Aggressive Lymphomas

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of selinexor (KPT-330) in patients with hematologic malignancies.

The partial hold, which was announced on March 10, was placed on all trials of the drug, including those in patients with solid tumor malignancies.

The hold meant that no new patients could be enrolled in selinexor trials.

Patients who were already enrolled and had stable disease or better could remain on selinexor therapy.

Now, the FDA has lifted the hold on trials of patients with hematologic malignancies, so new patients can be enrolled in these trials and begin receiving 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.

Karyopharm Therapeutics Inc., the company developing selinexor, noted that the hold was not the result of patient deaths or any new information regarding the safety profile of selinexor.

In response to the hold, Karyopharm amended the investigator’s brochure, updated informed consent documents, and submitted the documents to the FDA.

“The Karyopharm team worked diligently to update and submit the required documents to the FDA, which allowed the hematology division to expeditiously remove the partial clinical hold,” said Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm.

“We anticipate that the solid tumor divisions will follow suit shortly. Patient enrollment is again underway in our hematologic oncology studies. Our previously disclosed enrollment rates and timelines for both ongoing and planned trials are not expected to be materially impacted.”

About selinexor

Selinexor is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.

To date, more than 1900 patients have been treated with selinexor.

The drug is currently being evaluated in clinical trials across multiple cancer indications, including in acute myeloid leukemia (SOPRA), in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), as well as in diffuse large B-cell lymphoma (SADAL). 

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of selinexor (KPT-330) in patients with hematologic malignancies.

The partial hold, which was announced on March 10, was placed on all trials of the drug, including those in patients with solid tumor malignancies.

The hold meant that no new patients could be enrolled in selinexor trials.

Patients who were already enrolled and had stable disease or better could remain on selinexor therapy.

Now, the FDA has lifted the hold on trials of patients with hematologic malignancies, so new patients can be enrolled in these trials and begin receiving 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.

Karyopharm Therapeutics Inc., the company developing selinexor, noted that the hold was not the result of patient deaths or any new information regarding the safety profile of selinexor.

In response to the hold, Karyopharm amended the investigator’s brochure, updated informed consent documents, and submitted the documents to the FDA.

“The Karyopharm team worked diligently to update and submit the required documents to the FDA, which allowed the hematology division to expeditiously remove the partial clinical hold,” said Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm.

“We anticipate that the solid tumor divisions will follow suit shortly. Patient enrollment is again underway in our hematologic oncology studies. Our previously disclosed enrollment rates and timelines for both ongoing and planned trials are not expected to be materially impacted.”

About selinexor

Selinexor is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.

To date, more than 1900 patients have been treated with selinexor.

The drug is currently being evaluated in clinical trials across multiple cancer indications, including in acute myeloid leukemia (SOPRA), in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), as well as in diffuse large B-cell lymphoma (SADAL). 

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of selinexor (KPT-330) in patients with hematologic malignancies.

The partial hold, which was announced on March 10, was placed on all trials of the drug, including those in patients with solid tumor malignancies.

The hold meant that no new patients could be enrolled in selinexor trials.

Patients who were already enrolled and had stable disease or better could remain on selinexor therapy.

Now, the FDA has lifted the hold on trials of patients with hematologic malignancies, so new patients can be enrolled in these trials and begin receiving 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.

Karyopharm Therapeutics Inc., the company developing selinexor, noted that the hold was not the result of patient deaths or any new information regarding the safety profile of selinexor.

In response to the hold, Karyopharm amended the investigator’s brochure, updated informed consent documents, and submitted the documents to the FDA.

“The Karyopharm team worked diligently to update and submit the required documents to the FDA, which allowed the hematology division to expeditiously remove the partial clinical hold,” said Michael G. Kauffman, MD, PhD, chief executive officer of Karyopharm.

“We anticipate that the solid tumor divisions will follow suit shortly. Patient enrollment is again underway in our hematologic oncology studies. Our previously disclosed enrollment rates and timelines for both ongoing and planned trials are not expected to be materially impacted.”

About selinexor

Selinexor is a first-in-class, oral, selective inhibitor of nuclear export compound. The drug functions by inhibiting the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is thought to prompt apoptosis in cancer cells while largely sparing normal cells.

To date, more than 1900 patients have been treated with selinexor.

