their virtual space, and that’s part of the whole learning process here to see how this whole experiment is going to work out,” he added.

Unlike some of the other conferences that have gone virtual, in which access has been made available to everyone for free, registration is still required for the ASCO meeting. But the society notes that the registration fee has been discounted for nonmembers and has been waived for ASCO members. Also, the fee covers both the Virtual Scientific Program in May and the ASCO Educational Program in August.

Registrants will have access to video and slide presentations, as well as discussant commentaries, for 180 days.

The article first appeared on Medscape.com.

Traditionally at this time of year, everyone working in cancer turns their attention toward Chicago, and 40,000 or so travel to the city for the annual meeting of the American Society of Clinical Oncology (ASCO).

Not this year.

The McCormick Place convention center has been converted to a field hospital to cope with the ongoing COVID-19 pandemic. The cavernous meeting halls have been filled with makeshift wards with 750 acute care beds, as shown in a tweet from Toni Choueiri, MD, chief of genitourinary oncology at the Dana Farber Cancer Center in Boston.

But the annual meeting is still going ahead, having been transferred online.

“We have to remember that even though there’s a pandemic going on and people are dying every day from coronavirus, people are still dying every day from cancer,” Richard Schilsky, MD, PhD, chief medical officer at ASCO, told Medscape Medical News.

“This pandemic will end, but cancer will continue, and we need to be able to continue to get the most cutting edge scientific results out there to our members and our constituents so they can act on those results on behalf of their patients,” he said.

The ASCO Virtual Scientific Program will take place over the weekend of May 30-31.

“We’re certainly hoping that we’re going to deliver a program that features all of the most important science that would have been presented in person in Chicago,” Schilsky commented in an interview.

Most of the presentations will be prerecorded and then streamed, which “we hope will mitigate any of the technical glitches that could come from trying to do a live broadcast of the meeting,” he said.

There will be 250 oral and 2500 poster presentations in 24 disease-based and specialty tracks.

The majority of the abstracts will be released online on May 13. The majority of the on-demand content will be released on May 29. Some of the abstracts will be highlighted at ASCO press briefings and released on those two dates.

But some of the material will be made available only on the weekend of the meeting. The opening session, plenaries featuring late-breaking abstracts, special highlights sessions, and other clinical science symposia will be broadcast on Saturday, May 30, and Sunday, May 31 (the schedule for the weekend program is available on the ASCO meeting website).

Among the plenary presentations are some clinical results that are likely to change practice immediately, Schilsky predicted. These include data to be presented in the following abstracts:

• Abstract LBA4 on the KEYNOTE-177 study comparing immunotherapy using pembrolizumab (Keytruda, Merck & Co) with chemotherapy in patients with metastatic colorectal cancer whose tumors show microsatellite instability or mismatch repair deficiency;
• Abstract LBA5 on the ADAURA study exploring osimertinib (Tagrisso, AstraZeneca) as adjuvant therapy after complete tumor reseaction in patients with early-stage non–small cell lung cancer whose tumors are EGFR mutation positive;
• Abstract LBA1 on the JAVELIN Bladder 100 study exploring maintenance avelumab (Bavencio, Merck and Pfizer) with best supportive care after platinum-based first-line chemotherapy in patients with advanced urothelial carcinoma.

However, some of the material that would have been part of the annual meeting, which includes mostly educational sessions and invited talks, has been moved to another event, the ASCO Educational Program, to be held in August 2020.

“So I suppose, in the grand scheme of things, the meeting is going to be compressed a little bit,” Schilsky commented. “Obviously, we can’t deliver all the interactions that happen in the hallways and everywhere else at the meeting that really gives so much energy to the meeting, but, at this moment in our history, probably getting the science out there is what’s most important.”
 

Virtual exhibition hall

There will also be a virtual exhibition hall, which will open on May 29.

“Just as there is a typical exhibit hall in the convention center,” Schilsky commented, most of the companies that were planning to be in Chicago have “now transitioned to creating a virtual booth that people who are participating in the virtual meeting can visit.

“I don’t know exactly how each company is going to use their time and their virtual space, and that’s part of the whole learning process here to see how this whole experiment is going to work out,” he added.

Unlike some of the other conferences that have gone virtual, in which access has been made available to everyone for free, registration is still required for the ASCO meeting. But the society notes that the registration fee has been discounted for nonmembers and has been waived for ASCO members. Also, the fee covers both the Virtual Scientific Program in May and the ASCO Educational Program in August.

Registrants will have access to video and slide presentations, as well as discussant commentaries, for 180 days.

The article first appeared on Medscape.com.

Traditionally at this time of year, everyone working in cancer turns their attention toward Chicago, and 40,000 or so travel to the city for the annual meeting of the American Society of Clinical Oncology (ASCO).

