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Cutting amino acids from diet could fight lymphoma
Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.
Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.
The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).
As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.
“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.
He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.
The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).
To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.
The researchers found that Tigar -/- mice on the SG-free diet had significantly better survival than Tigar -/- mice on the control diet (P=0.0451).
The median survival was 50.5 days for Tigar +/+ mice on the control diet, 80 days for Tigar +/+ mice on the SG-free diet, 107 days for Tigar -/- mice on the control diet, and 226 days for Tigar -/- mice on the SG-free diet.
The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.
“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.
“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.” 
Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.
Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.
The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).
As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.
“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.
He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.
The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).
To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.
The researchers found that Tigar -/- mice on the SG-free diet had significantly better survival than Tigar -/- mice on the control diet (P=0.0451).
The median survival was 50.5 days for Tigar +/+ mice on the control diet, 80 days for Tigar +/+ mice on the SG-free diet, 107 days for Tigar -/- mice on the control diet, and 226 days for Tigar -/- mice on the SG-free diet.
The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.
“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.
“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”
Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.
Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.
The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).
As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.
“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.
He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.
The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).
To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.
The researchers found that Tigar -/- mice on the SG-free diet had significantly better survival than Tigar -/- mice on the control diet (P=0.0451).
The median survival was 50.5 days for Tigar +/+ mice on the control diet, 80 days for Tigar +/+ mice on the SG-free diet, 107 days for Tigar -/- mice on the control diet, and 226 days for Tigar -/- mice on the SG-free diet.
The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.
“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.
“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”
CAR T-cell therapy receives breakthrough designation
The US Food and Drug Administration (FDA) has granted another breakthrough therapy designation to CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor (CAR) T-cell therapy.
CTL019 now has breakthrough designation as a treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have failed 2 or more prior therapies.
The FDA previously granted CTL019 breakthrough designation as a treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients.
Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if those medicines have demonstrated substantial improvement over available therapies.
The breakthrough designation for CTL019 in DLBCL is based on data from the phase 2 JULIET trial (NCT02445248), in which researchers are evaluating the efficacy and safety of CTL019 in adults with relapsed/refractory DLBCL.
Findings from JULIET are expected to be presented at an upcoming medical meeting.
About CTL019
CTL019 consists of autologous T cells expressing a CD19-specific CAR. The therapy was first developed by the University of Pennsylvania.
In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including CTL019. Novartis holds the worldwide rights to CARs developed through the collaboration.
According to Novartis, regulatory submissions for CTL019 in the treatment of relapsed/refractory DLBCL are expected to be filed by the end of the year.
The company has already filed a biologics license application with the FDA for CTL019 as a treatment for patients with relapsed/refractory B-cell ALL. The FDA granted that application priority review.
The US Food and Drug Administration (FDA) has granted another breakthrough therapy designation to CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor (CAR) T-cell therapy.
CTL019 now has breakthrough designation as a treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have failed 2 or more prior therapies.
The FDA previously granted CTL019 breakthrough designation as a treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients.
Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if those medicines have demonstrated substantial improvement over available therapies.
The breakthrough designation for CTL019 in DLBCL is based on data from the phase 2 JULIET trial (NCT02445248), in which researchers are evaluating the efficacy and safety of CTL019 in adults with relapsed/refractory DLBCL.
Findings from JULIET are expected to be presented at an upcoming medical meeting.
About CTL019
CTL019 consists of autologous T cells expressing a CD19-specific CAR. The therapy was first developed by the University of Pennsylvania.
In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including CTL019. Novartis holds the worldwide rights to CARs developed through the collaboration.
According to Novartis, regulatory submissions for CTL019 in the treatment of relapsed/refractory DLBCL are expected to be filed by the end of the year.
The company has already filed a biologics license application with the FDA for CTL019 as a treatment for patients with relapsed/refractory B-cell ALL. The FDA granted that application priority review.
The US Food and Drug Administration (FDA) has granted another breakthrough therapy designation to CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor (CAR) T-cell therapy.
CTL019 now has breakthrough designation as a treatment for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have failed 2 or more prior therapies.
The FDA previously granted CTL019 breakthrough designation as a treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients.
Breakthrough designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if those medicines have demonstrated substantial improvement over available therapies.
The breakthrough designation for CTL019 in DLBCL is based on data from the phase 2 JULIET trial (NCT02445248), in which researchers are evaluating the efficacy and safety of CTL019 in adults with relapsed/refractory DLBCL.
Findings from JULIET are expected to be presented at an upcoming medical meeting.
About CTL019
CTL019 consists of autologous T cells expressing a CD19-specific CAR. The therapy was first developed by the University of Pennsylvania.
In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including CTL019. Novartis holds the worldwide rights to CARs developed through the collaboration.
According to Novartis, regulatory submissions for CTL019 in the treatment of relapsed/refractory DLBCL are expected to be filed by the end of the year.
The company has already filed a biologics license application with the FDA for CTL019 as a treatment for patients with relapsed/refractory B-cell ALL. The FDA granted that application priority review.
Inhibitor exhibits activity against hematologic malignancies
A dual kinase inhibitor is active against a range of hematologic malignancies, according to preclinical research.
Investigators found that ASN002, a SYK/JAK inhibitor, exhibited “potent” antiproliferative activity in leukemia, lymphoma, and myeloma cell lines.
ASN002 also inhibited tumor growth in mouse models of these malignancies and proved active against ibrutinib-resistant diffuse large B-cell lymphoma (DLBCL).
The investigators presented these results at the AACR Annual Meeting 2017 (abstract 4204).
The work was conducted by employees of Asana BioSciences, the company developing ASN002.
The investigators tested ASN002 in 178 cell lines and found the drug exhibited “strong antiproliferative activity” in a range of hematologic cancer cell lines, including:
- Leukemia—HEL31, HL60, Jurkat, MOLM-13, and MOLM-16
- Lymphoma—KARPAS-299, OCI-LY10, OCI-LY-19, Pfeiffer, Raji, Ramos, SU-DHL-1, SU-DHL-6, and SU-DHL-10
- Myeloma—H929, JJN3, OPM2, and U266.
In addition, ASN002 was active against ibrutinib-resistant clones derived from the DLBCL cell line SU-DHL-6.
In a SU-DHL-6 xenograft model, the combination of ASN002 and ibrutinib was more effective than either compound alone.
The investigators also found that ASN002 alone demonstrated “strong tumor growth inhibition” in mouse models of DLBCL (Pfeiffer and SU-DHL-6), myeloma (H929), and erythroleukemia (HEL).
The team pointed out that ASN002 is currently under investigation in a phase 1/2 study of patients with B-cell lymphomas (DLBCL, mantle cell lymphoma, and follicular lymphoma) as well as solid tumors.
The investigators said that, to date, ASN002 has been well tolerated and has shown encouraging early evidence of clinical activity and symptomatic benefit in the lymphoma patients.
A dual kinase inhibitor is active against a range of hematologic malignancies, according to preclinical research.
Investigators found that ASN002, a SYK/JAK inhibitor, exhibited “potent” antiproliferative activity in leukemia, lymphoma, and myeloma cell lines.
ASN002 also inhibited tumor growth in mouse models of these malignancies and proved active against ibrutinib-resistant diffuse large B-cell lymphoma (DLBCL).
The investigators presented these results at the AACR Annual Meeting 2017 (abstract 4204).
The work was conducted by employees of Asana BioSciences, the company developing ASN002.
The investigators tested ASN002 in 178 cell lines and found the drug exhibited “strong antiproliferative activity” in a range of hematologic cancer cell lines, including:
- Leukemia—HEL31, HL60, Jurkat, MOLM-13, and MOLM-16
- Lymphoma—KARPAS-299, OCI-LY10, OCI-LY-19, Pfeiffer, Raji, Ramos, SU-DHL-1, SU-DHL-6, and SU-DHL-10
- Myeloma—H929, JJN3, OPM2, and U266.
In addition, ASN002 was active against ibrutinib-resistant clones derived from the DLBCL cell line SU-DHL-6.
In a SU-DHL-6 xenograft model, the combination of ASN002 and ibrutinib was more effective than either compound alone.
The investigators also found that ASN002 alone demonstrated “strong tumor growth inhibition” in mouse models of DLBCL (Pfeiffer and SU-DHL-6), myeloma (H929), and erythroleukemia (HEL).