The drug is currently being evaluated in clinical trials across multiple cancer indications, including in acute myeloid leukemia (SOPRA), in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), as well as in diffuse large B-cell lymphoma (SADAL). 

 

Photo courtesy of Janssen

 

The phase 2 CARINA study of daratumumab in non-Hodgkin lymphoma (NHL) will not proceed to stage 2, according to Genmab A/S and Janssen Biotech, Inc.

 

In this study, researchers have been investigating daratumumab monotherapy in patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), or mantle cell lymphoma (MCL).

 

Researchers planned to enroll up to 210 patients in this trial in 2 stages. Stage 1 was designed to provide a preliminary assessment of activity.

 

The goal of stage 2 was to further evaluate the safety and efficacy of daratumumab in the 3 patient groups.

 

Stage 2 will not proceed because a data review showed the FL and DLBCL cohorts did not reach the predefined futility thresholds, which were overall response rates of 50% and 30%, respectively. In the MCL cohort, the overall response rate was not evaluable due to slow recruitment.

 

The decision regarding this study has no impact on other ongoing or planned studies with daratumumab.

 

“While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

 

“Daratumumab is still being investigated in a number of indications, including multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.”

 

About daratumumab

 

Daratumumab is a human IgG1k monoclonal antibody that binds to the CD38 molecule.

 

In the US, daratumumab is approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

 

Daratumumab monotherapy is approved in the US for patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

 

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

 

Photo courtesy of Janssen

 

The phase 2 CARINA study of daratumumab in non-Hodgkin lymphoma (NHL) will not proceed to stage 2, according to Genmab A/S and Janssen Biotech, Inc.

 

In this study, researchers have been investigating daratumumab monotherapy in patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), or mantle cell lymphoma (MCL).

 

Researchers planned to enroll up to 210 patients in this trial in 2 stages. Stage 1 was designed to provide a preliminary assessment of activity.

 

The goal of stage 2 was to further evaluate the safety and efficacy of daratumumab in the 3 patient groups.

 

Stage 2 will not proceed because a data review showed the FL and DLBCL cohorts did not reach the predefined futility thresholds, which were overall response rates of 50% and 30%, respectively. In the MCL cohort, the overall response rate was not evaluable due to slow recruitment.

 

The decision regarding this study has no impact on other ongoing or planned studies with daratumumab.

 

“While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

 

“Daratumumab is still being investigated in a number of indications, including multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.”

 

About daratumumab

 

Daratumumab is a human IgG1k monoclonal antibody that binds to the CD38 molecule.

 

In the US, daratumumab is approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

 

Daratumumab monotherapy is approved in the US for patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

 

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

 

Photo courtesy of Janssen

 

The phase 2 CARINA study of daratumumab in non-Hodgkin lymphoma (NHL) will not proceed to stage 2, according to Genmab A/S and Janssen Biotech, Inc.

 

In this study, researchers have been investigating daratumumab monotherapy in patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), or mantle cell lymphoma (MCL).

 

Researchers planned to enroll up to 210 patients in this trial in 2 stages. Stage 1 was designed to provide a preliminary assessment of activity.

 

The goal of stage 2 was to further evaluate the safety and efficacy of daratumumab in the 3 patient groups.

 

Stage 2 will not proceed because a data review showed the FL and DLBCL cohorts did not reach the predefined futility thresholds, which were overall response rates of 50% and 30%, respectively. In the MCL cohort, the overall response rate was not evaluable due to slow recruitment.

 

The decision regarding this study has no impact on other ongoing or planned studies with daratumumab.

 

“While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

 

“Daratumumab is still being investigated in a number of indications, including multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.”

 

About daratumumab

 

Daratumumab is a human IgG1k monoclonal antibody that binds to the CD38 molecule.

 

In the US, daratumumab is approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

 

Daratumumab monotherapy is approved in the US for patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

 

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

 

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

 

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

Photo courtesy of Merck

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for the anti-PD-1 therapy pembrolizumab (Keytruda) as a treatment for patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

The recommendation pertains specifically to adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV) or adults with cHL who are transplant-ineligible and have failed treatment with BV.

The CHMP’s recommendation will be reviewed by the European Commission, which is expected to make a decision about the drug in the second quarter of 2017.

Pembrolizumab is already approved for use in the European Union as a treatment for melanoma and non-small-cell lung cancer.

