Hodgkin Lymphoma

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

 

2016 ASH Annual Meeting
© Todd Buchanan 2016

 

SAN DIEGO—Immune checkpoint blockade with nivolumab plus ipilimumab has shown promise in treating hematologic malignancies, particularly classical Hodgkin lymphoma (HL), based on results of the combination cohort of the phase 1 CheckMate 039 study.

Thirty-one heavily pre-treated HL patients achieved an overall response rate (ORR) of 74%, including 6 complete responses.

And in transplant-naïve HL patients, the combination produced an ORR of 67%. 

“Most in the room would be familiar with the excellent results that we have seen with monotherapy with nivolumab,” Stephen Ansell, MD, PhD, of the Mayo Clinic in Rochester, Minnesota, said at the 2016 ASH Annual Meeting.

“In classical Hodgkin lymphoma, we’ve seen meaningful and clinically quite stellar results and durable responses.”

“Our plan was, as part of this trial [CheckMate 039], to then move to see whether adding a further checkpoint, ipilimumab, could enhance the results seen with nivolumab.”

Dr Ansell presented the findings for the checkpoint combination as abstract 183. He disclosed research funding from Bristol-Myers Squibb, the company that funded the study.
 
Checkpoint inhibitors

Nivolumab and ipilimumab are both fully human monoclonal antibodies, but ipilimumab “works in a slightly different fashion from nivolumab,” Dr Ansell said.

Nivolumab targets the programmed death receptor-1 (PD-1) and disrupts PD-1 pathway signaling and restores anti-tumor T-cell function.

Ipilimumab targets cytotoxic T-lymphocyte antigen 4 (CTLA-4) and induces anti-tumor immunity.

The combination has shown superior efficacy, compared to either agent alone, in preclinical studies and a phase 1 trial of patients with advanced melanoma.

So the investigators added a combination cohort to CheckMate 039.

Combination cohort study design

Patients were eligible to enroll if they had relapsed or refractory HL, B-cell non-Hodgkin lymphoma (NHL, including follicular or diffuse large B-cell lymphoma), T-cell NHL (including cutaneous or peripheral T-cell lymphoma), or multiple myeloma (MM).

Patients could not have had prior organ or allogeneic stem cell transplant and no prior immune checkpoint blockade therapy.

Treatment consisted of nivolumab at 3 mg/kg IV plus ipilimumab at 1 mg/kg IV every 3 weeks for 4 doses. The combination phase was followed by nivolumab monotherapy at the same dose every 2 weeks for 2 years.

The primary endpoint was safety and tolerability. Secondary endpoints included investigator-assessed best overall response, duration of response, progression-free survival (PFS), and biomarker analyses.

Patient characteristics

The investigators enrolled 31 HL, 15 B-cell NHL, 11 T-cell NHL, and 7 MM patients. Most patients, Dr Ansell noted, were heavily pretreated.

HL patients were 42% male, 52% had an ECOG status of 1, and they had a median of 4 (range, 2 to 10) prior systemic therapies. Forty-two percent had prior autologous stem cell transplant (ASCT).

“Interestingly, in the Hodgkin cohort, a number of patients had not proceeded to an autologous transplant, but predominantly because these were chemo-refractory or chemo-resistant patients not eligible for a transplant,” Dr Ansell pointed out.

Of the HL patients, 18 were transplant-naïve, 13 were chemo-resistant, 3 were ineligible for ASCT, and 2 declined the procedure.

B-cell NHL patients were 73% male, and 80% had an ECOG status of 1. They had a median of 3 (range, 1 to 16) prior systemic therapies. Seven percent had a prior ASCT.

T-cell NHL patients were 55% male, 73% had an ECOG status of 1, and they had a median of 4 (range, 1 to 11) prior systemic therapies. None had a prior ASCT.

MM patients were 86% male, 71% had an ECOG status of 1, and they had a median of 5 (range, 2 to 20) prior systemic therapies. More than half had a prior ASCT.

Patient disposition

With follow-up approaching a year, more patients with HL are still on treatment (39%) compared with B-cell NHL (13%), T-cell NHL (18%), and MM (0%) patients.

“Of note, however, is that the reasons for going off treatment were predominantly disease progression,” Dr Ansell said.

“The vast majority of patients who came off treatment came off treatment because their disease progressed, and the numbers that came off because of toxicity were relatively low.”

Seven HL patients went off treatment due to disease progression and 2 due to study drug toxicity.

Eleven B-cell NHL patients went off treatment due to disease progression and 2 withdrew due to unrelated adverse events (AEs).

Five T-cell NHL patients went off treatment due to disease progression and 2 due to study drug toxicity.

And 4 MM patients withdrew due to disease progression, 1 due to study drug toxicity, and 1 due to AEs unrelated to the study drug.

About two-thirds of HL patients, over 90% of B-cell NHL patients, about 80% of T-cell NHL patients, and about 70% of MM patients received 90% or more of the intended dose of each drug.

Safety

One patient with primary mediastinal B-cell lymphoma was included in the safety analysis, for a total of 65 patients treated.

“The majority of patients had some degree of adverse event,” Dr Ansell explained. “But if one looks at the grade 3 and 4 adverse events, those were seen in a more modest number of patients, in a minority of patients. And most importantly, if one looks at the adverse events that led to discontinuation, one can see that this was in a significant minority of patients.”

Five patients discontinued due to treatment-related AEs, which were pneumonitis (n=3), pneumonia and pneumonitis (n=1), and diabetic ketoacidosis (n=1).

Overall, 51 patients (78%) experienced an AE; 19 (29%) had a grade 3–4 AE, 14 (22%) had a serious AE, and 5 (8%) discontinued due to an AE.

Of 31 HL patients, 28 (90%) had an AE, 8 (26%) had a grade 3–4 AE, 6 (19%) had a serious AE, and 2 (6%) discontinued due to an AE.

All 11 T-cell NHL patients experienced an AE, 5 patients (45%) a grade 3-4 AE, 4 patients (36%) had a serious AE, and 2 patients (18%) discontinued because of an AE.

About half of B-cell NHL and MM patients experienced an AE, with 1 MM patient discontinuing as a result of it and no B-cell NHL patient discontinuing due to an AE.

“I would highlight that most of the adverse events were, as expected, immunological in nature . . . . ,” Dr Ansell said. “A very modest number of patients had grade 3 and 4 toxicities.”

The most common drug-related AEs of any grade were fatigue (n=17; 26%), pyrexia (n=15; 23%), rash (n=7; 11%), diarrhea (n=12; 18%), and nausea, pneumonitis, cough, and infusion-related reactions, with 9 patients each (14%).

Efficacy

Twenty-three HL patients (74%) achieved an overall response, including 6 patients (19%) with a complete response and 17 (55%) with a partial response. Three patients (10%) had stable disease, and 3 (10%) had relapsed or progressive disease. Response was not reported for 2 patients (6%).

“Most of these responses are durable, and, very encouraging, you can see patients out approaching a year continuing on therapy,” Dr Ansell said.

The ORR in the 18 transplant-naive patients was 67% (n=67).

The median duration of response for HL patients was not reached and ranged from 0.0 to 13.4 months.

B-cell NHL patients had an ORR of 20% (n=3). There were no complete responses and 3 (20%) partial responses. One patient (7%) had stable disease, and 8 (53%) had relapsed or progressive disase. The median duration of partial response was not reached and ranged from 11.0 to 12.7 months.

