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Single-dose NEPA found non-inferior to aprepitant/granisetron
WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).
The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.
They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.
Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).
NEPA is a combination of the selective NK1RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3RA, palonosetron (0.5 mg) for the prevention of CINV.
Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.
Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.
It is formulated into a single oral capsule.
Study design
The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.
Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).
All patients received oral dexamethasone on days 1-4.
The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.
The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at ̶ 10%.
Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).
Results
The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.
The most common cancer types were lung and head and neck cancer.
Patients had received a median cisplatin dose of 73 and 72 mg/m2 in the NEPA and APR/GRAN arms, respectively.
Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).
In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).
Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).
Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.
However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.
Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.
Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.
The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.
Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.
The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.
NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.
For the full US prescribing information, see the package insert.
WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).
The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.
They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.
Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).
NEPA is a combination of the selective NK1RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3RA, palonosetron (0.5 mg) for the prevention of CINV.
Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.
Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.
It is formulated into a single oral capsule.
Study design
The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.
Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).
All patients received oral dexamethasone on days 1-4.
The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.
The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at ̶ 10%.
Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).
Results
The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.
The most common cancer types were lung and head and neck cancer.
Patients had received a median cisplatin dose of 73 and 72 mg/m2 in the NEPA and APR/GRAN arms, respectively.
Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).
In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).
Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).
Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.
However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.
Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.
Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.
The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.
Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.
The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.
NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.
For the full US prescribing information, see the package insert.
WASHINGTON, DC—In a head-to-head study comparing a single-dose oral antiemetic to a 3-day oral regimen, the single dose has shown itself to be non-inferior to the multi-day regimen in preventing chemotherapy-induced nausea and vomiting (CINV).
The investigators evaluated netupitant/palonosetron (NEPA) against aprepitant/granisetron (APR/GRAN) in patients on highly emetogenic chemotherapy.
They found the data suggest “that NEPA, in a single dose, had equivalent efficacy to a 3-day oral aprepitant/granisetron regimen,” according to the lead investigator and abstract presenter.
Li Zhang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, presented the data at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Congress (abstract PS049, pp S55 – S56).
NEPA is a combination of the selective NK1RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3RA, palonosetron (0.5 mg) for the prevention of CINV.
Oral palonosetron prevents nausea and vomiting during the acute phase of treatment.
Netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.
It is formulated into a single oral capsule.
Study design
The study was a phase 3 randomized, double-blind, double-dummy study conducted in 828 chemotherapy-naïve Asian patients receiving cisplatin-based highly emetogenic chemotherapy (HEC) agents.
Patients received a single oral dose of NEPA on day 1 or a 3-day oral APR/GRAN regimen (days 1-3).
All patients received oral dexamethasone on days 1-4.
The primary efficacy endpoint was complete response (CR), defined as no emesis or rescue medication needed during the overall (0-120 hour) phase.
The investigators defined non-inferiority to be the lower limit of the two-sided 95% confidence interval greater than the non-inferiority margin set at ̶ 10%.
Secondary endpoints included no emesis, no rescue medication, and no significant nausea (NSN), defined as <25 mm on 100 mm visual analog scale (VAS).
Results
The baseline demographics were comparable between the NEPA (n=413) and APR/GRAN (n=416) arms: 71% of the patients were male, a mean age of 55 years, and a little more than half were ECOG performance status 1.
The most common cancer types were lung and head and neck cancer.
Patients had received a median cisplatin dose of 73 and 72 mg/m2 in the NEPA and APR/GRAN arms, respectively.
Within the first 24 hours (acute phase), NEPA was non-inferior to APR/GRAN. NEPA had a CR rate of 84.5% and APR/GRAN had a CR rate of 87.0%. The risk difference between the 2 agents was -2.5% (range, -7.2%, 2.3%).
In the delayed phase (25-120 hours), NEPA had a CR rate of 77.9% and APR/GRAN, 74.3%. The risk difference was 3.7% (range, -2.1%, 9.5%).
Overall, for both phases, the CR rate was 73.8% for NEPA and 72.4% for APR/GRAN. The risk difference was 1.5% (range, -4.5%, 7.5%).
Dr Zhang pointed out that although the overall CR rates were similar, the daily rates of patients experiencing CINV remained in the range of 13% - 15% for patients in the APR/GRAN arm.
However, daily rates of CINV for patients receiving NEPA declined from 16% to 8% over the 5 days. The investigators believe this suggests a benefit for delayed CINV.