The CHMP’s positive opinion of pembrolizumab for cHL was based on data from the KEYNOTE-087 and KEYNOTE-013 trials. Results from both trials were presented at ASH 2016 (abstract 1107 and abstract 1108).

KEYNOTE-087

KEYNOTE-087 is a phase 2 trial in which researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%. Nineteen percent of patients achieved a CR, 39% had a PR, and 23% had SD.

The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median progression-free survival (PFS) was 11.4 months (range, 4.9-27.8 months). The six-month PFS rate was 66%, and the 12-month PFS rate was 48%.

 

The median overall survival was not reached. Six-month and 12-month overall survival rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

Photo by Nina Matthews

Women diagnosed with cancer during their childbearing years have an increased risk of preterm births, according to research published in JAMA Oncology.

The study showed that cancer survivors were more likely than women who never had cancer to give birth prematurely, have underweight babies, and undergo cesarean section deliveries.

The researchers said women diagnosed with cancer during pregnancy may be delivering early in order to start their cancer treatment, but that does not fully explain these findings.

The team also detected an increased risk of preterm delivery in women who had already received cancer treatment.

“We found that women were more likely to deliver preterm if they’ve been treated for cancer overall, with greater risks for women who had chemotherapy,” said study author Hazel B. Nichols, PhD, of University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.

“While we believe these findings are something women should be aware of, we still have a lot of work to do to understand why this risk is becoming apparent and whether or not the children who are born preterm to these women go on to develop any health concerns.”

Dr Nichols and her colleagues analyzed data on 2598 births to female adolescent and young adult cancer survivors (ages 15 to 39) and 12,990 births to women without a cancer diagnosis.

Among cancer survivors, there was a significantly increased prevalence of preterm birth (prevalence ratio [PR]=1.52), low birth weight (PR=1.59), and cesarean delivery (PR=1.08), compared to women without a cancer diagnosis.

Timing of diagnosis and cancer type

When the researchers broke the data down by cancer diagnosis, they found a higher risk of preterm birth and low birth weight for women with lymphoma as well as breast and gynecologic cancers.

The PR for preterm birth was 1.59 for Hodgkin lymphoma, 1.98 for breast cancer, 2.11 for non-Hodgkin lymphoma, and 2.58 for gynecologic cancer. The PR for low birth weight was 1.59 for breast cancer, 2.41 for non-Hodgkin lymphoma, and 2.74 for gynecologic cancer.

The researchers found an increased risk of adverse birth outcomes among women who were diagnosed with cancer while pregnant and before pregnancy.

Among women diagnosed while pregnant, the PR was 2.97 for preterm birth, 2.82 for low birth weight, 1.21 for cesarean delivery, and 1.90 for low Apgar score. Among women diagnosed before pregnancy, the PR was 1.23 for preterm birth and 1.36 for low birth weight.

Role of treatment

Compared to women without a cancer diagnosis, cancer survivors who received chemotherapy but no radiation were more likely to have preterm births (PR=2.11), infants with low birth weight (PR=2.36), and cesarean deliveries (PR=1.16).

There was no significant increase in adverse birth outcomes among cancer survivors who received radiation but not chemotherapy.

Among the cancer survivors, women who received chemotherapy without radiation were more likely to have preterm births (PR=2.12), infants with low birth weight (PR=2.13), and infants who were small for their gestational age (PR=1.43) when compared to women treated with surgery only.

Dr Nichols said the role of treatment is an area of possible future research.

“We’d like to get better information about the types of chemotherapy women receive,” she said. “Chemotherapy is a very broad category, and the agents have very different effects on the body. In the future, we’d like to get more detailed information on the types of drugs that were involved in treatment.”

Photo by Nina Matthews

Women diagnosed with cancer during their childbearing years have an increased risk of preterm births, according to research published in JAMA Oncology.

The study showed that cancer survivors were more likely than women who never had cancer to give birth prematurely, have underweight babies, and undergo cesarean section deliveries.

The researchers said women diagnosed with cancer during pregnancy may be delivering early in order to start their cancer treatment, but that does not fully explain these findings.

The team also detected an increased risk of preterm delivery in women who had already received cancer treatment.

“We found that women were more likely to deliver preterm if they’ve been treated for cancer overall, with greater risks for women who had chemotherapy,” said study author Hazel B. Nichols, PhD, of University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.