The team pointed out that ASN002 is currently under investigation in a phase 1/2 study of patients with B-cell lymphomas (DLBCL, mantle cell lymphoma, and follicular lymphoma) as well as solid tumors.
The investigators said that, to date, ASN002 has been well tolerated and has shown encouraging early evidence of clinical activity and symptomatic benefit in the lymphoma patients.
A dual kinase inhibitor is active against a range of hematologic malignancies, according to preclinical research.
Investigators found that ASN002, a SYK/JAK inhibitor, exhibited “potent” antiproliferative activity in leukemia, lymphoma, and myeloma cell lines.
ASN002 also inhibited tumor growth in mouse models of these malignancies and proved active against ibrutinib-resistant diffuse large B-cell lymphoma (DLBCL).
The investigators presented these results at the AACR Annual Meeting 2017 (abstract 4204).
The work was conducted by employees of Asana BioSciences, the company developing ASN002.
The investigators tested ASN002 in 178 cell lines and found the drug exhibited “strong antiproliferative activity” in a range of hematologic cancer cell lines, including:
- Leukemia—HEL31, HL60, Jurkat, MOLM-13, and MOLM-16
- Lymphoma—KARPAS-299, OCI-LY10, OCI-LY-19, Pfeiffer, Raji, Ramos, SU-DHL-1, SU-DHL-6, and SU-DHL-10
- Myeloma—H929, JJN3, OPM2, and U266.
In addition, ASN002 was active against ibrutinib-resistant clones derived from the DLBCL cell line SU-DHL-6.
In a SU-DHL-6 xenograft model, the combination of ASN002 and ibrutinib was more effective than either compound alone.
The investigators also found that ASN002 alone demonstrated “strong tumor growth inhibition” in mouse models of DLBCL (Pfeiffer and SU-DHL-6), myeloma (H929), and erythroleukemia (HEL).
The team pointed out that ASN002 is currently under investigation in a phase 1/2 study of patients with B-cell lymphomas (DLBCL, mantle cell lymphoma, and follicular lymphoma) as well as solid tumors.
The investigators said that, to date, ASN002 has been well tolerated and has shown encouraging early evidence of clinical activity and symptomatic benefit in the lymphoma patients.
Leukemia, NHL more common in African-born blacks than US-born blacks
The cancer profile of black US immigrants born in sub-Saharan Africa (ABs) differs from that of US-born black individuals (USBs) and varies by region of birth, according to a new study.
For instance, the data showed that ABs who immigrated to the US had a higher incidence of leukemia and non-Hodgkin lymphoma (NHL) than USBs.
And there was a higher incidence of NHL among ABs born in Eastern Africa than among those born in Western Africa.
“Typically, cancer occurrence among blacks in the United States is presented as one homogeneous group, with no breakdown by country or region of birth,” said Ahemdin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia.
“Our study shows that approach masks important potential differences that may be key to guiding cancer prevention programs for African-born black immigrants.”
Dr Jemal and his colleagues described this study in the journal Cancer.
The team reviewed cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER 17) program covering the period from 2000 through 2012.
They calculated age-standardized proportional incidence ratios (PIRs), comparing the frequency of the top 15 cancers in ABs with that of USBs, by sex and region of birth.
ABs had a significantly higher proportion of hematologic malignancies (leukemia and NHL), infection-related cancers (liver, stomach, and Kaposi sarcoma), prostate cancer, and thyroid cancers (in females only), when compared to USBs.
In females, the incidence of NHL was 3.4% in ABs and 2.5% in USBs, with a PIR of 1.19. The incidence of leukemia was 3.0% in ABs and 1.9% in USBs, with a PIR of 1.62.
In males, the incidence of NHL was 5.9% in ABs and 3.0% in USBs, with a PIR of 1.34. The incidence of leukemia was 3.0% in ABs and 2.2% in USBs, with a PIR of 1.40.
The investigators also calculated the PIRs of the 5 most frequent cancers in ABs compared to USBs by region of origin (Western Africa vs Eastern Africa).
For both sexes, the incidence of NHL was 4.0% in ABs born in Western Africa (PIR=1.17) and 5.5% in ABs born in Eastern Africa (PIR=1.44).
Leukemia was not included in this analysis because it was not among the top 5 cancers.
The cancer profile of black US immigrants born in sub-Saharan Africa (ABs) differs from that of US-born black individuals (USBs) and varies by region of birth, according to a new study.
For instance, the data showed that ABs who immigrated to the US had a higher incidence of leukemia and non-Hodgkin lymphoma (NHL) than USBs.
And there was a higher incidence of NHL among ABs born in Eastern Africa than among those born in Western Africa.
“Typically, cancer occurrence among blacks in the United States is presented as one homogeneous group, with no breakdown by country or region of birth,” said Ahemdin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia.
“Our study shows that approach masks important potential differences that may be key to guiding cancer prevention programs for African-born black immigrants.”
Dr Jemal and his colleagues described this study in the journal Cancer.
The team reviewed cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER 17) program covering the period from 2000 through 2012.
They calculated age-standardized proportional incidence ratios (PIRs), comparing the frequency of the top 15 cancers in ABs with that of USBs, by sex and region of birth.
ABs had a significantly higher proportion of hematologic malignancies (leukemia and NHL), infection-related cancers (liver, stomach, and Kaposi sarcoma), prostate cancer, and thyroid cancers (in females only), when compared to USBs.
In females, the incidence of NHL was 3.4% in ABs and 2.5% in USBs, with a PIR of 1.19. The incidence of leukemia was 3.0% in ABs and 1.9% in USBs, with a PIR of 1.62.
In males, the incidence of NHL was 5.9% in ABs and 3.0% in USBs, with a PIR of 1.34. The incidence of leukemia was 3.0% in ABs and 2.2% in USBs, with a PIR of 1.40.
The investigators also calculated the PIRs of the 5 most frequent cancers in ABs compared to USBs by region of origin (Western Africa vs Eastern Africa).
For both sexes, the incidence of NHL was 4.0% in ABs born in Western Africa (PIR=1.17) and 5.5% in ABs born in Eastern Africa (PIR=1.44).
Leukemia was not included in this analysis because it was not among the top 5 cancers.
The cancer profile of black US immigrants born in sub-Saharan Africa (ABs) differs from that of US-born black individuals (USBs) and varies by region of birth, according to a new study.
For instance, the data showed that ABs who immigrated to the US had a higher incidence of leukemia and non-Hodgkin lymphoma (NHL) than USBs.
And there was a higher incidence of NHL among ABs born in Eastern Africa than among those born in Western Africa.
“Typically, cancer occurrence among blacks in the United States is presented as one homogeneous group, with no breakdown by country or region of birth,” said Ahemdin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia.
“Our study shows that approach masks important potential differences that may be key to guiding cancer prevention programs for African-born black immigrants.”
Dr Jemal and his colleagues described this study in the journal Cancer.
The team reviewed cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER 17) program covering the period from 2000 through 2012.
They calculated age-standardized proportional incidence ratios (PIRs), comparing the frequency of the top 15 cancers in ABs with that of USBs, by sex and region of birth.
ABs had a significantly higher proportion of hematologic malignancies (leukemia and NHL), infection-related cancers (liver, stomach, and Kaposi sarcoma), prostate cancer, and thyroid cancers (in females only), when compared to USBs.
In females, the incidence of NHL was 3.4% in ABs and 2.5% in USBs, with a PIR of 1.19. The incidence of leukemia was 3.0% in ABs and 1.9% in USBs, with a PIR of 1.62.
In males, the incidence of NHL was 5.9% in ABs and 3.0% in USBs, with a PIR of 1.34. The incidence of leukemia was 3.0% in ABs and 2.2% in USBs, with a PIR of 1.40.
The investigators also calculated the PIRs of the 5 most frequent cancers in ABs compared to USBs by region of origin (Western Africa vs Eastern Africa).
For both sexes, the incidence of NHL was 4.0% in ABs born in Western Africa (PIR=1.17) and 5.5% in ABs born in Eastern Africa (PIR=1.44).
Leukemia was not included in this analysis because it was not among the top 5 cancers.
Cancer risk, burden expected to shift in HIV population
WASHINGTON, DC—New research suggests HIV-positive adults in the US will see a shift in cancer risk and burden in the coming years.
The study indicates that, through 2030, people living with HIV will see a decrease in AIDS-defining cancers, such as non-Hodgkin lymphoma (NHL) and Kaposi sarcoma.