Not this year.

The McCormick Place convention center has been converted to a field hospital to cope with the ongoing COVID-19 pandemic. The cavernous meeting halls have been filled with makeshift wards with 750 acute care beds, as shown in a tweet from Toni Choueiri, MD, chief of genitourinary oncology at the Dana Farber Cancer Center in Boston.

But the annual meeting is still going ahead, having been transferred online.

“We have to remember that even though there’s a pandemic going on and people are dying every day from coronavirus, people are still dying every day from cancer,” Richard Schilsky, MD, PhD, chief medical officer at ASCO, told Medscape Medical News.

“This pandemic will end, but cancer will continue, and we need to be able to continue to get the most cutting edge scientific results out there to our members and our constituents so they can act on those results on behalf of their patients,” he said.

The ASCO Virtual Scientific Program will take place over the weekend of May 30-31.

“We’re certainly hoping that we’re going to deliver a program that features all of the most important science that would have been presented in person in Chicago,” Schilsky commented in an interview.

Most of the presentations will be prerecorded and then streamed, which “we hope will mitigate any of the technical glitches that could come from trying to do a live broadcast of the meeting,” he said.

There will be 250 oral and 2500 poster presentations in 24 disease-based and specialty tracks.

The majority of the abstracts will be released online on May 13. The majority of the on-demand content will be released on May 29. Some of the abstracts will be highlighted at ASCO press briefings and released on those two dates.

But some of the material will be made available only on the weekend of the meeting. The opening session, plenaries featuring late-breaking abstracts, special highlights sessions, and other clinical science symposia will be broadcast on Saturday, May 30, and Sunday, May 31 (the schedule for the weekend program is available on the ASCO meeting website).

Among the plenary presentations are some clinical results that are likely to change practice immediately, Schilsky predicted. These include data to be presented in the following abstracts:

• Abstract LBA4 on the KEYNOTE-177 study comparing immunotherapy using pembrolizumab (Keytruda, Merck & Co) with chemotherapy in patients with metastatic colorectal cancer whose tumors show microsatellite instability or mismatch repair deficiency;
• Abstract LBA5 on the ADAURA study exploring osimertinib (Tagrisso, AstraZeneca) as adjuvant therapy after complete tumor reseaction in patients with early-stage non–small cell lung cancer whose tumors are EGFR mutation positive;
• Abstract LBA1 on the JAVELIN Bladder 100 study exploring maintenance avelumab (Bavencio, Merck and Pfizer) with best supportive care after platinum-based first-line chemotherapy in patients with advanced urothelial carcinoma.

However, some of the material that would have been part of the annual meeting, which includes mostly educational sessions and invited talks, has been moved to another event, the ASCO Educational Program, to be held in August 2020.

“So I suppose, in the grand scheme of things, the meeting is going to be compressed a little bit,” Schilsky commented. “Obviously, we can’t deliver all the interactions that happen in the hallways and everywhere else at the meeting that really gives so much energy to the meeting, but, at this moment in our history, probably getting the science out there is what’s most important.”
 

Virtual exhibition hall

There will also be a virtual exhibition hall, which will open on May 29.

“Just as there is a typical exhibit hall in the convention center,” Schilsky commented, most of the companies that were planning to be in Chicago have “now transitioned to creating a virtual booth that people who are participating in the virtual meeting can visit.

“I don’t know exactly how each company is going to use their time and their virtual space, and that’s part of the whole learning process here to see how this whole experiment is going to work out,” he added.

Unlike some of the other conferences that have gone virtual, in which access has been made available to everyone for free, registration is still required for the ASCO meeting. But the society notes that the registration fee has been discounted for nonmembers and has been waived for ASCO members. Also, the fee covers both the Virtual Scientific Program in May and the ASCO Educational Program in August.

Registrants will have access to video and slide presentations, as well as discussant commentaries, for 180 days.

The article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

The autologous tumor cell vaccine gemogenovatucel-T (Vigil Ovarian) is well tolerated as maintenance therapy in stage III-IV ovarian cancer patients and may improve relapse-free survival, particularly in BRCA wild-type disease, according to findings from the ongoing VITAL study.

In patients with and without BRCA1/2 mutations, the median relapse-free survival was longer with gemogenovatucel-T maintenance than with placebo, but the difference did not reach statistical significance (P = .065).

However, among patients with wild-type BRCA, the median relapse-free survival was significantly longer with gemogenovatucel-T (P = .0007).

Rodney P. Rocconi, MD, of the Mitchell Cancer Institute at University of South Alabama, Mobile, reported these results in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancers. The meeting was canceled because of the COVID-19 pandemic. Some data have been updated from the abstract.
 