“While we believe these findings are something women should be aware of, we still have a lot of work to do to understand why this risk is becoming apparent and whether or not the children who are born preterm to these women go on to develop any health concerns.”

Dr Nichols and her colleagues analyzed data on 2598 births to female adolescent and young adult cancer survivors (ages 15 to 39) and 12,990 births to women without a cancer diagnosis.

Among cancer survivors, there was a significantly increased prevalence of preterm birth (prevalence ratio [PR]=1.52), low birth weight (PR=1.59), and cesarean delivery (PR=1.08), compared to women without a cancer diagnosis.

Timing of diagnosis and cancer type

When the researchers broke the data down by cancer diagnosis, they found a higher risk of preterm birth and low birth weight for women with lymphoma as well as breast and gynecologic cancers.

The PR for preterm birth was 1.59 for Hodgkin lymphoma, 1.98 for breast cancer, 2.11 for non-Hodgkin lymphoma, and 2.58 for gynecologic cancer. The PR for low birth weight was 1.59 for breast cancer, 2.41 for non-Hodgkin lymphoma, and 2.74 for gynecologic cancer.

The researchers found an increased risk of adverse birth outcomes among women who were diagnosed with cancer while pregnant and before pregnancy.

Among women diagnosed while pregnant, the PR was 2.97 for preterm birth, 2.82 for low birth weight, 1.21 for cesarean delivery, and 1.90 for low Apgar score. Among women diagnosed before pregnancy, the PR was 1.23 for preterm birth and 1.36 for low birth weight.

Role of treatment

Compared to women without a cancer diagnosis, cancer survivors who received chemotherapy but no radiation were more likely to have preterm births (PR=2.11), infants with low birth weight (PR=2.36), and cesarean deliveries (PR=1.16).

There was no significant increase in adverse birth outcomes among cancer survivors who received radiation but not chemotherapy.

Among the cancer survivors, women who received chemotherapy without radiation were more likely to have preterm births (PR=2.12), infants with low birth weight (PR=2.13), and infants who were small for their gestational age (PR=1.43) when compared to women treated with surgery only.

Dr Nichols said the role of treatment is an area of possible future research.

“We’d like to get better information about the types of chemotherapy women receive,” she said. “Chemotherapy is a very broad category, and the agents have very different effects on the body. In the future, we’d like to get more detailed information on the types of drugs that were involved in treatment.”

Photo by Nina Matthews

Women diagnosed with cancer during their childbearing years have an increased risk of preterm births, according to research published in JAMA Oncology.

The study showed that cancer survivors were more likely than women who never had cancer to give birth prematurely, have underweight babies, and undergo cesarean section deliveries.

The researchers said women diagnosed with cancer during pregnancy may be delivering early in order to start their cancer treatment, but that does not fully explain these findings.

The team also detected an increased risk of preterm delivery in women who had already received cancer treatment.

“We found that women were more likely to deliver preterm if they’ve been treated for cancer overall, with greater risks for women who had chemotherapy,” said study author Hazel B. Nichols, PhD, of University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.

“While we believe these findings are something women should be aware of, we still have a lot of work to do to understand why this risk is becoming apparent and whether or not the children who are born preterm to these women go on to develop any health concerns.”

Dr Nichols and her colleagues analyzed data on 2598 births to female adolescent and young adult cancer survivors (ages 15 to 39) and 12,990 births to women without a cancer diagnosis.

Among cancer survivors, there was a significantly increased prevalence of preterm birth (prevalence ratio [PR]=1.52), low birth weight (PR=1.59), and cesarean delivery (PR=1.08), compared to women without a cancer diagnosis.

Timing of diagnosis and cancer type

When the researchers broke the data down by cancer diagnosis, they found a higher risk of preterm birth and low birth weight for women with lymphoma as well as breast and gynecologic cancers.

The PR for preterm birth was 1.59 for Hodgkin lymphoma, 1.98 for breast cancer, 2.11 for non-Hodgkin lymphoma, and 2.58 for gynecologic cancer. The PR for low birth weight was 1.59 for breast cancer, 2.41 for non-Hodgkin lymphoma, and 2.74 for gynecologic cancer.

The researchers found an increased risk of adverse birth outcomes among women who were diagnosed with cancer while pregnant and before pregnancy.