But this group will also see an increase in cancers not linked to AIDS, such as prostate and liver cancers.
Researchers made these projections in a presentation at the AACR Annual Meeting 2017 (abstract 5302).
“Declines in cancer incidence rates, particularly for AIDS-defining cancers, are likely driven by widespread treatment with modern antiretroviral therapies, which reduce immune suppression and decrease risk of some cancers,” said Jessica Y. Islam, a doctoral student at the University of North Carolina Gillings School of Global Public Health in Chapel Hill.
She and her collaborators estimated future cancer risk and burden for HIV-positive people using age-specific cancer incidence data from the National Cancer Institute HIV/AIDS Cancer Match (HACM) Study, and projected HIV prevalence data from the Centers for Disease Control and Prevention.
Cancer incidence
From 2000 to 2012, there were 23,907 cancers reported in 463,300 HIV-infected adults in the HACM Study. Based on trends in this study, the researchers made projections for cancer incidence through 2030.
They projected that HIV-positive adults of all ages will see a significant decrease over time in the incidence of NHL, Kaposi sarcoma, cervical cancer, anal cancer among men who have sex with men (MSM), lung cancer, and Hodgkin lymphoma.
Patients age 65 and older will see a significant decrease in colon cancer incidence over time. However, there will be no significant change for patients younger than 65.
HIV-positive adults of all ages will see no significant change over time in the incidence of liver cancer, oral cavity cancer, anal cancer among non-MSMs, and breast cancer.
The incidence of prostate cancer will increase significantly among patients ages 35 to 44 and among patients ages 45 to 64.
Cancer burden
The researchers said the number of adults living with HIV in the US is projected to increase from 1.06 million in 2006 to 1.17 million in 2018, but it is expected to decline to 1.09 million in 2030.
The team noted that, in 2006, there were an estimated 8241 cancers in patients with HIV—3522 AIDS-defining cancers and 4719 malignancies not associated with AIDS.
In 2030, the total number of cancers in the HIV-positive population is projected to be 6692, with decreases in AIDS-defining cancers (n=716) and increases in other cancers (n=5976) from the 2006 data.
In 2010, the most common cancers among HIV-positive patients were estimated to be NHL (n=1488), Kaposi sarcoma (n=1133), and lung cancer (n=815).
But in 2030, the most common cancers are projected to be prostate (n=1587), lung (n=1027), and liver cancers (n=483).
“It is critical to understand both incidence rates and burden over time, as rates capture changes in cancer risk, and burden quantifies the actual number of cancer cases expected to occur,” said study investigator Meredith S. Shiels, PhD, of the National Cancer Institute in Bethesda, Maryland.
“For example, lung cancer rates are expected to decrease in the future, but the burden is expected to increase due to the growing number of older people living with HIV.”
WASHINGTON, DC—New research suggests HIV-positive adults in the US will see a shift in cancer risk and burden in the coming years.
The study indicates that, through 2030, people living with HIV will see a decrease in AIDS-defining cancers, such as non-Hodgkin lymphoma (NHL) and Kaposi sarcoma.
But this group will also see an increase in cancers not linked to AIDS, such as prostate and liver cancers.
Researchers made these projections in a presentation at the AACR Annual Meeting 2017 (abstract 5302).
“Declines in cancer incidence rates, particularly for AIDS-defining cancers, are likely driven by widespread treatment with modern antiretroviral therapies, which reduce immune suppression and decrease risk of some cancers,” said Jessica Y. Islam, a doctoral student at the University of North Carolina Gillings School of Global Public Health in Chapel Hill.
She and her collaborators estimated future cancer risk and burden for HIV-positive people using age-specific cancer incidence data from the National Cancer Institute HIV/AIDS Cancer Match (HACM) Study, and projected HIV prevalence data from the Centers for Disease Control and Prevention.
Cancer incidence
From 2000 to 2012, there were 23,907 cancers reported in 463,300 HIV-infected adults in the HACM Study. Based on trends in this study, the researchers made projections for cancer incidence through 2030.
They projected that HIV-positive adults of all ages will see a significant decrease over time in the incidence of NHL, Kaposi sarcoma, cervical cancer, anal cancer among men who have sex with men (MSM), lung cancer, and Hodgkin lymphoma.
Patients age 65 and older will see a significant decrease in colon cancer incidence over time. However, there will be no significant change for patients younger than 65.
HIV-positive adults of all ages will see no significant change over time in the incidence of liver cancer, oral cavity cancer, anal cancer among non-MSMs, and breast cancer.
The incidence of prostate cancer will increase significantly among patients ages 35 to 44 and among patients ages 45 to 64.
Cancer burden
The researchers said the number of adults living with HIV in the US is projected to increase from 1.06 million in 2006 to 1.17 million in 2018, but it is expected to decline to 1.09 million in 2030.
The team noted that, in 2006, there were an estimated 8241 cancers in patients with HIV—3522 AIDS-defining cancers and 4719 malignancies not associated with AIDS.
In 2030, the total number of cancers in the HIV-positive population is projected to be 6692, with decreases in AIDS-defining cancers (n=716) and increases in other cancers (n=5976) from the 2006 data.
In 2010, the most common cancers among HIV-positive patients were estimated to be NHL (n=1488), Kaposi sarcoma (n=1133), and lung cancer (n=815).
But in 2030, the most common cancers are projected to be prostate (n=1587), lung (n=1027), and liver cancers (n=483).
“It is critical to understand both incidence rates and burden over time, as rates capture changes in cancer risk, and burden quantifies the actual number of cancer cases expected to occur,” said study investigator Meredith S. Shiels, PhD, of the National Cancer Institute in Bethesda, Maryland.
“For example, lung cancer rates are expected to decrease in the future, but the burden is expected to increase due to the growing number of older people living with HIV.”
WASHINGTON, DC—New research suggests HIV-positive adults in the US will see a shift in cancer risk and burden in the coming years.
The study indicates that, through 2030, people living with HIV will see a decrease in AIDS-defining cancers, such as non-Hodgkin lymphoma (NHL) and Kaposi sarcoma.
But this group will also see an increase in cancers not linked to AIDS, such as prostate and liver cancers.
Researchers made these projections in a presentation at the AACR Annual Meeting 2017 (abstract 5302).
“Declines in cancer incidence rates, particularly for AIDS-defining cancers, are likely driven by widespread treatment with modern antiretroviral therapies, which reduce immune suppression and decrease risk of some cancers,” said Jessica Y. Islam, a doctoral student at the University of North Carolina Gillings School of Global Public Health in Chapel Hill.
She and her collaborators estimated future cancer risk and burden for HIV-positive people using age-specific cancer incidence data from the National Cancer Institute HIV/AIDS Cancer Match (HACM) Study, and projected HIV prevalence data from the Centers for Disease Control and Prevention.
Cancer incidence
From 2000 to 2012, there were 23,907 cancers reported in 463,300 HIV-infected adults in the HACM Study. Based on trends in this study, the researchers made projections for cancer incidence through 2030.
They projected that HIV-positive adults of all ages will see a significant decrease over time in the incidence of NHL, Kaposi sarcoma, cervical cancer, anal cancer among men who have sex with men (MSM), lung cancer, and Hodgkin lymphoma.
Patients age 65 and older will see a significant decrease in colon cancer incidence over time. However, there will be no significant change for patients younger than 65.
HIV-positive adults of all ages will see no significant change over time in the incidence of liver cancer, oral cavity cancer, anal cancer among non-MSMs, and breast cancer.
The incidence of prostate cancer will increase significantly among patients ages 35 to 44 and among patients ages 45 to 64.
Cancer burden
The researchers said the number of adults living with HIV in the US is projected to increase from 1.06 million in 2006 to 1.17 million in 2018, but it is expected to decline to 1.09 million in 2030.
The team noted that, in 2006, there were an estimated 8241 cancers in patients with HIV—3522 AIDS-defining cancers and 4719 malignancies not associated with AIDS.
In 2030, the total number of cancers in the HIV-positive population is projected to be 6692, with decreases in AIDS-defining cancers (n=716) and increases in other cancers (n=5976) from the 2006 data.
In 2010, the most common cancers among HIV-positive patients were estimated to be NHL (n=1488), Kaposi sarcoma (n=1133), and lung cancer (n=815).
But in 2030, the most common cancers are projected to be prostate (n=1587), lung (n=1027), and liver cancers (n=483).