Study rationale

Gemogenovatucel-T (formerly called FANG) is an autologous tumor cell vaccine transfected with a plasmid encoding granulocyte-macrophage colony–stimulating factor and a novel bifunctional short hairpin interfering RNA targeting furin convertase.

“In the era of personalized, targeted medicine, I think this is about as personalized as you can get, this type of vaccine,” Dr. Rocconi said. “Essentially, we harvest patients’ own cancer cells and create a vaccine that is targeted to the antigens on their cells so that it recognizes only that patient’s cancer.”

The vaccine also helps recruit immune cells to the area and has a very limited off-target effect, Dr. Rocconi added.

He noted that gemogenovatucel-T previously demonstrated promising efficacy and limited side effects in a phase 1 study that included patients with advanced ovarian cancer (Mol Ther. 2012 Mar;20[3]:679-86).

“So we thought that, in ovarian cancer, as a maintenance therapy, it made a lot of sense,” Dr. Rocconi said, noting that the overall prognosis for advanced epithelial ovarian cancer remains limited.
 

Treatment and toxicity

Dr. Rocconi and colleagues reported data on 91 patients in the VITAL study. The patients had achieved a complete response after frontline surgery and chemotherapy, and they were randomized to maintenance with gemogenovatucel-T or placebo.

Patients had a median time from surgery to randomization of 208.5 days in the gemogenovatucel-T group and 200 days in the control group. The patients were treated with 1 x 10⁷ cells/mL of gemogenovatucel-T or placebo intradermally once a month for up to 12 doses.

Gemogenovatucel-T was well tolerated. No added overall toxicity was noted in the gemogenovatucel-T group versus the control group, and no grade 4/5 toxicities were observed, Dr. Rocconi said. Grade 2/3 toxic events were observed in 8% of patients in the gemogenovatucel-T group, compared with 18% in the control group. The most common events were nausea and musculoskeletal pain in the gemogenovatucel-T group, and were bone pain and fatigue in the control group.
 

Relapse-free and overall survival

In the entire cohort, the median relapse-free survival was longer with gemogenovatucel-T maintenance – 12.6 months versus 8.4 months with placebo (hazard ratio, 0.69) – but the difference did not reach statistical significance (P = .065).

However, in the 67 patients with wild-type BRCA, the median relapse-free survival was 19.4 months with gemogenovatucel-T and 14.8 months with placebo, a statistically significant difference (HR, 0.459; P = .0007).

The median overall survival was not reached in the BRCA wild-type patients treated with gemogenovatucel-T, and it was 41.4 months from the time of randomization in those who received placebo (HR, 0.417; P = .02).

No benefit was seen with gemogenovatucel-T in patients with known BRCA1/2 mutations, Dr. Rocconi said.
 

‘Encouraging’ results

The overall improvement in the gemogenovatucel-T group was encouraging, particularly in a maintenance-type trial, Dr. Rocconi said. He noted that prior treatments for maintenance have received approval based on shorter survival gains, and the finding of particular benefit in BRCA wild-type disease could have important implications for a population that usually has lesser benefit from treatments, compared with patients who have BRCA mutations.

“So this result is very unique,” Dr. Rocconi said, explaining that about 85% of ovarian cancer patients have BRCA wild-type disease; with this treatment, patients with wild-type BRCA may achieve similar survival rates as those seen in BRCA-mutant disease.

“I think, in general, immunotherapy has been somewhat disappointing in ovarian cancer, so to have a targeted vaccine work in ovarian cancer, just broadly ... is pretty noteworthy,” he said. “We’re really excited, obviously, about the overall success we’ve seen for all patients, but most importantly in those with BRCA wild type. This is a pretty marked significance in recurrence-free intervals and overall survival, and we’re definitely pleased with that.”
 

Next steps

The findings from this trial have been submitted for publication, and efforts are underway to determine next steps through communication with the Food and Drug Administration, Dr. Rocconi said.

Additionally, other studies are underway to assess gemogenovatucel-T in patients who fall in “the middle ground” – that is, patients who have BRCA wild-type disease but have “some homologous recombination deficiency where the tumor itself might be BRCA deficient or have some other type of deficiency,” Dr. Rocconi explained.

“So we’re trying to tease out specifically what is going on across all the different variations of ovarian cancer patients, and also looking for potential biomarkers for predicting response,” he said. “What we would like to see is a companion test where we’re able to predict which patients can really respond and do best with this technology, and, that way, we know how to stratify patients most appropriately.”

The current trial was sponsored by Gradalis. Dr. Rocconi disclosed relationships with Gradalis, Genentech, Clovis, and Johnson & Johnson.