Among women diagnosed while pregnant, the PR was 2.97 for preterm birth, 2.82 for low birth weight, 1.21 for cesarean delivery, and 1.90 for low Apgar score. Among women diagnosed before pregnancy, the PR was 1.23 for preterm birth and 1.36 for low birth weight.

Role of treatment

Compared to women without a cancer diagnosis, cancer survivors who received chemotherapy but no radiation were more likely to have preterm births (PR=2.11), infants with low birth weight (PR=2.36), and cesarean deliveries (PR=1.16).

There was no significant increase in adverse birth outcomes among cancer survivors who received radiation but not chemotherapy.

Among the cancer survivors, women who received chemotherapy without radiation were more likely to have preterm births (PR=2.12), infants with low birth weight (PR=2.13), and infants who were small for their gestational age (PR=1.43) when compared to women treated with surgery only.

Dr Nichols said the role of treatment is an area of possible future research.

“We’d like to get better information about the types of chemotherapy women receive,” she said. “Chemotherapy is a very broad category, and the agents have very different effects on the body. In the future, we’d like to get more detailed information on the types of drugs that were involved in treatment.”

 

Micrograph showing diffuse large B-cell lymphoma

 

When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.

 

In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.

 

Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.

 

This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.

 

Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.

 

Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.

 

The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).

 

Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.

 

Response

 

The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).

 

Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.

 

Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.

 

Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.

 

The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).

 

The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).

 

High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).

 

Toxicity

 

Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).

 

The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.

 

One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.

 

One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.

 

The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).

 

In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).

 

Micrograph showing diffuse large B-cell lymphoma

 

When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.

 

In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.

 

Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.

 

This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.

 

Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.

 

Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.

 

The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).

 

Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.

 

Response

 

The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).

 

Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.

 

Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.

 

Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.

 

The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).

 

The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).

 

High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).

 

Toxicity

 

Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).

 

The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.

 

One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.

 

One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.

 

The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).

 

In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).

 

Micrograph showing diffuse large B-cell lymphoma

 

When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.

 

In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.

 

Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.

 

This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.

 

Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.

 

Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.

 

The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).

 

Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.

 

Response

 

The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).

 

Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.

 

Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.

 

Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.

 

The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).

 

The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).

 

High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).

 

Toxicity

 

Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).

 

The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.

 

One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.

 

One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.

 

The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).

 

In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).

 

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

The complete remission rate was 22% and the partial remission rate was 47%. The median follow-up time in the study was 9.4 months.

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center, New York, said in the press release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis.”

According to Merck, continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The revised drug label information can be found here.

[email protected]

 

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

The complete remission rate was 22% and the partial remission rate was 47%. The median follow-up time in the study was 9.4 months.

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center, New York, said in the press release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis.”

According to Merck, continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The revised drug label information can be found here.

[email protected]

 

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

The complete remission rate was 22% and the partial remission rate was 47%. The median follow-up time in the study was 9.4 months.

“For the patients with classical Hodgkin lymphoma who are not cured with existing treatments, there are limited options, and treating their disease becomes more challenging,” Craig H. Moskowitz, MD, clinical director of the division of hematologic oncology at Memorial Sloan Kettering Cancer Center, New York, said in the press release. “This approval is an important step forward in treating these patients, who are generally young and have a particularly poor prognosis.”

According to Merck, continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The revised drug label information can be found here.

[email protected]

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo by Rhoda Baer

A new study suggests Hodgkin lymphoma (HL) survivors have a high risk of developing a second malignancy, particularly if they have a family history of that malignancy.

The research showed that HL survivors in Sweden were roughly 2.4 times more likely than individuals in the country’s general population to develop a second cancer.

The risk for HL survivors remained high 30 years after treatment, and the risk was even greater in HL survivors who had a family history of specific cancers.

“The vast majority of patients with Hodgkin lymphoma are cured with a combination of chemotherapy and radiotherapy,” said study author Amit Sud, MBChB, of The Institute of Cancer Research, London in the UK.

“Our research has shown that these patients are at substantially increased risk of a second cancer later in life and particularly if they have a family history of cancer.”

Dr Sud and his colleagues described this research in the Journal of Clinical Oncology.

The team analyzed data from the Swedish Family-Cancer Project Database. They identified 9522 HL patients diagnosed between 1965 and 2013. During a median follow-up of 12.6 years, there were 1215 second cancers in 1121 HL patients (12%).