“It is critical to understand both incidence rates and burden over time, as rates capture changes in cancer risk, and burden quantifies the actual number of cancer cases expected to occur,” said study investigator Meredith S. Shiels, PhD, of the National Cancer Institute in Bethesda, Maryland.
“For example, lung cancer rates are expected to decrease in the future, but the burden is expected to increase due to the growing number of older people living with HIV.”
Drug may be new option for difficult-to-treat DLBCL, doc says
WASHINGTON, DC—Selinexor has demonstrated the potential to become a new oral treatment option for patients with difficult-to-treat diffuse large B-cell lymphoma (DLBCL), according to a presenter at the AACR Annual Meeting 2017.
Interim results from the phase 2b SADAL study showed that selinexor produced a 28.6% overall response rate (ORR), with an 11.1% complete response (CR) rate, in a heavily pretreated, older DLBCL population.
Responses were observed in GCB and non-GCB subtypes, and the median duration of response exceeded 7 months.
The most common adverse events (AEs) were fatigue, thrombocytopenia, nausea, anorexia, and vomiting.
Marie Maerevoet, MD, of the Institute Jules Bordet in Brussels, Belgium, presented data from the SADAL study as abstract CT132/13.*
The trial is sponsored by Karyopharm Therapeutics, the company developing selinexor.
Patients and treatment
The study enrolled 72 patients with relapsed or refractory DLBCL. At least 14 weeks had elapsed since their most recent systemic anti-DLBCL therapy.
The patients received selinexor—an oral selective inhibitor of nuclear export (SINE™) compound—at 60 mg or 100 mg twice weekly (days 1 and 3 each week) of each 28-day cycle.
60 mg arm
There were 37 patients in the 60 mg arm. Their median age was 71 (range, 38-87), and most (n=24) were male. Forty-nine percent of these patients (n=18) had GCB DLBCL.
Fourteen percent of patients had high-risk disease (according to the revised international prognostic index). Forty-three percent had high-intermediate-risk, 30% had low-intermediate-risk, and 14% had low-risk disease.
The patients had received a median of 3 prior treatment regimens (range, 2-5). Twenty-seven percent had received a prior transplant.
100 mg arm
There were 35 patients in the 100 mg arm. Their median age was 68 (range, 32-82), and most (n=23) were male. Fifty-one percent of patients (n=18) had GCB DLBCL.
Eleven percent of patients had high-risk, 40% had high-intermediate-risk, 37% had low-intermediate-risk, and 6% had low-risk disease. For 6% of patients, their risk group was unknown.
The patients had received a median of 3 prior treatment regimens (range, 2-5). Forty-six percent had received a prior transplant.
Safety
All 72 patients were evaluable for safety. The most common AEs across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%), and anemia (32%).
These events were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care.
The 60 mg dose was better tolerated than the 100 mg dose, with fewer dose interruptions and modifications required in the 60 mg arm.
Grade 3/4 AEs that were more common in the 100 mg arm than the 60 mg arm were fatigue (26% vs 11%), thrombocytopenia (46% vs 32%), and anorexia (11% vs 3%).
Efficacy
Sixty-three patients were analyzed for response. The ORR was 28.6% (18/63), with a CR rate of 11.1% (n=7) and a partial response (PR) rate of 17.5% (n=11).
The rate of stable disease (SD) was 14.3% (n=9), and the rate of progressive disease (PD) was 46% (n=29). Seven patients (11.1%) were not evaluable (NE).
The best responses as of March 1, 2017, according to subtype and selinexor dose, were as follows:
| Category | N | ORR | CR | PR | SD | PD | NE |
| 60 mg | 32 | 9 (28.1%) | 4 (12.5%) | 5 (15.6%) | 3 (9.4%) | 17 (53.1%) | 3 (9.4%) |
| 100 mg | 31 | 9 (29.0%) | 3 (9.7%) | 6 (19.4%) | 6 (19.4%) | 12 (38.7%) | 4 (12.9%) |
| GCB subtype | 32 | 8 (25.0%) | 3 (9.4%) | 5 (15.6%) | 6 (18.8%) | 13 (40.6%) | 5 (15.6%) |
| Non-GCB subtype | 31 | 10 (32.3%) | 4 (12.9%) | 6 (19.4%) | 3 (9.7%) | 16 (51.6%) | 2 (6.5%) |
The median duration of response was greater than 7 months. The median time to response was 2 months.
Among responders, the median time on treatment was 9 months, with a median follow-up of 13 months. As of the data cutoff date, 9 responders remained on treatment, including 6 patients with a CR.
The median overall survival was 8 months for all patients. As of the cutoff date, the median survival for the responders had not been reached.
“With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult-to-treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents,” Dr Maerevoet said.
Trial update
As a result of the interim data from SADAL, and in consultation with the US Food and Drug Administration (FDA), Karyopharm is amending the study protocol.
SADAL will become a single-arm study focusing solely on single-agent selinexor dosed at 60 mg twice weekly.
The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory to or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period.
Karyopharm plans to enroll up to an additional 90 patients to the new 60 mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.
The FDA recently lifted a partial clinical hold placed on the SADAL trial and other trials of selinexor.
The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
*Data in the abstract differ from the presentation.
WASHINGTON, DC—Selinexor has demonstrated the potential to become a new oral treatment option for patients with difficult-to-treat diffuse large B-cell lymphoma (DLBCL), according to a presenter at the AACR Annual Meeting 2017.
Interim results from the phase 2b SADAL study showed that selinexor produced a 28.6% overall response rate (ORR), with an 11.1% complete response (CR) rate, in a heavily pretreated, older DLBCL population.
Responses were observed in GCB and non-GCB subtypes, and the median duration of response exceeded 7 months.
The most common adverse events (AEs) were fatigue, thrombocytopenia, nausea, anorexia, and vomiting.
Marie Maerevoet, MD, of the Institute Jules Bordet in Brussels, Belgium, presented data from the SADAL study as abstract CT132/13.*
The trial is sponsored by Karyopharm Therapeutics, the company developing selinexor.
Patients and treatment
The study enrolled 72 patients with relapsed or refractory DLBCL. At least 14 weeks had elapsed since their most recent systemic anti-DLBCL therapy.
The patients received selinexor—an oral selective inhibitor of nuclear export (SINE™) compound—at 60 mg or 100 mg twice weekly (days 1 and 3 each week) of each 28-day cycle.
60 mg arm
There were 37 patients in the 60 mg arm. Their median age was 71 (range, 38-87), and most (n=24) were male. Forty-nine percent of these patients (n=18) had GCB DLBCL.
Fourteen percent of patients had high-risk disease (according to the revised international prognostic index). Forty-three percent had high-intermediate-risk, 30% had low-intermediate-risk, and 14% had low-risk disease.
The patients had received a median of 3 prior treatment regimens (range, 2-5). Twenty-seven percent had received a prior transplant.
100 mg arm
There were 35 patients in the 100 mg arm. Their median age was 68 (range, 32-82), and most (n=23) were male. Fifty-one percent of patients (n=18) had GCB DLBCL.
Eleven percent of patients had high-risk, 40% had high-intermediate-risk, 37% had low-intermediate-risk, and 6% had low-risk disease. For 6% of patients, their risk group was unknown.
The patients had received a median of 3 prior treatment regimens (range, 2-5). Forty-six percent had received a prior transplant.
Safety
All 72 patients were evaluable for safety. The most common AEs across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%), and anemia (32%).
These events were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care.
The 60 mg dose was better tolerated than the 100 mg dose, with fewer dose interruptions and modifications required in the 60 mg arm.
Grade 3/4 AEs that were more common in the 100 mg arm than the 60 mg arm were fatigue (26% vs 11%), thrombocytopenia (46% vs 32%), and anorexia (11% vs 3%).
Efficacy
Sixty-three patients were analyzed for response. The ORR was 28.6% (18/63), with a CR rate of 11.1% (n=7) and a partial response (PR) rate of 17.5% (n=11).
The rate of stable disease (SD) was 14.3% (n=9), and the rate of progressive disease (PD) was 46% (n=29). Seven patients (11.1%) were not evaluable (NE).