T-cell NHL patients had an ORR of 9% (n=1). There were no complete responses and 1 (9%) partial response. Four patients (36%) had stable disease, and 3 (27%) had relapsed or progressive disease. The median duration of partial response was not reached and was 3.9 months.

Except for 1 patient with stable disease, MM patients did not respond to therapy.

Biomarker analysis

All 19 HL patients with a known PD-L1 status at baseline saw their tumor burden decrease to below baseline levels. This may be because HL is characterized by high PD-L1 expression and high responsiveness to checkpoint blockade.

Patients with NHL, on the other hand, have a diverse group of tumors characterized by variable PD-L1 expression. Eight of 13 patients with known expression saw their tumor burden decrease with treatment to below baseline.

Encouraged by the results, the investigators believe further investigation of the combination is in order, as the combination, with limited follow-up, achieved a high and durable ORR in HL patients, including those who were transplant-naïve.

 

2016 ASH Annual Meeting
© Todd Buchanan 2016

 

SAN DIEGO—Immune checkpoint blockade with nivolumab plus ipilimumab has shown promise in treating hematologic malignancies, particularly classical Hodgkin lymphoma (HL), based on results of the combination cohort of the phase 1 CheckMate 039 study.

Thirty-one heavily pre-treated HL patients achieved an overall response rate (ORR) of 74%, including 6 complete responses.

And in transplant-naïve HL patients, the combination produced an ORR of 67%. 

“Most in the room would be familiar with the excellent results that we have seen with monotherapy with nivolumab,” Stephen Ansell, MD, PhD, of the Mayo Clinic in Rochester, Minnesota, said at the 2016 ASH Annual Meeting.

“In classical Hodgkin lymphoma, we’ve seen meaningful and clinically quite stellar results and durable responses.”

“Our plan was, as part of this trial [CheckMate 039], to then move to see whether adding a further checkpoint, ipilimumab, could enhance the results seen with nivolumab.”

Dr Ansell presented the findings for the checkpoint combination as abstract 183. He disclosed research funding from Bristol-Myers Squibb, the company that funded the study.
 
Checkpoint inhibitors

Nivolumab and ipilimumab are both fully human monoclonal antibodies, but ipilimumab “works in a slightly different fashion from nivolumab,” Dr Ansell said.

Nivolumab targets the programmed death receptor-1 (PD-1) and disrupts PD-1 pathway signaling and restores anti-tumor T-cell function.

Ipilimumab targets cytotoxic T-lymphocyte antigen 4 (CTLA-4) and induces anti-tumor immunity.

The combination has shown superior efficacy, compared to either agent alone, in preclinical studies and a phase 1 trial of patients with advanced melanoma.

So the investigators added a combination cohort to CheckMate 039.

Combination cohort study design

Patients were eligible to enroll if they had relapsed or refractory HL, B-cell non-Hodgkin lymphoma (NHL, including follicular or diffuse large B-cell lymphoma), T-cell NHL (including cutaneous or peripheral T-cell lymphoma), or multiple myeloma (MM).

Patients could not have had prior organ or allogeneic stem cell transplant and no prior immune checkpoint blockade therapy.

Treatment consisted of nivolumab at 3 mg/kg IV plus ipilimumab at 1 mg/kg IV every 3 weeks for 4 doses. The combination phase was followed by nivolumab monotherapy at the same dose every 2 weeks for 2 years.

The primary endpoint was safety and tolerability. Secondary endpoints included investigator-assessed best overall response, duration of response, progression-free survival (PFS), and biomarker analyses.

Patient characteristics

The investigators enrolled 31 HL, 15 B-cell NHL, 11 T-cell NHL, and 7 MM patients. Most patients, Dr Ansell noted, were heavily pretreated.

HL patients were 42% male, 52% had an ECOG status of 1, and they had a median of 4 (range, 2 to 10) prior systemic therapies. Forty-two percent had prior autologous stem cell transplant (ASCT).

“Interestingly, in the Hodgkin cohort, a number of patients had not proceeded to an autologous transplant, but predominantly because these were chemo-refractory or chemo-resistant patients not eligible for a transplant,” Dr Ansell pointed out.

Of the HL patients, 18 were transplant-naïve, 13 were chemo-resistant, 3 were ineligible for ASCT, and 2 declined the procedure.

B-cell NHL patients were 73% male, and 80% had an ECOG status of 1. They had a median of 3 (range, 1 to 16) prior systemic therapies. Seven percent had a prior ASCT.

T-cell NHL patients were 55% male, 73% had an ECOG status of 1, and they had a median of 4 (range, 1 to 11) prior systemic therapies. None had a prior ASCT.

MM patients were 86% male, 71% had an ECOG status of 1, and they had a median of 5 (range, 2 to 20) prior systemic therapies. More than half had a prior ASCT.

Patient disposition

With follow-up approaching a year, more patients with HL are still on treatment (39%) compared with B-cell NHL (13%), T-cell NHL (18%), and MM (0%) patients.

“Of note, however, is that the reasons for going off treatment were predominantly disease progression,” Dr Ansell said.

“The vast majority of patients who came off treatment came off treatment because their disease progressed, and the numbers that came off because of toxicity were relatively low.”

Seven HL patients went off treatment due to disease progression and 2 due to study drug toxicity.

Eleven B-cell NHL patients went off treatment due to disease progression and 2 withdrew due to unrelated adverse events (AEs).

Five T-cell NHL patients went off treatment due to disease progression and 2 due to study drug toxicity.

And 4 MM patients withdrew due to disease progression, 1 due to study drug toxicity, and 1 due to AEs unrelated to the study drug.

About two-thirds of HL patients, over 90% of B-cell NHL patients, about 80% of T-cell NHL patients, and about 70% of MM patients received 90% or more of the intended dose of each drug.

Safety

One patient with primary mediastinal B-cell lymphoma was included in the safety analysis, for a total of 65 patients treated.

“The majority of patients had some degree of adverse event,” Dr Ansell explained. “But if one looks at the grade 3 and 4 adverse events, those were seen in a more modest number of patients, in a minority of patients. And most importantly, if one looks at the adverse events that led to discontinuation, one can see that this was in a significant minority of patients.”

Five patients discontinued due to treatment-related AEs, which were pneumonitis (n=3), pneumonia and pneumonitis (n=1), and diabetic ketoacidosis (n=1).

Overall, 51 patients (78%) experienced an AE; 19 (29%) had a grade 3–4 AE, 14 (22%) had a serious AE, and 5 (8%) discontinued due to an AE.

Of 31 HL patients, 28 (90%) had an AE, 8 (26%) had a grade 3–4 AE, 6 (19%) had a serious AE, and 2 (6%) discontinued due to an AE.

All 11 T-cell NHL patients experienced an AE, 5 patients (45%) a grade 3-4 AE, 4 patients (36%) had a serious AE, and 2 patients (18%) discontinued because of an AE.

About half of B-cell NHL and MM patients experienced an AE, with 1 MM patient discontinuing as a result of it and no B-cell NHL patient discontinuing due to an AE.

“I would highlight that most of the adverse events were, as expected, immunological in nature . . . . ,” Dr Ansell said. “A very modest number of patients had grade 3 and 4 toxicities.”

The most common drug-related AEs of any grade were fatigue (n=17; 26%), pyrexia (n=15; 23%), rash (n=7; 11%), diarrhea (n=12; 18%), and nausea, pneumonitis, cough, and infusion-related reactions, with 9 patients each (14%).