Compared to the general population, the HL patients had a significantly higher risk of all second malignancies, with a standardized incident ratio (SIR) of 2.39 and an absolute excess risk of 71.2 cases per 10,000 person-years.

Cancer types

HL patients had a significantly increased risk of several malignancies. The overall SIRs were as follows:

• NHL—7.99
• Leukemia—6.46
• Connective tissue cancer—5.73
• Thyroid cancer—5.13
• Squamous cell carcinoma—4.44
• Lung cancer—3.61
• Pharyngeal cancer—3.52
• Esophageal cancer—2.62
• Brain cancer—2.58
• Breast cancer—2.52
• Colon cancer—2.21
• Pancreatic cancer—2.09
• Melanoma—2.08
• Colorectal cancer—1.85
• Stomach cancer—1.78
• Bladder cancer—1.57
• Prostate cancer—1.21.

The researchers calculated SIRs over time and found the risk for many of the cancers remained high over 30 years following HL treatment.

Family history

The researchers identified 28,277 first-degree relatives of the HL survivors. Thirty percent of HL survivors (n=2785) had 1 or more first-degree relatives with a family history of cancer.

The SIR for cancers was 1.02 in the relatives. The SIR for second cancers was 2.83 for HL survivors who had first-degree relatives with cancer and 2.16 for HL survivors who did not have any first-degree relatives with cancer.

The researchers said the increased risk of second malignancy was correlated with the number of first-degree relatives with cancer.

The SIR was 2.67 for HL patients who had a single first-degree relative with cancer and 3.40 for HL patients who had 2 or more first-degree relatives with cancer.

The SIRs for different cancer types (for HL patients with at least 1 first-degree relative with cancer and no first-degree relatives with cancer, respectively) were as follows:

• NHL—14.43 vs 7.83
• Leukemia—14.31 vs 6.37
• Squamous cell carcinoma—10.85 vs 4.30
• Lung cancer—11.24 vs 3.39
• Breast cancer—4.36 vs 2.36
• Colorectal cancer—3.71 vs 1.76.

Sex and age

The researchers found significant differences in the SIRs for second cancers between HL patients diagnosed before the age of 35 and those diagnosed after age 35.

For men, the SIRs were:

• All cancers—4.26 for <35, 2.08 for ≥ 35
• Colorectal cancer—4.07 for < 35, 1.73 for ≥35
• Lung cancer—6.16 for < 35, 3.20 for ≥35
• Breast cancer—12.60 for < 35, 4.58 for ≥35
• Squamous cell carcinoma—5.89 for < 35, 3.96 for ≥35
• NHL—15.9 for < 35, 6.93 for ≥35
• Leukemia—12.15 for < 35, 5.57 for ≥35.

For women, the SIRs were:

• All cancers—4.61 for <35, 1.73 for ≥ 35
• Colorectal cancer—1.31 for < 35, 1.65 for ≥35
• Lung cancer—8.84 for < 35, 2.50 for ≥35
• Breast cancer—6.00 for < 35, 1.14 for ≥35
• Squamous cell carcinoma—6.37 for < 35, 4.87 for ≥35
• NHL—6.23 for < 35, 6.55 for ≥35
• Leukemia—10.36 for < 35, 4.51 for ≥35.

 

“Younger women who have been treated with radiotherapy to the chest for Hodgkin lymphoma are already screened for breast cancer, but our study suggests that we should be looking at ways of monitoring survivors for other forms of cancer too, and potentially offering preventative interventions,” Dr Sud said.

“After patients are cured, they no longer encounter oncologists, so it’s important that other healthcare providers are aware of the increased risk to Hodgkin lymphoma survivors to improve early diagnosis of second cancers.”

Photo by Rhoda Baer

A new study suggests Hodgkin lymphoma (HL) survivors have a high risk of developing a second malignancy, particularly if they have a family history of that malignancy.

The research showed that HL survivors in Sweden were roughly 2.4 times more likely than individuals in the country’s general population to develop a second cancer.

The risk for HL survivors remained high 30 years after treatment, and the risk was even greater in HL survivors who had a family history of specific cancers.

“The vast majority of patients with Hodgkin lymphoma are cured with a combination of chemotherapy and radiotherapy,” said study author Amit Sud, MBChB, of The Institute of Cancer Research, London in the UK.

“Our research has shown that these patients are at substantially increased risk of a second cancer later in life and particularly if they have a family history of cancer.”