The best responses as of March 1, 2017, according to subtype and selinexor dose, were as follows:
| Category | N | ORR | CR | PR | SD | PD | NE |
| 60 mg | 32 | 9 (28.1%) | 4 (12.5%) | 5 (15.6%) | 3 (9.4%) | 17 (53.1%) | 3 (9.4%) |
| 100 mg | 31 | 9 (29.0%) | 3 (9.7%) | 6 (19.4%) | 6 (19.4%) | 12 (38.7%) | 4 (12.9%) |
| GCB subtype | 32 | 8 (25.0%) | 3 (9.4%) | 5 (15.6%) | 6 (18.8%) | 13 (40.6%) | 5 (15.6%) |
| Non-GCB subtype | 31 | 10 (32.3%) | 4 (12.9%) | 6 (19.4%) | 3 (9.7%) | 16 (51.6%) | 2 (6.5%) |
The median duration of response was greater than 7 months. The median time to response was 2 months.
Among responders, the median time on treatment was 9 months, with a median follow-up of 13 months. As of the data cutoff date, 9 responders remained on treatment, including 6 patients with a CR.
The median overall survival was 8 months for all patients. As of the cutoff date, the median survival for the responders had not been reached.
“With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult-to-treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents,” Dr Maerevoet said.
Trial update
As a result of the interim data from SADAL, and in consultation with the US Food and Drug Administration (FDA), Karyopharm is amending the study protocol.
SADAL will become a single-arm study focusing solely on single-agent selinexor dosed at 60 mg twice weekly.
The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory to or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period.
Karyopharm plans to enroll up to an additional 90 patients to the new 60 mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.
The FDA recently lifted a partial clinical hold placed on the SADAL trial and other trials of selinexor.
The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
*Data in the abstract differ from the presentation.
WASHINGTON, DC—Selinexor has demonstrated the potential to become a new oral treatment option for patients with difficult-to-treat diffuse large B-cell lymphoma (DLBCL), according to a presenter at the AACR Annual Meeting 2017.
Interim results from the phase 2b SADAL study showed that selinexor produced a 28.6% overall response rate (ORR), with an 11.1% complete response (CR) rate, in a heavily pretreated, older DLBCL population.
Responses were observed in GCB and non-GCB subtypes, and the median duration of response exceeded 7 months.
The most common adverse events (AEs) were fatigue, thrombocytopenia, nausea, anorexia, and vomiting.
Marie Maerevoet, MD, of the Institute Jules Bordet in Brussels, Belgium, presented data from the SADAL study as abstract CT132/13.*
The trial is sponsored by Karyopharm Therapeutics, the company developing selinexor.
Patients and treatment
The study enrolled 72 patients with relapsed or refractory DLBCL. At least 14 weeks had elapsed since their most recent systemic anti-DLBCL therapy.
The patients received selinexor—an oral selective inhibitor of nuclear export (SINE™) compound—at 60 mg or 100 mg twice weekly (days 1 and 3 each week) of each 28-day cycle.
60 mg arm
There were 37 patients in the 60 mg arm. Their median age was 71 (range, 38-87), and most (n=24) were male. Forty-nine percent of these patients (n=18) had GCB DLBCL.
Fourteen percent of patients had high-risk disease (according to the revised international prognostic index). Forty-three percent had high-intermediate-risk, 30% had low-intermediate-risk, and 14% had low-risk disease.
The patients had received a median of 3 prior treatment regimens (range, 2-5). Twenty-seven percent had received a prior transplant.
100 mg arm
There were 35 patients in the 100 mg arm. Their median age was 68 (range, 32-82), and most (n=23) were male. Fifty-one percent of patients (n=18) had GCB DLBCL.
Eleven percent of patients had high-risk, 40% had high-intermediate-risk, 37% had low-intermediate-risk, and 6% had low-risk disease. For 6% of patients, their risk group was unknown.
The patients had received a median of 3 prior treatment regimens (range, 2-5). Forty-six percent had received a prior transplant.
Safety
All 72 patients were evaluable for safety. The most common AEs across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%), and anemia (32%).
These events were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care.
The 60 mg dose was better tolerated than the 100 mg dose, with fewer dose interruptions and modifications required in the 60 mg arm.
Grade 3/4 AEs that were more common in the 100 mg arm than the 60 mg arm were fatigue (26% vs 11%), thrombocytopenia (46% vs 32%), and anorexia (11% vs 3%).
Efficacy
Sixty-three patients were analyzed for response. The ORR was 28.6% (18/63), with a CR rate of 11.1% (n=7) and a partial response (PR) rate of 17.5% (n=11).
The rate of stable disease (SD) was 14.3% (n=9), and the rate of progressive disease (PD) was 46% (n=29). Seven patients (11.1%) were not evaluable (NE).
The best responses as of March 1, 2017, according to subtype and selinexor dose, were as follows:
| Category | N | ORR | CR | PR | SD | PD | NE |
| 60 mg | 32 | 9 (28.1%) | 4 (12.5%) | 5 (15.6%) | 3 (9.4%) | 17 (53.1%) | 3 (9.4%) |
| 100 mg | 31 | 9 (29.0%) | 3 (9.7%) | 6 (19.4%) | 6 (19.4%) | 12 (38.7%) | 4 (12.9%) |
| GCB subtype | 32 | 8 (25.0%) | 3 (9.4%) | 5 (15.6%) | 6 (18.8%) | 13 (40.6%) | 5 (15.6%) |
| Non-GCB subtype | 31 | 10 (32.3%) | 4 (12.9%) | 6 (19.4%) | 3 (9.7%) | 16 (51.6%) | 2 (6.5%) |
The median duration of response was greater than 7 months. The median time to response was 2 months.
Among responders, the median time on treatment was 9 months, with a median follow-up of 13 months. As of the data cutoff date, 9 responders remained on treatment, including 6 patients with a CR.
The median overall survival was 8 months for all patients. As of the cutoff date, the median survival for the responders had not been reached.
“With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult-to-treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents,” Dr Maerevoet said.
Trial update
As a result of the interim data from SADAL, and in consultation with the US Food and Drug Administration (FDA), Karyopharm is amending the study protocol.
SADAL will become a single-arm study focusing solely on single-agent selinexor dosed at 60 mg twice weekly.
The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory to or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period.
Karyopharm plans to enroll up to an additional 90 patients to the new 60 mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.
The FDA recently lifted a partial clinical hold placed on the SADAL trial and other trials of selinexor.
The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
*Data in the abstract differ from the presentation.
Inhibitor produces durable responses in rel/ref iNHL
WASHINGTON, DC—An investigational drug can produce durable responses and has a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), according to researchers.
The drug is copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor.
In the phase 2 CHRONOS-1 trial, copanlisib produced an objective response rate (ORR) of 59.2%, with a complete response (CR) rate of 12%, in patients with relapsed/refractory iNHL.
The median duration of response exceeded 98 weeks.
There were 3 deaths considered related to copanlisib, and the most common treatment-related adverse events (AEs) were transient hyperglycemia and hypertension.
These results were presented at the AACR Annual Meeting 2017 (abstract CT149). The study is supported by Bayer, the company developing copanlisib.
CHRONOS-1 included 141 patients with iNHL. Most (n=104) had follicular lymphoma (FL), 23 had marginal zone lymphoma (MZL), 8 had small lymphocytic lymphoma, and 6 had lymphoplasmacytoid/Waldenstrӧm’s macroglobulinemia.
All patients had relapsed after or were refractory to at least 2 prior lines of therapy, which included both rituximab and an alkylating agent.
For this study, the patients received 60 mg of intravenous copanlisib intermittently on days 1, 8, and 15 of a 28-day cycle.
At the time of analysis, the median duration of treatment was 22 weeks (range, 1-105), and 46 patients were still receiving copanlisib.
Efficacy
For the entire cohort, the ORR was 59.2%. Twelve percent of patients achieved a CR, 47.2% had a partial response (PR), 29.6% had stable disease, and 2.1% had progressive disease.
Among patients with FL, the ORR was 58.7%, the CR rate was 14.4%, and the PR rate was 44.2%.
Among patients with MZL, the ORR was 69.6%, with 8.7% of patients achieving a CR and 60.9% achieving a PR.
For the entire cohort, the estimated median duration of response was 687 days (range, 0-687). For patients with FL, it was 370 days (range, 0-687).
The estimated median progression-free survival was 340 days (range, 0-736), and the median overall survival had not been reached at the time of analysis.
Safety
The most common treatment-related AEs were transient hyperglycemia (all grades, 49%/grade 3+, 40%) and hypertension (all grades, 29%/grade 3+, 23%).