Efficacy

Twenty-three HL patients (74%) achieved an overall response, including 6 patients (19%) with a complete response and 17 (55%) with a partial response. Three patients (10%) had stable disease, and 3 (10%) had relapsed or progressive disease. Response was not reported for 2 patients (6%).

“Most of these responses are durable, and, very encouraging, you can see patients out approaching a year continuing on therapy,” Dr Ansell said.

The ORR in the 18 transplant-naive patients was 67% (n=67).

The median duration of response for HL patients was not reached and ranged from 0.0 to 13.4 months.

B-cell NHL patients had an ORR of 20% (n=3). There were no complete responses and 3 (20%) partial responses. One patient (7%) had stable disease, and 8 (53%) had relapsed or progressive disase. The median duration of partial response was not reached and ranged from 11.0 to 12.7 months.

T-cell NHL patients had an ORR of 9% (n=1). There were no complete responses and 1 (9%) partial response. Four patients (36%) had stable disease, and 3 (27%) had relapsed or progressive disease. The median duration of partial response was not reached and was 3.9 months.

Except for 1 patient with stable disease, MM patients did not respond to therapy.

Biomarker analysis

All 19 HL patients with a known PD-L1 status at baseline saw their tumor burden decrease to below baseline levels. This may be because HL is characterized by high PD-L1 expression and high responsiveness to checkpoint blockade.

Patients with NHL, on the other hand, have a diverse group of tumors characterized by variable PD-L1 expression. Eight of 13 patients with known expression saw their tumor burden decrease with treatment to below baseline.

Encouraged by the results, the investigators believe further investigation of the combination is in order, as the combination, with limited follow-up, achieved a high and durable ORR in HL patients, including those who were transplant-naïve.

 

2016 ASH Annual Meeting
© Todd Buchanan 2016

 

SAN DIEGO—Immune checkpoint blockade with nivolumab plus ipilimumab has shown promise in treating hematologic malignancies, particularly classical Hodgkin lymphoma (HL), based on results of the combination cohort of the phase 1 CheckMate 039 study.

Thirty-one heavily pre-treated HL patients achieved an overall response rate (ORR) of 74%, including 6 complete responses.

And in transplant-naïve HL patients, the combination produced an ORR of 67%. 

“Most in the room would be familiar with the excellent results that we have seen with monotherapy with nivolumab,” Stephen Ansell, MD, PhD, of the Mayo Clinic in Rochester, Minnesota, said at the 2016 ASH Annual Meeting.

“In classical Hodgkin lymphoma, we’ve seen meaningful and clinically quite stellar results and durable responses.”

“Our plan was, as part of this trial [CheckMate 039], to then move to see whether adding a further checkpoint, ipilimumab, could enhance the results seen with nivolumab.”

Dr Ansell presented the findings for the checkpoint combination as abstract 183. He disclosed research funding from Bristol-Myers Squibb, the company that funded the study.
 
Checkpoint inhibitors

Nivolumab and ipilimumab are both fully human monoclonal antibodies, but ipilimumab “works in a slightly different fashion from nivolumab,” Dr Ansell said.

Nivolumab targets the programmed death receptor-1 (PD-1) and disrupts PD-1 pathway signaling and restores anti-tumor T-cell function.

Ipilimumab targets cytotoxic T-lymphocyte antigen 4 (CTLA-4) and induces anti-tumor immunity.

The combination has shown superior efficacy, compared to either agent alone, in preclinical studies and a phase 1 trial of patients with advanced melanoma.

So the investigators added a combination cohort to CheckMate 039.

Combination cohort study design

Patients were eligible to enroll if they had relapsed or refractory HL, B-cell non-Hodgkin lymphoma (NHL, including follicular or diffuse large B-cell lymphoma), T-cell NHL (including cutaneous or peripheral T-cell lymphoma), or multiple myeloma (MM).

Patients could not have had prior organ or allogeneic stem cell transplant and no prior immune checkpoint blockade therapy.

Treatment consisted of nivolumab at 3 mg/kg IV plus ipilimumab at 1 mg/kg IV every 3 weeks for 4 doses. The combination phase was followed by nivolumab monotherapy at the same dose every 2 weeks for 2 years.

The primary endpoint was safety and tolerability. Secondary endpoints included investigator-assessed best overall response, duration of response, progression-free survival (PFS), and biomarker analyses.

Patient characteristics

The investigators enrolled 31 HL, 15 B-cell NHL, 11 T-cell NHL, and 7 MM patients. Most patients, Dr Ansell noted, were heavily pretreated.

HL patients were 42% male, 52% had an ECOG status of 1, and they had a median of 4 (range, 2 to 10) prior systemic therapies. Forty-two percent had prior autologous stem cell transplant (ASCT).

“Interestingly, in the Hodgkin cohort, a number of patients had not proceeded to an autologous transplant, but predominantly because these were chemo-refractory or chemo-resistant patients not eligible for a transplant,” Dr Ansell pointed out.

Of the HL patients, 18 were transplant-naïve, 13 were chemo-resistant, 3 were ineligible for ASCT, and 2 declined the procedure.

B-cell NHL patients were 73% male, and 80% had an ECOG status of 1. They had a median of 3 (range, 1 to 16) prior systemic therapies. Seven percent had a prior ASCT.

T-cell NHL patients were 55% male, 73% had an ECOG status of 1, and they had a median of 4 (range, 1 to 11) prior systemic therapies. None had a prior ASCT.

MM patients were 86% male, 71% had an ECOG status of 1, and they had a median of 5 (range, 2 to 20) prior systemic therapies. More than half had a prior ASCT.

Patient disposition

With follow-up approaching a year, more patients with HL are still on treatment (39%) compared with B-cell NHL (13%), T-cell NHL (18%), and MM (0%) patients.

“Of note, however, is that the reasons for going off treatment were predominantly disease progression,” Dr Ansell said.

“The vast majority of patients who came off treatment came off treatment because their disease progressed, and the numbers that came off because of toxicity were relatively low.”

Seven HL patients went off treatment due to disease progression and 2 due to study drug toxicity.

Eleven B-cell NHL patients went off treatment due to disease progression and 2 withdrew due to unrelated adverse events (AEs).

Five T-cell NHL patients went off treatment due to disease progression and 2 due to study drug toxicity.

And 4 MM patients withdrew due to disease progression, 1 due to study drug toxicity, and 1 due to AEs unrelated to the study drug.

About two-thirds of HL patients, over 90% of B-cell NHL patients, about 80% of T-cell NHL patients, and about 70% of MM patients received 90% or more of the intended dose of each drug.

Safety

One patient with primary mediastinal B-cell lymphoma was included in the safety analysis, for a total of 65 patients treated.

“The majority of patients had some degree of adverse event,” Dr Ansell explained. “But if one looks at the grade 3 and 4 adverse events, those were seen in a more modest number of patients, in a minority of patients. And most importantly, if one looks at the adverse events that led to discontinuation, one can see that this was in a significant minority of patients.”

Five patients discontinued due to treatment-related AEs, which were pneumonitis (n=3), pneumonia and pneumonitis (n=1), and diabetic ketoacidosis (n=1).

Overall, 51 patients (78%) experienced an AE; 19 (29%) had a grade 3–4 AE, 14 (22%) had a serious AE, and 5 (8%) discontinued due to an AE.