[email protected]

SOURCE: Rocconi RP et al. SGO 2020, Abstract LBA7.

The autologous tumor cell vaccine gemogenovatucel-T (Vigil Ovarian) is well tolerated as maintenance therapy in stage III-IV ovarian cancer patients and may improve relapse-free survival, particularly in BRCA wild-type disease, according to findings from the ongoing VITAL study.

In patients with and without BRCA1/2 mutations, the median relapse-free survival was longer with gemogenovatucel-T maintenance than with placebo, but the difference did not reach statistical significance (P = .065).

However, among patients with wild-type BRCA, the median relapse-free survival was significantly longer with gemogenovatucel-T (P = .0007).

Rodney P. Rocconi, MD, of the Mitchell Cancer Institute at University of South Alabama, Mobile, reported these results in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancers. The meeting was canceled because of the COVID-19 pandemic. Some data have been updated from the abstract.
 

Study rationale

Gemogenovatucel-T (formerly called FANG) is an autologous tumor cell vaccine transfected with a plasmid encoding granulocyte-macrophage colony–stimulating factor and a novel bifunctional short hairpin interfering RNA targeting furin convertase.

“In the era of personalized, targeted medicine, I think this is about as personalized as you can get, this type of vaccine,” Dr. Rocconi said. “Essentially, we harvest patients’ own cancer cells and create a vaccine that is targeted to the antigens on their cells so that it recognizes only that patient’s cancer.”

The vaccine also helps recruit immune cells to the area and has a very limited off-target effect, Dr. Rocconi added.

He noted that gemogenovatucel-T previously demonstrated promising efficacy and limited side effects in a phase 1 study that included patients with advanced ovarian cancer (Mol Ther. 2012 Mar;20[3]:679-86).

“So we thought that, in ovarian cancer, as a maintenance therapy, it made a lot of sense,” Dr. Rocconi said, noting that the overall prognosis for advanced epithelial ovarian cancer remains limited.
 

Treatment and toxicity

Dr. Rocconi and colleagues reported data on 91 patients in the VITAL study. The patients had achieved a complete response after frontline surgery and chemotherapy, and they were randomized to maintenance with gemogenovatucel-T or placebo.

Patients had a median time from surgery to randomization of 208.5 days in the gemogenovatucel-T group and 200 days in the control group. The patients were treated with 1 x 10⁷ cells/mL of gemogenovatucel-T or placebo intradermally once a month for up to 12 doses.

Gemogenovatucel-T was well tolerated. No added overall toxicity was noted in the gemogenovatucel-T group versus the control group, and no grade 4/5 toxicities were observed, Dr. Rocconi said. Grade 2/3 toxic events were observed in 8% of patients in the gemogenovatucel-T group, compared with 18% in the control group. The most common events were nausea and musculoskeletal pain in the gemogenovatucel-T group, and were bone pain and fatigue in the control group.
 

Relapse-free and overall survival

In the entire cohort, the median relapse-free survival was longer with gemogenovatucel-T maintenance – 12.6 months versus 8.4 months with placebo (hazard ratio, 0.69) – but the difference did not reach statistical significance (P = .065).

However, in the 67 patients with wild-type BRCA, the median relapse-free survival was 19.4 months with gemogenovatucel-T and 14.8 months with placebo, a statistically significant difference (HR, 0.459; P = .0007).

The median overall survival was not reached in the BRCA wild-type patients treated with gemogenovatucel-T, and it was 41.4 months from the time of randomization in those who received placebo (HR, 0.417; P = .02).

No benefit was seen with gemogenovatucel-T in patients with known BRCA1/2 mutations, Dr. Rocconi said.
 

‘Encouraging’ results

The overall improvement in the gemogenovatucel-T group was encouraging, particularly in a maintenance-type trial, Dr. Rocconi said. He noted that prior treatments for maintenance have received approval based on shorter survival gains, and the finding of particular benefit in BRCA wild-type disease could have important implications for a population that usually has lesser benefit from treatments, compared with patients who have BRCA mutations.

“So this result is very unique,” Dr. Rocconi said, explaining that about 85% of ovarian cancer patients have BRCA wild-type disease; with this treatment, patients with wild-type BRCA may achieve similar survival rates as those seen in BRCA-mutant disease.

“I think, in general, immunotherapy has been somewhat disappointing in ovarian cancer, so to have a targeted vaccine work in ovarian cancer, just broadly ... is pretty noteworthy,” he said. “We’re really excited, obviously, about the overall success we’ve seen for all patients, but most importantly in those with BRCA wild type. This is a pretty marked significance in recurrence-free intervals and overall survival, and we’re definitely pleased with that.”
 