The researchers said other AEs of interest were neutropenia (all grades, 25%/grade 3+, 19%), diarrhea (all grades, 18%/grade 3+, 4%), lung infection (all grades, 14%/grade 3+, 11%), pneumonitis (all grades, 7%/grade 3+, 1.4%), and colitis (0.7%, all grade 3+).
Laboratory AEs of interest were alanine aminotransferase increase (all grades, 23%/grade 1, 19%) and aspartate aminotransferase increase (all grades, 28%/grade 1, 25%).
There were 2 non-fatal opportunistic infections.
There were 6 deaths, and 3 of them were considered related to copanlisib. These 3 deaths were due to lung infection, respiratory failure, and a thromboembolic event.
“[I]nhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas . . .,” said study investigator Martin Dreyling, MD, of Klinikum der Universität München-Grosshadern in Munich, Germany.
“However, concerns exist about the safety of available oral PI3K inhibitors . . . . The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population.”
WASHINGTON, DC—An investigational drug can produce durable responses and has a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), according to researchers.
The drug is copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor.
In the phase 2 CHRONOS-1 trial, copanlisib produced an objective response rate (ORR) of 59.2%, with a complete response (CR) rate of 12%, in patients with relapsed/refractory iNHL.
The median duration of response exceeded 98 weeks.
There were 3 deaths considered related to copanlisib, and the most common treatment-related adverse events (AEs) were transient hyperglycemia and hypertension.
These results were presented at the AACR Annual Meeting 2017 (abstract CT149). The study is supported by Bayer, the company developing copanlisib.
CHRONOS-1 included 141 patients with iNHL. Most (n=104) had follicular lymphoma (FL), 23 had marginal zone lymphoma (MZL), 8 had small lymphocytic lymphoma, and 6 had lymphoplasmacytoid/Waldenstrӧm’s macroglobulinemia.
All patients had relapsed after or were refractory to at least 2 prior lines of therapy, which included both rituximab and an alkylating agent.
For this study, the patients received 60 mg of intravenous copanlisib intermittently on days 1, 8, and 15 of a 28-day cycle.
At the time of analysis, the median duration of treatment was 22 weeks (range, 1-105), and 46 patients were still receiving copanlisib.
Efficacy
For the entire cohort, the ORR was 59.2%. Twelve percent of patients achieved a CR, 47.2% had a partial response (PR), 29.6% had stable disease, and 2.1% had progressive disease.
Among patients with FL, the ORR was 58.7%, the CR rate was 14.4%, and the PR rate was 44.2%.
Among patients with MZL, the ORR was 69.6%, with 8.7% of patients achieving a CR and 60.9% achieving a PR.
For the entire cohort, the estimated median duration of response was 687 days (range, 0-687). For patients with FL, it was 370 days (range, 0-687).
The estimated median progression-free survival was 340 days (range, 0-736), and the median overall survival had not been reached at the time of analysis.
Safety
The most common treatment-related AEs were transient hyperglycemia (all grades, 49%/grade 3+, 40%) and hypertension (all grades, 29%/grade 3+, 23%).
The researchers said other AEs of interest were neutropenia (all grades, 25%/grade 3+, 19%), diarrhea (all grades, 18%/grade 3+, 4%), lung infection (all grades, 14%/grade 3+, 11%), pneumonitis (all grades, 7%/grade 3+, 1.4%), and colitis (0.7%, all grade 3+).
Laboratory AEs of interest were alanine aminotransferase increase (all grades, 23%/grade 1, 19%) and aspartate aminotransferase increase (all grades, 28%/grade 1, 25%).
There were 2 non-fatal opportunistic infections.
There were 6 deaths, and 3 of them were considered related to copanlisib. These 3 deaths were due to lung infection, respiratory failure, and a thromboembolic event.
“[I]nhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas . . .,” said study investigator Martin Dreyling, MD, of Klinikum der Universität München-Grosshadern in Munich, Germany.
“However, concerns exist about the safety of available oral PI3K inhibitors . . . . The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population.”
WASHINGTON, DC—An investigational drug can produce durable responses and has a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL), according to researchers.
The drug is copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor.
In the phase 2 CHRONOS-1 trial, copanlisib produced an objective response rate (ORR) of 59.2%, with a complete response (CR) rate of 12%, in patients with relapsed/refractory iNHL.
The median duration of response exceeded 98 weeks.
There were 3 deaths considered related to copanlisib, and the most common treatment-related adverse events (AEs) were transient hyperglycemia and hypertension.
These results were presented at the AACR Annual Meeting 2017 (abstract CT149). The study is supported by Bayer, the company developing copanlisib.
CHRONOS-1 included 141 patients with iNHL. Most (n=104) had follicular lymphoma (FL), 23 had marginal zone lymphoma (MZL), 8 had small lymphocytic lymphoma, and 6 had lymphoplasmacytoid/Waldenstrӧm’s macroglobulinemia.
All patients had relapsed after or were refractory to at least 2 prior lines of therapy, which included both rituximab and an alkylating agent.
For this study, the patients received 60 mg of intravenous copanlisib intermittently on days 1, 8, and 15 of a 28-day cycle.
At the time of analysis, the median duration of treatment was 22 weeks (range, 1-105), and 46 patients were still receiving copanlisib.
Efficacy
For the entire cohort, the ORR was 59.2%. Twelve percent of patients achieved a CR, 47.2% had a partial response (PR), 29.6% had stable disease, and 2.1% had progressive disease.
Among patients with FL, the ORR was 58.7%, the CR rate was 14.4%, and the PR rate was 44.2%.
Among patients with MZL, the ORR was 69.6%, with 8.7% of patients achieving a CR and 60.9% achieving a PR.
For the entire cohort, the estimated median duration of response was 687 days (range, 0-687). For patients with FL, it was 370 days (range, 0-687).
The estimated median progression-free survival was 340 days (range, 0-736), and the median overall survival had not been reached at the time of analysis.
Safety
The most common treatment-related AEs were transient hyperglycemia (all grades, 49%/grade 3+, 40%) and hypertension (all grades, 29%/grade 3+, 23%).
The researchers said other AEs of interest were neutropenia (all grades, 25%/grade 3+, 19%), diarrhea (all grades, 18%/grade 3+, 4%), lung infection (all grades, 14%/grade 3+, 11%), pneumonitis (all grades, 7%/grade 3+, 1.4%), and colitis (0.7%, all grade 3+).
Laboratory AEs of interest were alanine aminotransferase increase (all grades, 23%/grade 1, 19%) and aspartate aminotransferase increase (all grades, 28%/grade 1, 25%).
There were 2 non-fatal opportunistic infections.
There were 6 deaths, and 3 of them were considered related to copanlisib. These 3 deaths were due to lung infection, respiratory failure, and a thromboembolic event.
“[I]nhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas . . .,” said study investigator Martin Dreyling, MD, of Klinikum der Universität München-Grosshadern in Munich, Germany.
“However, concerns exist about the safety of available oral PI3K inhibitors . . . . The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population.”
Half of patients retain response to CAR T-cell therapy
WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.
The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).
At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).
Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.
There were 2 deaths related to axicabtagene ciloleucel.
Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).
ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.
Patients and treatment
The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.
Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.
Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.
Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.
For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days.
Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 106 CAR T cells/kg.
Efficacy
The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.
| DLBCL (n=77) | TFL/PMBCL (n=24) | Combined (n=101) | ||||
| ORR (%) | CR (%) | ORR (%) | CR (%) | ORR (%) | CR (%) | |
| ORR | 82 | 49 | 83 | 71 | 82 | 54 |
| Month 6 | 36 | 31 | 54 | 50 | 41 | 36 |
| Ongoing | 36 | 31 | 67 | 63 | 44 | 39 |
The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.
Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.
At a median follow-up of 8.7 months, the median overall survival has not been reached.
Safety
The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).
The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.
“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.
There were 3 deaths throughout the course of the trial that were not a result of disease progression.
Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.
The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.
WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.
The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).
At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).
Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.
There were 2 deaths related to axicabtagene ciloleucel.
Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).
ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.
Patients and treatment
The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.
Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.
Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.
Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.
For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days.
Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 106 CAR T cells/kg.