Of 31 HL patients, 28 (90%) had an AE, 8 (26%) had a grade 3–4 AE, 6 (19%) had a serious AE, and 2 (6%) discontinued due to an AE.

All 11 T-cell NHL patients experienced an AE, 5 patients (45%) a grade 3-4 AE, 4 patients (36%) had a serious AE, and 2 patients (18%) discontinued because of an AE.

About half of B-cell NHL and MM patients experienced an AE, with 1 MM patient discontinuing as a result of it and no B-cell NHL patient discontinuing due to an AE.

“I would highlight that most of the adverse events were, as expected, immunological in nature . . . . ,” Dr Ansell said. “A very modest number of patients had grade 3 and 4 toxicities.”

The most common drug-related AEs of any grade were fatigue (n=17; 26%), pyrexia (n=15; 23%), rash (n=7; 11%), diarrhea (n=12; 18%), and nausea, pneumonitis, cough, and infusion-related reactions, with 9 patients each (14%).

Efficacy

Twenty-three HL patients (74%) achieved an overall response, including 6 patients (19%) with a complete response and 17 (55%) with a partial response. Three patients (10%) had stable disease, and 3 (10%) had relapsed or progressive disease. Response was not reported for 2 patients (6%).

“Most of these responses are durable, and, very encouraging, you can see patients out approaching a year continuing on therapy,” Dr Ansell said.

The ORR in the 18 transplant-naive patients was 67% (n=67).

The median duration of response for HL patients was not reached and ranged from 0.0 to 13.4 months.

B-cell NHL patients had an ORR of 20% (n=3). There were no complete responses and 3 (20%) partial responses. One patient (7%) had stable disease, and 8 (53%) had relapsed or progressive disase. The median duration of partial response was not reached and ranged from 11.0 to 12.7 months.

T-cell NHL patients had an ORR of 9% (n=1). There were no complete responses and 1 (9%) partial response. Four patients (36%) had stable disease, and 3 (27%) had relapsed or progressive disease. The median duration of partial response was not reached and was 3.9 months.

Except for 1 patient with stable disease, MM patients did not respond to therapy.

Biomarker analysis

All 19 HL patients with a known PD-L1 status at baseline saw their tumor burden decrease to below baseline levels. This may be because HL is characterized by high PD-L1 expression and high responsiveness to checkpoint blockade.

Patients with NHL, on the other hand, have a diverse group of tumors characterized by variable PD-L1 expression. Eight of 13 patients with known expression saw their tumor burden decrease with treatment to below baseline.

Encouraged by the results, the investigators believe further investigation of the combination is in order, as the combination, with limited follow-up, achieved a high and durable ORR in HL patients, including those who were transplant-naïve.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Andreas Engert, MD

In this editorial, Andreas Engert, MD, makes the case for consolidation therapy in advanced Hodgkin lymphoma.

Dr Engert is a professor of internal medicine, hematology, and oncology at University Hospital of Cologne in Germany. He has received research funding and consultancy fees from Takeda/Millennium Pharmaceuticals and Affimed as well as research funding from Bristol-Myers Squibb.

Historically, Hodgkin lymphoma has been viewed as a cancer with generally favorable outcomes. However, it’s clear that there is an unmet need for patients with advanced stage disease.

Physicians treat newly diagnosed patients with a curative intent, but up to 30% fail to respond to initial therapy or relapse, depending on the treatment regimen used, stage of disease, and risk factors.^1-3 Additionally, toxicity from frontline treatment has the potential to impact patients throughout their lives.

In line with the current standard of care, the majority of patients who fail frontline therapy will receive high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

This path of treatment, similar to frontline regimens, can be effective in eradicating the disease, but approximately half of those who undergo an ASCT subsequently relapse. Outcomes are generally poor for patients whose disease returns post-ASCT, especially if the relapse occurs within the first year.⁴

Consolidation therapy, used to kill remaining cancer cells after ASCT, may offer a new treatment option to address this problem. Unlike longer-term maintenance therapy, consolidation typically lasts for a short period of time—normally months instead of years—and involves intense treatment to eradicate any remaining disease.

The evidence for consolidation therapy in Hodgkin lymphoma

To understand the rationale for consolidation therapy, first consider why some patients with Hodgkin lymphoma relapse following ASCT. A small number of cancer cells, undetectable using traditional diagnostics, may remain following ASCT. This is known as minimal residual disease, and it may indicate the potential for the cancer to return.

The goal of consolidation therapy is to eliminate minimal residual disease before it progresses and causes a relapse. Unsurprisingly, timing plays a crucial role in the likelihood of achieving that goal.

In order to allow for the best chance for optimal patient outcomes, consolidation treatment should be initiated shortly after ASCT, before regrowth of cancer cells can occur. Tolerability is paramount, though, and timing must be carefully weighed by the treating physician.

Physicians and researchers learned about the impact and use of consolidation therapy from its success in other blood cancers like chronic myeloid leukemia.^5,6

To prove the concept of consolidation treatment in Hodgkin lymphoma, a controlled clinical trial was conducted. The AETHERA study evaluated the use of brentuximab vedotin as consolidation therapy in patients with advanced Hodgkin lymphoma who were at increased risk of relapse or progression following ASCT.⁷

AETHERA was the first completed phase 3 study to explore consolidation treatment immediately following ASCT as a way of extending the effect of transplant in patients with Hodgkin lymphoma.

The results made a strong argument in favor of consolidation therapy, as patients who received brentuximab vedotin plus best supportive care after ASCT lived significantly longer without their disease worsening versus those on the placebo regimen. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.

Based on these data, consolidation therapy with brentuximab vedotin has been approved in several countries as a treatment option for patients with Hodgkin lymphoma who are at increased risk for relapse or progression following ASCT.

An important next step: Treating the right patients at the right time

Translating clinical evidence into real-world practice, physicians must look at which patients are most likely to benefit from consolidation therapy following ASCT—namely, those who are at increased risk of relapse. The effort to identify clear risk factors for relapse is still in progress.

Researchers across the world are currently studying patient characteristics and outcomes to determine a definitive set of risk factors that can better illustrate which patients should receive consolidation treatment.

Examples of factors under consideration include the stage of disease at diagnosis, tumor size, time to relapse, and response to previous treatment.⁸ Experts generally agree, however, that increased risk is cumulative and that it is not clear that any one risk factor is more important than others.

As researchers work to answer outstanding questions about consolidation therapy, there are a number of actions that the Hodgkin lymphoma community can take to help bring the right treatment options to patients.

Existing guidelines need to be evaluated and, if appropriate, adapted to give physicians across the globe the information that will allow them to provide the best care for patients at increased risk of relapse following ASCT.

Hematologists and oncologists then have the responsibility to stay informed of revisions to guidelines and to practically apply the latest research of consolidation therapy into their clinical practices.

The possibility now exists to potentially cure some Hodgkin lymphoma patients within a group that has traditionally experienced poor outcomes. As a result, a new treatment paradigm in this setting is emerging—one that may help solve the challenge of post-ASCT relapse in Hodgkin lymphoma.

Additional information on the use of consolidation therapy in Hodgkin lymphoma is available in the paper, Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat?

¹ Diehl, V, Franklin, J, Pfreundschuh, M, et al. Standard and Increased-Dose BEACOPP Chemotherapy Compared with COPP-ABVD for Advanced Hodgkin’s Disease. N Engl J Med 2003;348:2386-95.