Next steps

The findings from this trial have been submitted for publication, and efforts are underway to determine next steps through communication with the Food and Drug Administration, Dr. Rocconi said.

Additionally, other studies are underway to assess gemogenovatucel-T in patients who fall in “the middle ground” – that is, patients who have BRCA wild-type disease but have “some homologous recombination deficiency where the tumor itself might be BRCA deficient or have some other type of deficiency,” Dr. Rocconi explained.

“So we’re trying to tease out specifically what is going on across all the different variations of ovarian cancer patients, and also looking for potential biomarkers for predicting response,” he said. “What we would like to see is a companion test where we’re able to predict which patients can really respond and do best with this technology, and, that way, we know how to stratify patients most appropriately.”

The current trial was sponsored by Gradalis. Dr. Rocconi disclosed relationships with Gradalis, Genentech, Clovis, and Johnson & Johnson.

[email protected]

SOURCE: Rocconi RP et al. SGO 2020, Abstract LBA7.

The autologous tumor cell vaccine gemogenovatucel-T (Vigil Ovarian) is well tolerated as maintenance therapy in stage III-IV ovarian cancer patients and may improve relapse-free survival, particularly in BRCA wild-type disease, according to findings from the ongoing VITAL study.

In patients with and without BRCA1/2 mutations, the median relapse-free survival was longer with gemogenovatucel-T maintenance than with placebo, but the difference did not reach statistical significance (P = .065).

However, among patients with wild-type BRCA, the median relapse-free survival was significantly longer with gemogenovatucel-T (P = .0007).

Rodney P. Rocconi, MD, of the Mitchell Cancer Institute at University of South Alabama, Mobile, reported these results in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancers. The meeting was canceled because of the COVID-19 pandemic. Some data have been updated from the abstract.
 

Study rationale

Gemogenovatucel-T (formerly called FANG) is an autologous tumor cell vaccine transfected with a plasmid encoding granulocyte-macrophage colony–stimulating factor and a novel bifunctional short hairpin interfering RNA targeting furin convertase.

“In the era of personalized, targeted medicine, I think this is about as personalized as you can get, this type of vaccine,” Dr. Rocconi said. “Essentially, we harvest patients’ own cancer cells and create a vaccine that is targeted to the antigens on their cells so that it recognizes only that patient’s cancer.”

The vaccine also helps recruit immune cells to the area and has a very limited off-target effect, Dr. Rocconi added.

He noted that gemogenovatucel-T previously demonstrated promising efficacy and limited side effects in a phase 1 study that included patients with advanced ovarian cancer (Mol Ther. 2012 Mar;20[3]:679-86).

“So we thought that, in ovarian cancer, as a maintenance therapy, it made a lot of sense,” Dr. Rocconi said, noting that the overall prognosis for advanced epithelial ovarian cancer remains limited.
 

Treatment and toxicity

Dr. Rocconi and colleagues reported data on 91 patients in the VITAL study. The patients had achieved a complete response after frontline surgery and chemotherapy, and they were randomized to maintenance with gemogenovatucel-T or placebo.

Patients had a median time from surgery to randomization of 208.5 days in the gemogenovatucel-T group and 200 days in the control group. The patients were treated with 1 x 10⁷ cells/mL of gemogenovatucel-T or placebo intradermally once a month for up to 12 doses.

Gemogenovatucel-T was well tolerated. No added overall toxicity was noted in the gemogenovatucel-T group versus the control group, and no grade 4/5 toxicities were observed, Dr. Rocconi said. Grade 2/3 toxic events were observed in 8% of patients in the gemogenovatucel-T group, compared with 18% in the control group. The most common events were nausea and musculoskeletal pain in the gemogenovatucel-T group, and were bone pain and fatigue in the control group.
 

Relapse-free and overall survival

In the entire cohort, the median relapse-free survival was longer with gemogenovatucel-T maintenance – 12.6 months versus 8.4 months with placebo (hazard ratio, 0.69) – but the difference did not reach statistical significance (P = .065).

However, in the 67 patients with wild-type BRCA, the median relapse-free survival was 19.4 months with gemogenovatucel-T and 14.8 months with placebo, a statistically significant difference (HR, 0.459; P = .0007).

The median overall survival was not reached in the BRCA wild-type patients treated with gemogenovatucel-T, and it was 41.4 months from the time of randomization in those who received placebo (HR, 0.417; P = .02).

No benefit was seen with gemogenovatucel-T in patients with known BRCA1/2 mutations, Dr. Rocconi said.
 

‘Encouraging’ results

The overall improvement in the gemogenovatucel-T group was encouraging, particularly in a maintenance-type trial, Dr. Rocconi said. He noted that prior treatments for maintenance have received approval based on shorter survival gains, and the finding of particular benefit in BRCA wild-type disease could have important implications for a population that usually has lesser benefit from treatments, compared with patients who have BRCA mutations.