Efficacy
The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.
| DLBCL (n=77) | TFL/PMBCL (n=24) | Combined (n=101) | ||||
| ORR (%) | CR (%) | ORR (%) | CR (%) | ORR (%) | CR (%) | |
| ORR | 82 | 49 | 83 | 71 | 82 | 54 |
| Month 6 | 36 | 31 | 54 | 50 | 41 | 36 |
| Ongoing | 36 | 31 | 67 | 63 | 44 | 39 |
The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.
Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.
At a median follow-up of 8.7 months, the median overall survival has not been reached.
Safety
The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).
The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.
“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.
There were 3 deaths throughout the course of the trial that were not a result of disease progression.
Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.
The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.
WASHINGTON, DC—Roughly half of patients who responded to chimeric antigen receptor (CAR) T-cell therapy in the ZUMA-1 trial have retained that response at a median follow-up exceeding 8 months.
The CAR T-cell therapy, axicabtagene ciloleucel (formerly KTE-C19), initially produced an objective response rate (ORR) of 82% in this trial of patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).
At a median follow-up of 8.7 months, 44% of all patients (53% of responders) are still in response, and 39% are in complete response (CR).
Thirteen percent of patients had grade 3 or higher cytokine release syndrome (CRS), and 28% had neurologic events.
There were 2 deaths related to axicabtagene ciloleucel.
Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida, presented these updated results from ZUMA-1 at the AACR Annual Meeting 2017 (abstract CT019).
ZUMA-1 is sponsored by Kite Pharma but is also funded, in part, by the Leukemia and Lymphoma Society Therapy Acceleration Program.
Patients and treatment
The trial enrolled 111 patients, 101 of whom were successfully treated with axicabtagene ciloleucel. Seven patients could not be treated due to serious adverse events, 1 due to unavailable product, and 2 due to non-measurable disease.
Seventy-seven of the patients had diffuse large B-cell lymphoma (DLBCL), and 24 had transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL). Eighty-five percent of patients had stage III/IV disease.
Seventy-nine percent were refractory to chemotherapy and did not have a prior autologous stem cell transplant (auto-SCT). Twenty-one percent did undergo auto-SCT and relapsed within 12 months of the procedure.
Sixty-nine percent of patients had received 3 or more lines of prior therapy, and 54% were refractory to 2 consecutive lines of prior therapy.
For this study, the patients received a conditioning regimen of cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days.
Two days after the conditioning regimen was completed, patients received axicabtagene ciloleucel at a target dose of 2 × 106 CAR T cells/kg.
Efficacy
The following table shows overall response data, response data at 6 months, and ongoing responses at the primary analysis data cut-off.
| DLBCL (n=77) | TFL/PMBCL (n=24) | Combined (n=101) | ||||
| ORR (%) | CR (%) | ORR (%) | CR (%) | ORR (%) | CR (%) | |
| ORR | 82 | 49 | 83 | 71 | 82 | 54 |
| Month 6 | 36 | 31 | 54 | 50 | 41 | 36 |
| Ongoing | 36 | 31 | 67 | 63 | 44 | 39 |
The researchers said the ORR was generally consistent in key subgroups. The ORR was 83% in patients who were refractory to their second or greater line of therapy and 76% in patients who relapsed within 12 months of auto-SCT.
Overall, the median duration of response was 8.2 months. However, the median duration of response has not been reached for patients with a CR.
At a median follow-up of 8.7 months, the median overall survival has not been reached.
Safety
The most common grade 3 or higher adverse events included anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).
The incidence of grade 3 or higher CRS was 13%, and the incidence of neurologic events was 28%. These represent decreases from the interim analysis of ZUMA-1, when the rate of grade 3+ CRS was 18%, and the rate of neurological events was 34%.
“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” said Jeff Wiezorek, MD, senior vice-president of clinical development at Kite Pharma.
There were 3 deaths throughout the course of the trial that were not a result of disease progression.
Two deaths were deemed related to axicabtagene ciloleucel. One was a case of hemophagocytic lymphohistiocytosis. The other was cardiac arrest in the setting of CRS.
The third death was the result of a pulmonary embolism and was considered unrelated to axicabtagene ciloleucel.
New BTK inhibitor may overcome resistance in CLL
WASHINGTON, DC—Preclinical research suggests a second-generation BTK inhibitor may overcome the acquired resistance observed with its predecessor in patients with chronic lymphocytic leukemia (CLL).
Investigators found the non-covalent BTK inhibitor SNS-062 was unaffected by the BTK C481S mutation, which confers resistance to the first-generation BTK inhibitor ibrutinib.
“[A] subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Amy Johnson, PhD, of The Ohio State University in Columbus.
“A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S.”
“In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”
Dr Johnson and her colleagues presented these findings at the AACR Annual Meeting 2017 (abstract 1207).
SNS-062 is being developed by Sunesis Pharmaceuticals, Inc., and company investigators were involved in this research. But the study was sponsored by The Ohio State University.
For this study, Dr Johnson and her colleagues tested SNS-062 in primary CLL cells and X-linked agammaglobulinemia human cell lines.
The investigators found that SNS-062 inhibited BTK, decreased the expression of B-cell activation markers, and reduced CLL cell viability in a dose-dependent manner. And these effects were comparable to those observed with ibrutinib.
SNS-062 and ibrutinib demonstrated comparable activity against wild-type BTK. However, ibrutinib and another BTK inhibitor, acalabrutinib, were hindered by the BTK C481S mutation, while SNS-062 was not.
The investigators said SNS-062 was 6 times more potent than ibrutinib against C481S BTK and more than 640 times more potent than acalabrutinib.
The team also noted that SNS-062 exhibited high specificity, affecting a limited number of kinases outside the TEC kinase family.
Finally, the investigators found that SNS-062 diminished stromal cell protection in CLL cells, suggesting the drug can hinder protection from the tumor microenvironment.
WASHINGTON, DC—Preclinical research suggests a second-generation BTK inhibitor may overcome the acquired resistance observed with its predecessor in patients with chronic lymphocytic leukemia (CLL).
Investigators found the non-covalent BTK inhibitor SNS-062 was unaffected by the BTK C481S mutation, which confers resistance to the first-generation BTK inhibitor ibrutinib.
“[A] subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Amy Johnson, PhD, of The Ohio State University in Columbus.
“A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S.”
“In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”
Dr Johnson and her colleagues presented these findings at the AACR Annual Meeting 2017 (abstract 1207).
SNS-062 is being developed by Sunesis Pharmaceuticals, Inc., and company investigators were involved in this research. But the study was sponsored by The Ohio State University.
For this study, Dr Johnson and her colleagues tested SNS-062 in primary CLL cells and X-linked agammaglobulinemia human cell lines.
The investigators found that SNS-062 inhibited BTK, decreased the expression of B-cell activation markers, and reduced CLL cell viability in a dose-dependent manner. And these effects were comparable to those observed with ibrutinib.
SNS-062 and ibrutinib demonstrated comparable activity against wild-type BTK. However, ibrutinib and another BTK inhibitor, acalabrutinib, were hindered by the BTK C481S mutation, while SNS-062 was not.
The investigators said SNS-062 was 6 times more potent than ibrutinib against C481S BTK and more than 640 times more potent than acalabrutinib.
The team also noted that SNS-062 exhibited high specificity, affecting a limited number of kinases outside the TEC kinase family.
Finally, the investigators found that SNS-062 diminished stromal cell protection in CLL cells, suggesting the drug can hinder protection from the tumor microenvironment.
WASHINGTON, DC—Preclinical research suggests a second-generation BTK inhibitor may overcome the acquired resistance observed with its predecessor in patients with chronic lymphocytic leukemia (CLL).
Investigators found the non-covalent BTK inhibitor SNS-062 was unaffected by the BTK C481S mutation, which confers resistance to the first-generation BTK inhibitor ibrutinib.
“[A] subset of patients acquire resistance to ibrutinib, the current standard-of-care BTK inhibitor,” said Amy Johnson, PhD, of The Ohio State University in Columbus.
“A key resistance mechanism to covalent BTK inhibitors is a point mutation in the BTK active site, converting cysteine 481 to serine, or C481S.”
“In this study, we demonstrate that SNS-062, which binds non-covalently to BTK, is a potent inhibitor of BTK unaffected by the presence of the C481S mutation. These findings support clinical investigation of SNS-062 to address acquired resistance to covalent BTK inhibitors in patients.”
Dr Johnson and her colleagues presented these findings at the AACR Annual Meeting 2017 (abstract 1207).