² Duggan, D, Petroni, G, Johnson, J, et al. Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial. J Clin Oncol 2003;21:607-614.

3 Federico, M, Luminari, S, Iannitto, E, et al. ABVD Compared With BEACOPP Compared With CEC for the Initial Treatment of Patients With Advanced Hodgkin’s Lymphoma: Results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805-811.

4 Arai S, Fanale M, deVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.

5 Zonder, J and Schiffer, C. Update on practical aspects of the treatment of chronic myeloid leukemia with imatinib mesylate. Curr Hematol Malig Rep 2006;1:141.

6 Giralt SA, Arora M, Goldman JM, et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007;137(5):461-467.

7 Moskowitz CH, Nadamanee A, Masszi T, et al; for the AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.

8 Bröckelmann PJ, Müller H, Casasnovas O, et al. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (rrHL). Poster presented at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers have estimated the global incidence of 32 cancer types and deaths related to these malignancies in 2015.

The group’s data, published in JAMA Oncology, suggest there were 17.5 million cancer cases and 8.7 million cancer deaths last year.

There were 78,000 cases of Hodgkin lymphoma and 24,000 deaths from the disease, as well as 666,000 cases of non-Hodgkin lymphoma (NHL) and 231,000 NHL deaths.

There were 154,000 cases of multiple myeloma and 101,000 deaths from the disease.

And there were 606,000 cases of leukemia, with 353,000 leukemia deaths. This included 161,000 cases of acute lymphoid leukemia (110,000 deaths), 191,000 cases of chronic lymphoid leukemia (61,000 deaths), 190,000 cases of acute myeloid leukemia (147,000 deaths), and 64,000 cases of chronic myeloid leukemia (35,000 deaths).

The data also show that, between 2005 and 2015, cancer cases increased by 33%, mostly due to population aging and growth, plus changes in age-specific cancer rates.

Globally, the odds of developing cancer during a lifetime were 1 in 3 for men and 1 in 4 for women in 2015.

Prostate cancer was the most common cancer in men (1.6 million cases), although tracheal, bronchus, and lung cancer was the leading cause of cancer deaths for men.

Breast cancer was the most common cancer for women (2.4 million cases) and the leading cause of cancer deaths in women.

The most common childhood cancers were leukemia, “other neoplasms,” NHL, and brain and nervous system cancers.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers have estimated the global incidence of 32 cancer types and deaths related to these malignancies in 2015.

The group’s data, published in JAMA Oncology, suggest there were 17.5 million cancer cases and 8.7 million cancer deaths last year.

There were 78,000 cases of Hodgkin lymphoma and 24,000 deaths from the disease, as well as 666,000 cases of non-Hodgkin lymphoma (NHL) and 231,000 NHL deaths.

There were 154,000 cases of multiple myeloma and 101,000 deaths from the disease.

And there were 606,000 cases of leukemia, with 353,000 leukemia deaths. This included 161,000 cases of acute lymphoid leukemia (110,000 deaths), 191,000 cases of chronic lymphoid leukemia (61,000 deaths), 190,000 cases of acute myeloid leukemia (147,000 deaths), and 64,000 cases of chronic myeloid leukemia (35,000 deaths).

The data also show that, between 2005 and 2015, cancer cases increased by 33%, mostly due to population aging and growth, plus changes in age-specific cancer rates.

Globally, the odds of developing cancer during a lifetime were 1 in 3 for men and 1 in 4 for women in 2015.

Prostate cancer was the most common cancer in men (1.6 million cases), although tracheal, bronchus, and lung cancer was the leading cause of cancer deaths for men.

Breast cancer was the most common cancer for women (2.4 million cases) and the leading cause of cancer deaths in women.

The most common childhood cancers were leukemia, “other neoplasms,” NHL, and brain and nervous system cancers.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers have estimated the global incidence of 32 cancer types and deaths related to these malignancies in 2015.

The group’s data, published in JAMA Oncology, suggest there were 17.5 million cancer cases and 8.7 million cancer deaths last year.

There were 78,000 cases of Hodgkin lymphoma and 24,000 deaths from the disease, as well as 666,000 cases of non-Hodgkin lymphoma (NHL) and 231,000 NHL deaths.

There were 154,000 cases of multiple myeloma and 101,000 deaths from the disease.

And there were 606,000 cases of leukemia, with 353,000 leukemia deaths. This included 161,000 cases of acute lymphoid leukemia (110,000 deaths), 191,000 cases of chronic lymphoid leukemia (61,000 deaths), 190,000 cases of acute myeloid leukemia (147,000 deaths), and 64,000 cases of chronic myeloid leukemia (35,000 deaths).

The data also show that, between 2005 and 2015, cancer cases increased by 33%, mostly due to population aging and growth, plus changes in age-specific cancer rates.

Globally, the odds of developing cancer during a lifetime were 1 in 3 for men and 1 in 4 for women in 2015.

Prostate cancer was the most common cancer in men (1.6 million cases), although tracheal, bronchus, and lung cancer was the leading cause of cancer deaths for men.

Breast cancer was the most common cancer for women (2.4 million cases) and the leading cause of cancer deaths in women.

The most common childhood cancers were leukemia, “other neoplasms,” NHL, and brain and nervous system cancers.

Pembrolizumab (Keytruda)

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted priority review to the supplemental biologics license application (sBLA) for pembrolizumab (Keytruda®) as a treatment for patients with refractory classical Hodgkin lymphoma (cHL) and for cHL patients who have relapsed after 3 or more prior lines of therapy.

The sBLA will be reviewed under the FDA’s accelerated approval program. The target action date is March 15, 2017.

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, already has FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Pembrolizumab also has breakthrough therapy designation as a treatment for relapsed/refractory cHL.

The current sBLA for pembrolizumab is seeking approval for the drug at a fixed dose of 200 mg, administered intravenously every 3 weeks.

This is the first application for regulatory approval of pembrolizumab in a hematologic malignancy.

The sBLA is supported by data from the phase 1 KEYNOTE-013 trial and the phase 2 KEYNOTE-087 trial.

Results from KEYNOTE-013 (in cHL patients) were presented at the 2014 ASH Annual Meeting, and results from KEYNOTE-087 were presented at the 2016 ASCO Annual Meeting.

Pembrolizumab (Keytruda)

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted priority review to the supplemental biologics license application (sBLA) for pembrolizumab (Keytruda®) as a treatment for patients with refractory classical Hodgkin lymphoma (cHL) and for cHL patients who have relapsed after 3 or more prior lines of therapy.

The sBLA will be reviewed under the FDA’s accelerated approval program. The target action date is March 15, 2017.

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, already has FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Pembrolizumab also has breakthrough therapy designation as a treatment for relapsed/refractory cHL.

The current sBLA for pembrolizumab is seeking approval for the drug at a fixed dose of 200 mg, administered intravenously every 3 weeks.

This is the first application for regulatory approval of pembrolizumab in a hematologic malignancy.

The sBLA is supported by data from the phase 1 KEYNOTE-013 trial and the phase 2 KEYNOTE-087 trial.

Results from KEYNOTE-013 (in cHL patients) were presented at the 2014 ASH Annual Meeting, and results from KEYNOTE-087 were presented at the 2016 ASCO Annual Meeting.

Pembrolizumab (Keytruda)

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted priority review to the supplemental biologics license application (sBLA) for pembrolizumab (Keytruda®) as a treatment for patients with refractory classical Hodgkin lymphoma (cHL) and for cHL patients who have relapsed after 3 or more prior lines of therapy.