“So this result is very unique,” Dr. Rocconi said, explaining that about 85% of ovarian cancer patients have BRCA wild-type disease; with this treatment, patients with wild-type BRCA may achieve similar survival rates as those seen in BRCA-mutant disease.

“I think, in general, immunotherapy has been somewhat disappointing in ovarian cancer, so to have a targeted vaccine work in ovarian cancer, just broadly ... is pretty noteworthy,” he said. “We’re really excited, obviously, about the overall success we’ve seen for all patients, but most importantly in those with BRCA wild type. This is a pretty marked significance in recurrence-free intervals and overall survival, and we’re definitely pleased with that.”
 

Next steps

The findings from this trial have been submitted for publication, and efforts are underway to determine next steps through communication with the Food and Drug Administration, Dr. Rocconi said.

Additionally, other studies are underway to assess gemogenovatucel-T in patients who fall in “the middle ground” – that is, patients who have BRCA wild-type disease but have “some homologous recombination deficiency where the tumor itself might be BRCA deficient or have some other type of deficiency,” Dr. Rocconi explained.

“So we’re trying to tease out specifically what is going on across all the different variations of ovarian cancer patients, and also looking for potential biomarkers for predicting response,” he said. “What we would like to see is a companion test where we’re able to predict which patients can really respond and do best with this technology, and, that way, we know how to stratify patients most appropriately.”

The current trial was sponsored by Gradalis. Dr. Rocconi disclosed relationships with Gradalis, Genentech, Clovis, and Johnson & Johnson.

[email protected]

SOURCE: Rocconi RP et al. SGO 2020, Abstract LBA7.

COVID-19 patients with cancer had double the fatality rate of COVID-19 patients without cancer treated in an urban New York hospital system, according to data from a retrospective study.

The case fatality rate was 28% (61/218) among cancer patients with COVID-19 and 14% (149/1,090) among matched noncancer patients with COVID-19 treated during the same time period in the same hospital system.

Vikas Mehta, MD, of Montefiore Medical Center, New York, and colleagues reported these results in Cancer Discovery.

“As New York has emerged as the current epicenter of the pandemic, we sought to investigate the risk posed by COVID-19 to our cancer population,” the authors wrote.

They identified 218 cancer patients treated for COVID-19 in the Montefiore Health System between March 18 and April 8, 2020. Three-quarters of patients had solid tumors, and 25% had hematologic malignancies. Most patients were adults (98.6%), their median age was 69 years (range, 10-92 years), and 58% were men.

In all, 28% of the cancer patients (61/218) died from COVID-19, including 25% (41/164) of those with solid tumors and 37% (20/54) of those with hematologic malignancies.

Deaths by cancer type

Among the 164 patients with solid tumors, case fatality rates were as follows:

• Pancreatic – 67% (2/3)
• Lung – 55% (6/11)
• Colorectal – 38% (8/21)
• Upper gastrointestinal – 38% (3/8)
• Gynecologic – 38% (5/13)
• Skin – 33% (1/3)
• Hepatobiliary – 29% (2/7)
• Bone/soft tissue – 20% (1/5)
• Genitourinary – 15% (7/46)
• Breast – 14% (4/28)
• Neurologic – 13% (1/8)
• Head and neck – 13% (1/8).

None of the three patients with neuroendocrine tumors died.

Among the 54 patients with hematologic malignancies, case fatality rates were as follows:

• Chronic myeloid leukemia – 100% (1/1)
• Hodgkin lymphoma – 60% (3/5)
• Myelodysplastic syndromes – 60% (3/5)
• Multiple myeloma – 38% (5/13)
• Non-Hodgkin lymphoma – 33% (5/15)
• Chronic lymphocytic leukemia – 33% (1/3)
• Myeloproliferative neoplasms – 29% (2/7).

None of the four patients with acute lymphoblastic leukemia died, and there was one patient with acute myeloid leukemia who did not die.

Factors associated with increased mortality

The researchers compared the 218 cancer patients with COVID-19 with 1,090 age- and sex-matched noncancer patients with COVID-19 treated in the Montefiore Health System between March 18 and April 8, 2020.

Case fatality rates in cancer patients with COVID-19 were significantly increased in all age groups, but older age was associated with higher mortality.

“We observed case fatality rates were elevated in all age cohorts in cancer patients and achieved statistical significance in the age groups 45-64 and in patients older than 75 years of age,” the authors reported.

Other factors significantly associated with higher mortality in a multivariable analysis included the presence of multiple comorbidities; the need for ICU support; and increased levels of d-dimer, lactate, and lactate dehydrogenase.