SNS-062 is being developed by Sunesis Pharmaceuticals, Inc., and company investigators were involved in this research. But the study was sponsored by The Ohio State University.
For this study, Dr Johnson and her colleagues tested SNS-062 in primary CLL cells and X-linked agammaglobulinemia human cell lines.
The investigators found that SNS-062 inhibited BTK, decreased the expression of B-cell activation markers, and reduced CLL cell viability in a dose-dependent manner. And these effects were comparable to those observed with ibrutinib.
SNS-062 and ibrutinib demonstrated comparable activity against wild-type BTK. However, ibrutinib and another BTK inhibitor, acalabrutinib, were hindered by the BTK C481S mutation, while SNS-062 was not.
The investigators said SNS-062 was 6 times more potent than ibrutinib against C481S BTK and more than 640 times more potent than acalabrutinib.
The team also noted that SNS-062 exhibited high specificity, affecting a limited number of kinases outside the TEC kinase family.
Finally, the investigators found that SNS-062 diminished stromal cell protection in CLL cells, suggesting the drug can hinder protection from the tumor microenvironment.
Report shows increase in blood cancer incidence and survival
A report on cancer in the US suggests the incidence of leukemia and myeloma has been on the rise in recent years, but the incidence of non-Hodgkin lymphoma (NHL) has been on the decline.
Meanwhile, annual death rates for leukemia and NHL have decreased, and annual death rates for myeloma have decreased in men but not in women.
Furthermore, patients with leukemia, NHL, and myeloma have seen a substantial improvement in 5-year survival rates in recent years relative to patients in the late 1970s.
These findings are part of the Annual Report to the Nation on the Status of Cancer, 1975-2014, which has been published in the Journal of the National Cancer Institute.
This report is released each year, but the current edition includes a special section focused on survival.
“While trends in death rates are the most commonly used measure to assess progress against cancer, survival trends are also an important measure to evaluate progress in improvement of cancer outcomes,” said Ahmedin Jemal, DVM, PhD, of the American Cancer Society.
“We last included a special section on cancer survival in 2004, and, as we found then, survival improved over time for almost all cancers at every stage of diagnosis.”
For the current report, researchers calculated the 5-year average annual percent changes (AAPCs) for 2009 to 2013 for cancer incidence and for 2010 to 2014 for cancer mortality.
Cancer incidence (2009-2013)
In women, the AAPC increased 1.5% for leukemia (P<0.05), decreased 0.5% for NHL (P<0.05), and increased 2.2% for myeloma (P<0.05).
In men, the AAPC increased 1.7% for leukemia (P<0.05), decreased 0.2% for NHL, and increased 2.8% for myeloma (P<0.05).
Cancer mortality (2010-2014)
In women, the AAPC decreased 1.2% for leukemia (P<0.05), decreased 2.2% for NHL (P<0.05), and increased 0.5% for myeloma.
In men, the AAPC decreased 1.0% for leukemia (P<0.05), decreased 2.0% for NHL (P<0.05), and decreased 0.9% for myeloma (P<0.05).
5-year survival
The researchers compared 5-year relative survival for cancers diagnosed from 1975 to 1977 and those diagnosed from 2006 to 2012.
The absolute percentage change over time (for both sexes combined) was 26.1% for NHL, 25.7% for myeloma, and 28.5% for leukemia.
Five-year survival for patients diagnosed in 1975-1977 was 46.5% for NHL, 24.6% for myeloma, and 34.2% for leukemia.
Five-year survival for patients diagnosed in 2006-2012 was 72.6% for NHL, 50.2% for myeloma, and 62.7% for leukemia.
A report on cancer in the US suggests the incidence of leukemia and myeloma has been on the rise in recent years, but the incidence of non-Hodgkin lymphoma (NHL) has been on the decline.
Meanwhile, annual death rates for leukemia and NHL have decreased, and annual death rates for myeloma have decreased in men but not in women.
Furthermore, patients with leukemia, NHL, and myeloma have seen a substantial improvement in 5-year survival rates in recent years relative to patients in the late 1970s.
These findings are part of the Annual Report to the Nation on the Status of Cancer, 1975-2014, which has been published in the Journal of the National Cancer Institute.
This report is released each year, but the current edition includes a special section focused on survival.
“While trends in death rates are the most commonly used measure to assess progress against cancer, survival trends are also an important measure to evaluate progress in improvement of cancer outcomes,” said Ahmedin Jemal, DVM, PhD, of the American Cancer Society.
“We last included a special section on cancer survival in 2004, and, as we found then, survival improved over time for almost all cancers at every stage of diagnosis.”
For the current report, researchers calculated the 5-year average annual percent changes (AAPCs) for 2009 to 2013 for cancer incidence and for 2010 to 2014 for cancer mortality.
Cancer incidence (2009-2013)
In women, the AAPC increased 1.5% for leukemia (P<0.05), decreased 0.5% for NHL (P<0.05), and increased 2.2% for myeloma (P<0.05).
In men, the AAPC increased 1.7% for leukemia (P<0.05), decreased 0.2% for NHL, and increased 2.8% for myeloma (P<0.05).
Cancer mortality (2010-2014)
In women, the AAPC decreased 1.2% for leukemia (P<0.05), decreased 2.2% for NHL (P<0.05), and increased 0.5% for myeloma.
In men, the AAPC decreased 1.0% for leukemia (P<0.05), decreased 2.0% for NHL (P<0.05), and decreased 0.9% for myeloma (P<0.05).
5-year survival
The researchers compared 5-year relative survival for cancers diagnosed from 1975 to 1977 and those diagnosed from 2006 to 2012.
The absolute percentage change over time (for both sexes combined) was 26.1% for NHL, 25.7% for myeloma, and 28.5% for leukemia.
Five-year survival for patients diagnosed in 1975-1977 was 46.5% for NHL, 24.6% for myeloma, and 34.2% for leukemia.
Five-year survival for patients diagnosed in 2006-2012 was 72.6% for NHL, 50.2% for myeloma, and 62.7% for leukemia.
A report on cancer in the US suggests the incidence of leukemia and myeloma has been on the rise in recent years, but the incidence of non-Hodgkin lymphoma (NHL) has been on the decline.
Meanwhile, annual death rates for leukemia and NHL have decreased, and annual death rates for myeloma have decreased in men but not in women.
Furthermore, patients with leukemia, NHL, and myeloma have seen a substantial improvement in 5-year survival rates in recent years relative to patients in the late 1970s.
These findings are part of the Annual Report to the Nation on the Status of Cancer, 1975-2014, which has been published in the Journal of the National Cancer Institute.
This report is released each year, but the current edition includes a special section focused on survival.
“While trends in death rates are the most commonly used measure to assess progress against cancer, survival trends are also an important measure to evaluate progress in improvement of cancer outcomes,” said Ahmedin Jemal, DVM, PhD, of the American Cancer Society.
“We last included a special section on cancer survival in 2004, and, as we found then, survival improved over time for almost all cancers at every stage of diagnosis.”
For the current report, researchers calculated the 5-year average annual percent changes (AAPCs) for 2009 to 2013 for cancer incidence and for 2010 to 2014 for cancer mortality.
Cancer incidence (2009-2013)
In women, the AAPC increased 1.5% for leukemia (P<0.05), decreased 0.5% for NHL (P<0.05), and increased 2.2% for myeloma (P<0.05).
In men, the AAPC increased 1.7% for leukemia (P<0.05), decreased 0.2% for NHL, and increased 2.8% for myeloma (P<0.05).
Cancer mortality (2010-2014)
In women, the AAPC decreased 1.2% for leukemia (P<0.05), decreased 2.2% for NHL (P<0.05), and increased 0.5% for myeloma.
In men, the AAPC decreased 1.0% for leukemia (P<0.05), decreased 2.0% for NHL (P<0.05), and decreased 0.9% for myeloma (P<0.05).
5-year survival
The researchers compared 5-year relative survival for cancers diagnosed from 1975 to 1977 and those diagnosed from 2006 to 2012.
The absolute percentage change over time (for both sexes combined) was 26.1% for NHL, 25.7% for myeloma, and 28.5% for leukemia.
Five-year survival for patients diagnosed in 1975-1977 was 46.5% for NHL, 24.6% for myeloma, and 34.2% for leukemia.
Five-year survival for patients diagnosed in 2006-2012 was 72.6% for NHL, 50.2% for myeloma, and 62.7% for leukemia.