The sBLA will be reviewed under the FDA’s accelerated approval program. The target action date is March 15, 2017.

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, already has FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Pembrolizumab also has breakthrough therapy designation as a treatment for relapsed/refractory cHL.

The current sBLA for pembrolizumab is seeking approval for the drug at a fixed dose of 200 mg, administered intravenously every 3 weeks.

This is the first application for regulatory approval of pembrolizumab in a hematologic malignancy.

The sBLA is supported by data from the phase 1 KEYNOTE-013 trial and the phase 2 KEYNOTE-087 trial.

Results from KEYNOTE-013 (in cHL patients) were presented at the 2014 ASH Annual Meeting, and results from KEYNOTE-087 were presented at the 2016 ASCO Annual Meeting.

Nivolumab (Opdivo)

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The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

Nivolumab (Opdivo)

Photo from Business Wire

The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

Nivolumab (Opdivo)

Photo from Business Wire

The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

Nivolumab (Opdivo)

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COLOGNE—Results from the CheckMate -205 study suggest nivolumab can produce a high objective response rate (ORR) in patients with heavily pretreated classical Hodgkin lymphoma (cHL).

Investigators recently presented results from one of the cohorts in this phase 2 trial—cohort C—which included cHL patients who received nivolumab after undergoing autologous hematopoietic stem cell transplant (auto-HSCT) and receiving treatment with brentuximab vedotin (BV).

At a median follow-up of 8.8 months, the ORR, as assessed by an independent radiologic review committee (IRRC), was 73%.

The median progression-free survival (PFS) was 11.2 months, and the 6-month overall survival (OS) was 94%.

Investigators said the safety profile of nivolumab in this patient population was consistent with previously reported data in patients with cHL, and no new clinically meaningful safety signals were identified.

“These data from cohort C build on existing evidence supporting the benefit of Opdivo [nivolumab] in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said investigator Andreas Engert, MD, of the University Hospital of Cologne in Germany.

“Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients.”

The results were presented at the 10th International Symposium on Hodgkin Lymphoma (abstract T022). Abstracts from this meeting have been published in haematologica.

The CheckMate -205 trial is sponsored by Bristol-Myers Squibb.

About the trial

CheckMate -205 is a multi-cohort study in which investigators are evaluating the safety and efficacy of nivolumab in adults with cHL.

Cohort A included cHL patients who had received auto-HSCT and were BV-naïve (n=63). Cohort B included cHL patients who had received auto-HSCT followed by BV (n=80).

Cohort C included cHL patients who had received BV before and/or after auto-HSCT (n=100).

The study also includes a cohort D, which is currently enrolling and evaluating nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Patients enrolled in this trial have received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. In cohort C, patients were also treated until investigator-assessed complete response (CR) lasting 1 year.

The study’s primary endpoint was ORR by IRRC assessment. Secondary and other exploratory endpoints included duration of response by IRRC assessment for CR rate and partial response rate, PFS by IRRC assessment, OS, and safety.

Response

The investigators presented results from cohort C (n=100), which included patients with cHL who had received BV before and/or after auto-HSCT.

At a median follow-up of 8.8 months, ORR per the IRRC was 73% (n=73) overall. The investigators said ORR was consistent across patient subgroups, regardless of the timing of prior BV relative to auto-HSCT.

The ORR was 70% (n=23) in patients who received BV only before auto-HSCT, 72% (n=41) in patients who received BV only after auto-HSCT, and 88% (n=7) in patients who received BV before and after auto-HSCT.

The CR rate was 17% (n=17) overall, 18.2% (n=6) in patients who received BV only before auto-HSCT, 12.3% (n=7) in patients who received BV only after auto-HSCT, and 38% (n=3) in patients who received BV before and after auto-HSCT.

Survival

The median PFS was 11.2 months (range, 8.5 months to not achieved) overall, 11.2 months (range, 8.5 months to not achieved) in patients who received BV only before auto-HSCT, 8.9 months (range, 8.3 months to not achieved) in patients who received BV only after auto-HSCT, and not achieved (range, 5.6 months to not achieved) in patients who received BV before and after auto-HSCT.

The 6-month OS was 93.9% overall, 97% in patients who received BV only before auto-HSCT, 91% in patients who received BV only after auto-HSCT, and 100% in patients who received BV before and after auto-HSCT.

Safety

Treatment-related adverse events (AEs) occurred in 68% of patients between the first dose and 30 days after the last dose of nivolumab. The most common treatment-related AEs were diarrhea, infusion-related reaction, and fatigue (11% each).

Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients.

At present, no treatment-related deaths have been reported.

Nivolumab (Opdivo)

Photo from Business Wire

COLOGNE—Results from the CheckMate -205 study suggest nivolumab can produce a high objective response rate (ORR) in patients with heavily pretreated classical Hodgkin lymphoma (cHL).

Investigators recently presented results from one of the cohorts in this phase 2 trial—cohort C—which included cHL patients who received nivolumab after undergoing autologous hematopoietic stem cell transplant (auto-HSCT) and receiving treatment with brentuximab vedotin (BV).

At a median follow-up of 8.8 months, the ORR, as assessed by an independent radiologic review committee (IRRC), was 73%.

The median progression-free survival (PFS) was 11.2 months, and the 6-month overall survival (OS) was 94%.

Investigators said the safety profile of nivolumab in this patient population was consistent with previously reported data in patients with cHL, and no new clinically meaningful safety signals were identified.

“These data from cohort C build on existing evidence supporting the benefit of Opdivo [nivolumab] in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said investigator Andreas Engert, MD, of the University Hospital of Cologne in Germany.

“Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients.”

The results were presented at the 10th International Symposium on Hodgkin Lymphoma (abstract T022). Abstracts from this meeting have been published in haematologica.

The CheckMate -205 trial is sponsored by Bristol-Myers Squibb.

About the trial

CheckMate -205 is a multi-cohort study in which investigators are evaluating the safety and efficacy of nivolumab in adults with cHL.

Cohort A included cHL patients who had received auto-HSCT and were BV-naïve (n=63). Cohort B included cHL patients who had received auto-HSCT followed by BV (n=80).

Cohort C included cHL patients who had received BV before and/or after auto-HSCT (n=100).

The study also includes a cohort D, which is currently enrolling and evaluating nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Patients enrolled in this trial have received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. In cohort C, patients were also treated until investigator-assessed complete response (CR) lasting 1 year.

The study’s primary endpoint was ORR by IRRC assessment. Secondary and other exploratory endpoints included duration of response by IRRC assessment for CR rate and partial response rate, PFS by IRRC assessment, OS, and safety.

Response

The investigators presented results from cohort C (n=100), which included patients with cHL who had received BV before and/or after auto-HSCT.

At a median follow-up of 8.8 months, ORR per the IRRC was 73% (n=73) overall. The investigators said ORR was consistent across patient subgroups, regardless of the timing of prior BV relative to auto-HSCT.

The ORR was 70% (n=23) in patients who received BV only before auto-HSCT, 72% (n=41) in patients who received BV only after auto-HSCT, and 88% (n=7) in patients who received BV before and after auto-HSCT.

The CR rate was 17% (n=17) overall, 18.2% (n=6) in patients who received BV only before auto-HSCT, 12.3% (n=7) in patients who received BV only after auto-HSCT, and 38% (n=3) in patients who received BV before and after auto-HSCT.