Additional factors, such as socioeconomic and health disparities, may also be significant predictors of mortality, according to the authors. They noted that this cohort largely consisted of patients from a socioeconomically underprivileged community where mortality because of COVID-19 is reportedly higher.
 

Proactive strategies moving forward

“We have been addressing the significant burden of the COVID-19 pandemic on our vulnerable cancer patients through a variety of ways,” said study author Balazs Halmos, MD, of Montefiore Medical Center.

The center set up a separate infusion unit exclusively for COVID-positive patients and established separate inpatient areas. Dr. Halmos and colleagues are also providing telemedicine, virtual supportive care services, telephonic counseling, and bilingual peer-support programs.

“Many questions remain as we continue to establish new practices for our cancer patients,” Dr. Halmos said. “We will find answers to these questions as we continue to focus on adaptation and not acceptance in response to the COVID crisis. Our patients deserve nothing less.”

The Albert Einstein Cancer Center supported this study. The authors reported having no conflicts of interest.

SOURCE: Mehta V et al. Cancer Discov. 2020 May 1. doi: 10.1158/2159-8290.CD-20-0516.

COVID-19 patients with cancer had double the fatality rate of COVID-19 patients without cancer treated in an urban New York hospital system, according to data from a retrospective study.

The case fatality rate was 28% (61/218) among cancer patients with COVID-19 and 14% (149/1,090) among matched noncancer patients with COVID-19 treated during the same time period in the same hospital system.

Vikas Mehta, MD, of Montefiore Medical Center, New York, and colleagues reported these results in Cancer Discovery.

“As New York has emerged as the current epicenter of the pandemic, we sought to investigate the risk posed by COVID-19 to our cancer population,” the authors wrote.

They identified 218 cancer patients treated for COVID-19 in the Montefiore Health System between March 18 and April 8, 2020. Three-quarters of patients had solid tumors, and 25% had hematologic malignancies. Most patients were adults (98.6%), their median age was 69 years (range, 10-92 years), and 58% were men.

In all, 28% of the cancer patients (61/218) died from COVID-19, including 25% (41/164) of those with solid tumors and 37% (20/54) of those with hematologic malignancies.

Deaths by cancer type

Among the 164 patients with solid tumors, case fatality rates were as follows:

• Pancreatic – 67% (2/3)
• Lung – 55% (6/11)
• Colorectal – 38% (8/21)
• Upper gastrointestinal – 38% (3/8)
• Gynecologic – 38% (5/13)
• Skin – 33% (1/3)
• Hepatobiliary – 29% (2/7)
• Bone/soft tissue – 20% (1/5)
• Genitourinary – 15% (7/46)
• Breast – 14% (4/28)
• Neurologic – 13% (1/8)
• Head and neck – 13% (1/8).

None of the three patients with neuroendocrine tumors died.

Among the 54 patients with hematologic malignancies, case fatality rates were as follows:

• Chronic myeloid leukemia – 100% (1/1)
• Hodgkin lymphoma – 60% (3/5)
• Myelodysplastic syndromes – 60% (3/5)
• Multiple myeloma – 38% (5/13)
• Non-Hodgkin lymphoma – 33% (5/15)
• Chronic lymphocytic leukemia – 33% (1/3)
• Myeloproliferative neoplasms – 29% (2/7).

None of the four patients with acute lymphoblastic leukemia died, and there was one patient with acute myeloid leukemia who did not die.

Factors associated with increased mortality

The researchers compared the 218 cancer patients with COVID-19 with 1,090 age- and sex-matched noncancer patients with COVID-19 treated in the Montefiore Health System between March 18 and April 8, 2020.

Case fatality rates in cancer patients with COVID-19 were significantly increased in all age groups, but older age was associated with higher mortality.

“We observed case fatality rates were elevated in all age cohorts in cancer patients and achieved statistical significance in the age groups 45-64 and in patients older than 75 years of age,” the authors reported.

Other factors significantly associated with higher mortality in a multivariable analysis included the presence of multiple comorbidities; the need for ICU support; and increased levels of d-dimer, lactate, and lactate dehydrogenase.

Additional factors, such as socioeconomic and health disparities, may also be significant predictors of mortality, according to the authors. They noted that this cohort largely consisted of patients from a socioeconomically underprivileged community where mortality because of COVID-19 is reportedly higher.
 

Proactive strategies moving forward

“We have been addressing the significant burden of the COVID-19 pandemic on our vulnerable cancer patients through a variety of ways,” said study author Balazs Halmos, MD, of Montefiore Medical Center.