Dr Sud and his colleagues described this research in the Journal of Clinical Oncology.

The team analyzed data from the Swedish Family-Cancer Project Database. They identified 9522 HL patients diagnosed between 1965 and 2013. During a median follow-up of 12.6 years, there were 1215 second cancers in 1121 HL patients (12%).

Compared to the general population, the HL patients had a significantly higher risk of all second malignancies, with a standardized incident ratio (SIR) of 2.39 and an absolute excess risk of 71.2 cases per 10,000 person-years.

Cancer types

HL patients had a significantly increased risk of several malignancies. The overall SIRs were as follows:

• NHL—7.99
• Leukemia—6.46
• Connective tissue cancer—5.73
• Thyroid cancer—5.13
• Squamous cell carcinoma—4.44
• Lung cancer—3.61
• Pharyngeal cancer—3.52
• Esophageal cancer—2.62
• Brain cancer—2.58
• Breast cancer—2.52
• Colon cancer—2.21
• Pancreatic cancer—2.09
• Melanoma—2.08
• Colorectal cancer—1.85
• Stomach cancer—1.78
• Bladder cancer—1.57
• Prostate cancer—1.21.

The researchers calculated SIRs over time and found the risk for many of the cancers remained high over 30 years following HL treatment.

Family history

The researchers identified 28,277 first-degree relatives of the HL survivors. Thirty percent of HL survivors (n=2785) had 1 or more first-degree relatives with a family history of cancer.

The SIR for cancers was 1.02 in the relatives. The SIR for second cancers was 2.83 for HL survivors who had first-degree relatives with cancer and 2.16 for HL survivors who did not have any first-degree relatives with cancer.

The researchers said the increased risk of second malignancy was correlated with the number of first-degree relatives with cancer.

The SIR was 2.67 for HL patients who had a single first-degree relative with cancer and 3.40 for HL patients who had 2 or more first-degree relatives with cancer.

The SIRs for different cancer types (for HL patients with at least 1 first-degree relative with cancer and no first-degree relatives with cancer, respectively) were as follows:

• NHL—14.43 vs 7.83
• Leukemia—14.31 vs 6.37
• Squamous cell carcinoma—10.85 vs 4.30
• Lung cancer—11.24 vs 3.39
• Breast cancer—4.36 vs 2.36
• Colorectal cancer—3.71 vs 1.76.

Sex and age

The researchers found significant differences in the SIRs for second cancers between HL patients diagnosed before the age of 35 and those diagnosed after age 35.

For men, the SIRs were:

• All cancers—4.26 for <35, 2.08 for ≥ 35
• Colorectal cancer—4.07 for < 35, 1.73 for ≥35
• Lung cancer—6.16 for < 35, 3.20 for ≥35
• Breast cancer—12.60 for < 35, 4.58 for ≥35
• Squamous cell carcinoma—5.89 for < 35, 3.96 for ≥35
• NHL—15.9 for < 35, 6.93 for ≥35
• Leukemia—12.15 for < 35, 5.57 for ≥35.

For women, the SIRs were:

• All cancers—4.61 for <35, 1.73 for ≥ 35
• Colorectal cancer—1.31 for < 35, 1.65 for ≥35
• Lung cancer—8.84 for < 35, 2.50 for ≥35
• Breast cancer—6.00 for < 35, 1.14 for ≥35
• Squamous cell carcinoma—6.37 for < 35, 4.87 for ≥35
• NHL—6.23 for < 35, 6.55 for ≥35
• Leukemia—10.36 for < 35, 4.51 for ≥35.

 

“Younger women who have been treated with radiotherapy to the chest for Hodgkin lymphoma are already screened for breast cancer, but our study suggests that we should be looking at ways of monitoring survivors for other forms of cancer too, and potentially offering preventative interventions,” Dr Sud said.

“After patients are cured, they no longer encounter oncologists, so it’s important that other healthcare providers are aware of the increased risk to Hodgkin lymphoma survivors to improve early diagnosis of second cancers.”

Photo by Rhoda Baer

A new study suggests Hodgkin lymphoma (HL) survivors have a high risk of developing a second malignancy, particularly if they have a family history of that malignancy.

The research showed that HL survivors in Sweden were roughly 2.4 times more likely than individuals in the country’s general population to develop a second cancer.

The risk for HL survivors remained high 30 years after treatment, and the risk was even greater in HL survivors who had a family history of specific cancers.