Survival

The median PFS was 11.2 months (range, 8.5 months to not achieved) overall, 11.2 months (range, 8.5 months to not achieved) in patients who received BV only before auto-HSCT, 8.9 months (range, 8.3 months to not achieved) in patients who received BV only after auto-HSCT, and not achieved (range, 5.6 months to not achieved) in patients who received BV before and after auto-HSCT.

The 6-month OS was 93.9% overall, 97% in patients who received BV only before auto-HSCT, 91% in patients who received BV only after auto-HSCT, and 100% in patients who received BV before and after auto-HSCT.

Safety

Treatment-related adverse events (AEs) occurred in 68% of patients between the first dose and 30 days after the last dose of nivolumab. The most common treatment-related AEs were diarrhea, infusion-related reaction, and fatigue (11% each).

Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients.

At present, no treatment-related deaths have been reported.

Nivolumab (Opdivo)

Photo from Business Wire

COLOGNE—Results from the CheckMate -205 study suggest nivolumab can produce a high objective response rate (ORR) in patients with heavily pretreated classical Hodgkin lymphoma (cHL).

Investigators recently presented results from one of the cohorts in this phase 2 trial—cohort C—which included cHL patients who received nivolumab after undergoing autologous hematopoietic stem cell transplant (auto-HSCT) and receiving treatment with brentuximab vedotin (BV).

At a median follow-up of 8.8 months, the ORR, as assessed by an independent radiologic review committee (IRRC), was 73%.

The median progression-free survival (PFS) was 11.2 months, and the 6-month overall survival (OS) was 94%.

Investigators said the safety profile of nivolumab in this patient population was consistent with previously reported data in patients with cHL, and no new clinically meaningful safety signals were identified.

“These data from cohort C build on existing evidence supporting the benefit of Opdivo [nivolumab] in classical Hodgkin lymphoma patients who have relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin,” said investigator Andreas Engert, MD, of the University Hospital of Cologne in Germany.

“Results from cohort C indicated a benefit with Opdivo regardless of the order of prior treatment with autologous hematopoietic stem cell transplantation and brentuximab vedotin, providing important insights as we continue researching the potential role Opdivo could provide for heavily pretreated classical Hodgkin lymphoma patients.”

The results were presented at the 10th International Symposium on Hodgkin Lymphoma (abstract T022). Abstracts from this meeting have been published in haematologica.

The CheckMate -205 trial is sponsored by Bristol-Myers Squibb.

About the trial

CheckMate -205 is a multi-cohort study in which investigators are evaluating the safety and efficacy of nivolumab in adults with cHL.

Cohort A included cHL patients who had received auto-HSCT and were BV-naïve (n=63). Cohort B included cHL patients who had received auto-HSCT followed by BV (n=80).

Cohort C included cHL patients who had received BV before and/or after auto-HSCT (n=100).

The study also includes a cohort D, which is currently enrolling and evaluating nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Patients enrolled in this trial have received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. In cohort C, patients were also treated until investigator-assessed complete response (CR) lasting 1 year.

The study’s primary endpoint was ORR by IRRC assessment. Secondary and other exploratory endpoints included duration of response by IRRC assessment for CR rate and partial response rate, PFS by IRRC assessment, OS, and safety.

Response

The investigators presented results from cohort C (n=100), which included patients with cHL who had received BV before and/or after auto-HSCT.

At a median follow-up of 8.8 months, ORR per the IRRC was 73% (n=73) overall. The investigators said ORR was consistent across patient subgroups, regardless of the timing of prior BV relative to auto-HSCT.

The ORR was 70% (n=23) in patients who received BV only before auto-HSCT, 72% (n=41) in patients who received BV only after auto-HSCT, and 88% (n=7) in patients who received BV before and after auto-HSCT.

The CR rate was 17% (n=17) overall, 18.2% (n=6) in patients who received BV only before auto-HSCT, 12.3% (n=7) in patients who received BV only after auto-HSCT, and 38% (n=3) in patients who received BV before and after auto-HSCT.

Survival

The median PFS was 11.2 months (range, 8.5 months to not achieved) overall, 11.2 months (range, 8.5 months to not achieved) in patients who received BV only before auto-HSCT, 8.9 months (range, 8.3 months to not achieved) in patients who received BV only after auto-HSCT, and not achieved (range, 5.6 months to not achieved) in patients who received BV before and after auto-HSCT.

The 6-month OS was 93.9% overall, 97% in patients who received BV only before auto-HSCT, 91% in patients who received BV only after auto-HSCT, and 100% in patients who received BV before and after auto-HSCT.

Safety

Treatment-related adverse events (AEs) occurred in 68% of patients between the first dose and 30 days after the last dose of nivolumab. The most common treatment-related AEs were diarrhea, infusion-related reaction, and fatigue (11% each).

Grade 3/4 AEs occurred in 19% of patients. Serious treatment-related AEs were reported in 17% of patients, and treatment-related AEs leading to discontinuation occurred in 6% of patients.

At present, no treatment-related deaths have been reported.

Cancer patient receives therapy

Photo by Rhoda Baer

A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.

The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.

For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.

Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.

The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.

The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.

DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.

Top 10 contributors

The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).

The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).

The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.

They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).

The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).

DALYs by race/ethnicity

The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.

Age-standardized DALYs lost (per 100,000 individuals) were as follows:

All cancers combined

3588 for non-Hispanic blacks

2898 for non-Hispanic whites

1978 for Hispanics

1798 for non-Hispanic Asians.

Leukemia

115 for non-Hispanic blacks and non-Hispanic whites

98 for Hispanics

82 for non-Hispanic Asians.

NHL

93 for non-Hispanic whites

86 for non-Hispanic blacks

78 for Hispanics

60 for non-Hispanic Asians.

Hodgkin lymphoma

11 for non-Hispanic blacks

10 for non-Hispanic whites and Hispanics

3 for non-Hispanic Asians.

Myeloma

93 for non-Hispanic blacks

43 for non-Hispanic whites

42 for Hispanics

26 for non-Hispanic Asians.

The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.

Cancer patient receives therapy

Photo by Rhoda Baer

A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.

The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.

For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.

Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.

The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.

The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.

DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.

Top 10 contributors

The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).

The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).

The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.

They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).

The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).

DALYs by race/ethnicity

The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.

Age-standardized DALYs lost (per 100,000 individuals) were as follows:

All cancers combined

3588 for non-Hispanic blacks

2898 for non-Hispanic whites

1978 for Hispanics

1798 for non-Hispanic Asians.

Leukemia

115 for non-Hispanic blacks and non-Hispanic whites

98 for Hispanics

82 for non-Hispanic Asians.

NHL

93 for non-Hispanic whites

86 for non-Hispanic blacks

78 for Hispanics

60 for non-Hispanic Asians.

Hodgkin lymphoma

11 for non-Hispanic blacks

10 for non-Hispanic whites and Hispanics

3 for non-Hispanic Asians.

Myeloma

93 for non-Hispanic blacks

43 for non-Hispanic whites

42 for Hispanics

26 for non-Hispanic Asians.

The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.

Cancer patient receives therapy

Photo by Rhoda Baer

A new study suggests that leukemia and non-Hodgkin lymphoma (NHL) are among the top 10 cancers with the greatest burden (most years of healthy life lost) in the US.

The research also showed that the burden of different cancer types varied between patients belonging to different racial/ethnic groups.