The center set up a separate infusion unit exclusively for COVID-positive patients and established separate inpatient areas. Dr. Halmos and colleagues are also providing telemedicine, virtual supportive care services, telephonic counseling, and bilingual peer-support programs.

“Many questions remain as we continue to establish new practices for our cancer patients,” Dr. Halmos said. “We will find answers to these questions as we continue to focus on adaptation and not acceptance in response to the COVID crisis. Our patients deserve nothing less.”

The Albert Einstein Cancer Center supported this study. The authors reported having no conflicts of interest.

SOURCE: Mehta V et al. Cancer Discov. 2020 May 1. doi: 10.1158/2159-8290.CD-20-0516.

COVID-19 patients with cancer had double the fatality rate of COVID-19 patients without cancer treated in an urban New York hospital system, according to data from a retrospective study.

The case fatality rate was 28% (61/218) among cancer patients with COVID-19 and 14% (149/1,090) among matched noncancer patients with COVID-19 treated during the same time period in the same hospital system.

Vikas Mehta, MD, of Montefiore Medical Center, New York, and colleagues reported these results in Cancer Discovery.

“As New York has emerged as the current epicenter of the pandemic, we sought to investigate the risk posed by COVID-19 to our cancer population,” the authors wrote.

They identified 218 cancer patients treated for COVID-19 in the Montefiore Health System between March 18 and April 8, 2020. Three-quarters of patients had solid tumors, and 25% had hematologic malignancies. Most patients were adults (98.6%), their median age was 69 years (range, 10-92 years), and 58% were men.

In all, 28% of the cancer patients (61/218) died from COVID-19, including 25% (41/164) of those with solid tumors and 37% (20/54) of those with hematologic malignancies.

Deaths by cancer type

Among the 164 patients with solid tumors, case fatality rates were as follows:

• Pancreatic – 67% (2/3)
• Lung – 55% (6/11)
• Colorectal – 38% (8/21)
• Upper gastrointestinal – 38% (3/8)
• Gynecologic – 38% (5/13)
• Skin – 33% (1/3)
• Hepatobiliary – 29% (2/7)
• Bone/soft tissue – 20% (1/5)
• Genitourinary – 15% (7/46)
• Breast – 14% (4/28)
• Neurologic – 13% (1/8)
• Head and neck – 13% (1/8).

None of the three patients with neuroendocrine tumors died.

Among the 54 patients with hematologic malignancies, case fatality rates were as follows:

• Chronic myeloid leukemia – 100% (1/1)
• Hodgkin lymphoma – 60% (3/5)
• Myelodysplastic syndromes – 60% (3/5)
• Multiple myeloma – 38% (5/13)
• Non-Hodgkin lymphoma – 33% (5/15)
• Chronic lymphocytic leukemia – 33% (1/3)
• Myeloproliferative neoplasms – 29% (2/7).

None of the four patients with acute lymphoblastic leukemia died, and there was one patient with acute myeloid leukemia who did not die.

Factors associated with increased mortality

The researchers compared the 218 cancer patients with COVID-19 with 1,090 age- and sex-matched noncancer patients with COVID-19 treated in the Montefiore Health System between March 18 and April 8, 2020.

Case fatality rates in cancer patients with COVID-19 were significantly increased in all age groups, but older age was associated with higher mortality.

“We observed case fatality rates were elevated in all age cohorts in cancer patients and achieved statistical significance in the age groups 45-64 and in patients older than 75 years of age,” the authors reported.

Other factors significantly associated with higher mortality in a multivariable analysis included the presence of multiple comorbidities; the need for ICU support; and increased levels of d-dimer, lactate, and lactate dehydrogenase.

Additional factors, such as socioeconomic and health disparities, may also be significant predictors of mortality, according to the authors. They noted that this cohort largely consisted of patients from a socioeconomically underprivileged community where mortality because of COVID-19 is reportedly higher.
 

Proactive strategies moving forward

“We have been addressing the significant burden of the COVID-19 pandemic on our vulnerable cancer patients through a variety of ways,” said study author Balazs Halmos, MD, of Montefiore Medical Center.

The center set up a separate infusion unit exclusively for COVID-positive patients and established separate inpatient areas. Dr. Halmos and colleagues are also providing telemedicine, virtual supportive care services, telephonic counseling, and bilingual peer-support programs.

“Many questions remain as we continue to establish new practices for our cancer patients,” Dr. Halmos said. “We will find answers to these questions as we continue to focus on adaptation and not acceptance in response to the COVID crisis. Our patients deserve nothing less.”

The Albert Einstein Cancer Center supported this study. The authors reported having no conflicts of interest.

SOURCE: Mehta V et al. Cancer Discov. 2020 May 1. doi: 10.1158/2159-8290.CD-20-0516.