“The vast majority of patients with Hodgkin lymphoma are cured with a combination of chemotherapy and radiotherapy,” said study author Amit Sud, MBChB, of The Institute of Cancer Research, London in the UK.

“Our research has shown that these patients are at substantially increased risk of a second cancer later in life and particularly if they have a family history of cancer.”

Dr Sud and his colleagues described this research in the Journal of Clinical Oncology.

The team analyzed data from the Swedish Family-Cancer Project Database. They identified 9522 HL patients diagnosed between 1965 and 2013. During a median follow-up of 12.6 years, there were 1215 second cancers in 1121 HL patients (12%).

Compared to the general population, the HL patients had a significantly higher risk of all second malignancies, with a standardized incident ratio (SIR) of 2.39 and an absolute excess risk of 71.2 cases per 10,000 person-years.

Cancer types

HL patients had a significantly increased risk of several malignancies. The overall SIRs were as follows:

• NHL—7.99
• Leukemia—6.46
• Connective tissue cancer—5.73
• Thyroid cancer—5.13
• Squamous cell carcinoma—4.44
• Lung cancer—3.61
• Pharyngeal cancer—3.52
• Esophageal cancer—2.62
• Brain cancer—2.58
• Breast cancer—2.52
• Colon cancer—2.21
• Pancreatic cancer—2.09
• Melanoma—2.08
• Colorectal cancer—1.85
• Stomach cancer—1.78
• Bladder cancer—1.57
• Prostate cancer—1.21.

The researchers calculated SIRs over time and found the risk for many of the cancers remained high over 30 years following HL treatment.

Family history

The researchers identified 28,277 first-degree relatives of the HL survivors. Thirty percent of HL survivors (n=2785) had 1 or more first-degree relatives with a family history of cancer.

The SIR for cancers was 1.02 in the relatives. The SIR for second cancers was 2.83 for HL survivors who had first-degree relatives with cancer and 2.16 for HL survivors who did not have any first-degree relatives with cancer.

The researchers said the increased risk of second malignancy was correlated with the number of first-degree relatives with cancer.

The SIR was 2.67 for HL patients who had a single first-degree relative with cancer and 3.40 for HL patients who had 2 or more first-degree relatives with cancer.

The SIRs for different cancer types (for HL patients with at least 1 first-degree relative with cancer and no first-degree relatives with cancer, respectively) were as follows:

• NHL—14.43 vs 7.83
• Leukemia—14.31 vs 6.37
• Squamous cell carcinoma—10.85 vs 4.30
• Lung cancer—11.24 vs 3.39
• Breast cancer—4.36 vs 2.36
• Colorectal cancer—3.71 vs 1.76.

Sex and age

The researchers found significant differences in the SIRs for second cancers between HL patients diagnosed before the age of 35 and those diagnosed after age 35.

For men, the SIRs were:

• All cancers—4.26 for <35, 2.08 for ≥ 35
• Colorectal cancer—4.07 for < 35, 1.73 for ≥35
• Lung cancer—6.16 for < 35, 3.20 for ≥35
• Breast cancer—12.60 for < 35, 4.58 for ≥35
• Squamous cell carcinoma—5.89 for < 35, 3.96 for ≥35
• NHL—15.9 for < 35, 6.93 for ≥35
• Leukemia—12.15 for < 35, 5.57 for ≥35.

For women, the SIRs were:

• All cancers—4.61 for <35, 1.73 for ≥ 35
• Colorectal cancer—1.31 for < 35, 1.65 for ≥35
• Lung cancer—8.84 for < 35, 2.50 for ≥35
• Breast cancer—6.00 for < 35, 1.14 for ≥35
• Squamous cell carcinoma—6.37 for < 35, 4.87 for ≥35
• NHL—6.23 for < 35, 6.55 for ≥35
• Leukemia—10.36 for < 35, 4.51 for ≥35.

 

“Younger women who have been treated with radiotherapy to the chest for Hodgkin lymphoma are already screened for breast cancer, but our study suggests that we should be looking at ways of monitoring survivors for other forms of cancer too, and potentially offering preventative interventions,” Dr Sud said.

“After patients are cured, they no longer encounter oncologists, so it’s important that other healthcare providers are aware of the increased risk to Hodgkin lymphoma survivors to improve early diagnosis of second cancers.”