For example, the contribution of leukemia to the overall cancer burden was twice as high in Hispanics as it was in non-Hispanic blacks. The same was true for NHL.

Joannie Lortet-Tieulent, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in the American Journal of Preventive Medicine.

The researchers calculated the burden of cancer in the US in 2011 for 24 cancer types. They calculated burden using disability-adjusted life years (DALYs), which combine cancer incidence, mortality, survival, and quality of life into a summary indicator.

The results suggested the burden of cancer in 2011 was over 9.8 million DALYs, which was equally shared between men and women—4.9 million DALYs for each sex.

DALYs lost to cancer were mostly related to premature death due to cancer (91%). The remaining 9% were related to impaired quality of life because of the disease or its treatment, or other disease-related issues.

Top 10 contributors

The researchers calculated the proportion of DALYs lost for each of the cancer types. And they found that lung cancer was the largest contributor to the loss of healthy years, accounting for 24% of the burden (2.4 million DALYs).

The second biggest contributor to the loss of healthy years was breast cancer (10%), followed by colorectal cancer (9%), pancreatic cancer (6%), prostate cancer (5%), leukemia (4%), liver cancer (4%), brain cancer (3%), NHL (3%), and ovarian cancer (3%).

The researchers also calculated the proportion of DALYs lost from the top 10 cancer types according to race/ethnicity.

They found the contribution of leukemia to the loss of healthy years was greatest for Hispanics (6%), followed by non-Hispanic Asians (5%), non-Hispanic whites (4%), and non-Hispanic blacks (3%).

The contribution of NHL to the loss of healthy years was greatest for Hispanics (4%), followed by non-Hispanic Asians/non-Hispanic whites (3% for both), and non-Hispanic blacks (2%).

DALYs by race/ethnicity

The researchers found that, overall, the cancer burden was highest in non-Hispanic blacks, followed by non-Hispanic whites, Hispanics, and non-Hispanic Asians. However, this pattern was not consistent across the different cancer types.

Age-standardized DALYs lost (per 100,000 individuals) were as follows:

All cancers combined

3588 for non-Hispanic blacks

2898 for non-Hispanic whites

1978 for Hispanics

1798 for non-Hispanic Asians.

Leukemia

115 for non-Hispanic blacks and non-Hispanic whites

98 for Hispanics

82 for non-Hispanic Asians.

NHL

93 for non-Hispanic whites

86 for non-Hispanic blacks

78 for Hispanics

60 for non-Hispanic Asians.

Hodgkin lymphoma

11 for non-Hispanic blacks

10 for non-Hispanic whites and Hispanics

3 for non-Hispanic Asians.

Myeloma

93 for non-Hispanic blacks

43 for non-Hispanic whites

42 for Hispanics

26 for non-Hispanic Asians.

The researchers noted that, despite these differences, the cancer burden in all races/ethnicities was driven by years of life lost. They said this highlights the need to prevent deaths by improving prevention, early detection, and treatment of cancers.

HIV-infected individuals on antiretroviral therapy who also have chronic coinfection with hepatitis B or C virus have an increased risk of developing non-Hodgkin lymphoma, according to new research published in Annals of Internal Medicine.

Lead author Qing Wang, PhD, of the Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel, Switzerland, and her coauthors said there is growing evidence of an association between both chronic hepatitis B virus infection (HBV) and chronic hepatitis C virus infection (HCV), and non-Hodgkin lymphoma, with chronic immune activation and B cell proliferation suggested as potential mechanisms. However, the impact of chronic coinfection in individuals with HIV is unclear.

©vchal/Thinkstock

HIV-infected individuals on antiretroviral therapy who also have chronic coinfection with hepatitis B or C virus have an increased risk of developing non-Hodgkin lymphoma, according to new research published in Annals of Internal Medicine.

Lead author Qing Wang, PhD, of the Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel, Switzerland, and her coauthors said there is growing evidence of an association between both chronic hepatitis B virus infection (HBV) and chronic hepatitis C virus infection (HCV), and non-Hodgkin lymphoma, with chronic immune activation and B cell proliferation suggested as potential mechanisms. However, the impact of chronic coinfection in individuals with HIV is unclear.

©vchal/Thinkstock

HIV-infected individuals on antiretroviral therapy who also have chronic coinfection with hepatitis B or C virus have an increased risk of developing non-Hodgkin lymphoma, according to new research published in Annals of Internal Medicine.

Lead author Qing Wang, PhD, of the Basel Institute for Clinical Epidemiology & Biostatistics at University Hospital Basel, Switzerland, and her coauthors said there is growing evidence of an association between both chronic hepatitis B virus infection (HBV) and chronic hepatitis C virus infection (HCV), and non-Hodgkin lymphoma, with chronic immune activation and B cell proliferation suggested as potential mechanisms. However, the impact of chronic coinfection in individuals with HIV is unclear.

©vchal/Thinkstock

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”

 

 

Cancer patient receives therapy

Photo by Rhoda Baer

 

A new report highlights recent advances made in the fight against cancer but suggests the burden of cancer in the US is still on the rise.

The AACR Cancer Progress Report 2016 states that the number of cancer survivors in the US rose by 1 million from 2014 to 2016, reaching an estimated 15.5 million.

Meanwhile, the US Food and Drug Administration (FDA) approved new treatments for a range of cancers.

Between August 1, 2015, and July 31, 2016, the FDA approved 13 new anticancer therapies and new uses for 11 previously approved anticancer therapies.

Six of these drugs were approved to treat hematologic malignancies:

• Venetoclax for chronic lymphocytic leukemia
• Daratumumab for multiple myeloma
• Elotuzumab for multiple myeloma
• Ixazomib for multiple myeloma
• Obinutuzumab for follicular lymphoma
• Nivolumab for classical Hodgkin lymphoma.

The report notes that the use of immunotherapy, in particular, is on the rise. For example, on August 1, 2015, checkpoint inhibitors were approved for just 2 cancers—melanoma and lung cancer.

As of September 1, 2016, checkpoint inhibitors have been approved for 6 cancers—Hodgkin lymphoma, bladder cancer, head and neck cancer, kidney cancer, lung cancer, and melanoma.

“The promise of immunotherapy for cancer therapy has never been greater, and the opportunity to make significant progress in this critical area is real,” said Nancy E. Davidson, MD, president of the AACR and director of the University of Pittsburgh Cancer Institute in Pennsylvania.

“However, continued progress is going to require a sustained federal commitment to the research agenda. And in fact, if the necessary funding is provided, we will accelerate the pace of progress and, in turn, markedly reduce morbidity and mortality from cancer.”

Growing burden of cancer

The report emphasizes that although advances are being made against cancers, these diseases continue to exert an immense personal and economic toll, and the burden of cancer is expected to grow in the coming decades.

According to the report:

• More than 595,000 people in the US are projected to die from cancer in 2016
• Cancer is the number one cause of disease-related death among US children
• The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035
• It is estimated that the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs will rise to $156 billion in 2020.

The report states that the increasing economic and personal burden of cancer underscores the need for more research to develop new approaches to cancer prevention and treatment.

The report also highlights the recommendations of the National Cancer Moonshot Initiative Blue Ribbon Panel for accelerating the pace of progress in cancer research.

“Research has made tremendous advances against cancer,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, we need to accelerate the pace of progress because it is unacceptable that 1 American will die of cancer every minute of every day this year.”