Regarding secondary endpoints, significantly more patients receiving NEPA did not require rescue medication in the delayed phase and overall than patients in the APR/GRAN arm.
Treatment-emergent adverse events (TEAEs) were comparable between the arms—58.1% in the NEPA arm and 57.5% in the APR/GRAN arm, as were serious TEAS, at 4.5% and 4.6% for NEPA and APR/GRAN, respectively. And the no emesis and no significant nausea rates favored NEPA.
The most common treatment-emergent adverse events occurring in 2% or more of the patients in both arms were constipation and hiccups.
Two serious treatment-related adverse events occurred in each arm, 1 leading to discontinuation in the NEPA arm.
The investigators concluded that NEPA, as a convenient capsule administered once per cycle, is at least as effective as the 3-day regimen of APR/GRAN in patients receiving HEC.
NEPA (Akynzeo®) is approved by the US Food and Drug Administration and marketed globally by Helsinn, Lugano, Switzerland, the sponsor of the trial.
For the full US prescribing information, see the package insert.
Less is more in PET-negative, advanced HL
MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.” 
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.”
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.”
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
Brentuximab meets phase 3 primary endpoint in frontline advanced HL
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
CARs race for supremacy against aggressive non-Hodgkin lymphoma
MADRID – Two chimeric antigen receptor T cell (CAR-T) constructs are showing promising activity against treatment-refractory, aggressive forms of non-Hodgkin lymphoma in multicenter clinical trials.
In the ZUMA-1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T product, was associated with an 82% objective response rate (ORR), including 54% complete responses, in patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), reported Yi Lin, MD, PhD, from the Mayo Clinic in Rochester Minnesota.
In an interim analysis from the JULIET study, a different anti-CD19 CAR-T construct labeled CTL019 was associated with a 59% ORR, consisting of 43% complete responses and 16% partial responses (PR) in patients with relapsed or refractory DLBCL, reported Gilles Salles, MD, PhD, from the University of Lyon, France.
The analysis “confirms the high response rates and durable responses observed in the previous single-center trial,” Dr. Salles said.
Although the CAR-T cell constructs in the study have different costimulatory molecules, each is created in a centralized facility, which allows for consistent manufacturing of cells sufficient for harvesting, transfecting, expanding, and reinfusing into heavily pretreated patients.
The construct used in ZUMA-1, also called KTE-C19 (Kite Pharma), has CD28 and CD3-zeta signaling domains. CTL019 (Novarits, U. Pennsylvania, and Oxford Biomedica) has CD3-zeta and 4-1BB costimulatory domains.
ZUMA-1
Dr. Lin reported phase II results from ZUMA-1, investigating axi-cel at a target dose of 2 x 106 cells per kilogram in 72 patients with refractory DLBCL (cohort 1), and 20 patients with refractory PMBCL or TFL (cohort 2).
The median patient age was 58 years. Patients had stage III or IV disease, 47% had International Prognostic Index (IPI) scores of 3-4, 77% had disease that was refractory to second-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant
The axi-cel construct was successfully manufactured in 99% of patients, with an average turnaround time from apheresis to the clinical site of 17 days.
As noted before, the trial met its primary endpoint with an 82% ORR, consisting of 54% complete responses and 28% partial responses.
The median duration of response was 8.2 months, and for patients with complete responses the median duration has not been reached.
Median overall survival has also not been reached.
The treatment was generally safe, with only 13% of patients experiencing grade 3 or greater cytokine release syndrome (CRS), and 28% having grade 3 or greater neurologic events. The events were generally reversible, and the rates of each declined over time. The use of tociluzumab or steroids to control adverse events did not have a negative effect on responses, Dr. Lin said.
JULIET
In the ongoing JULIET study, patients with relapsed/refractory DLBCL after at least two prior lines of therapy and who are not candidates for stem cell transplants are enrolled.
In a safety analysis including 85 patients, the CRS was seen in 57% of all patients, including grade 3 in 17% and grade 4 in 9%.
Other common adverse events occurring within 8 weeks of CTL019 infusion were infections in 26% of patients, cytopenias lasting longer than 28 days in 26%, neurologic events in 21%, febrile neutropenia in 14%, and tumor lysis syndrome in 1%.
There were no cases of cerebral edema, and no deaths attributable to the CAR-T cell construct, Dr. Salles said.
Peter Borchmann, MD, from the University of Cologne, Germany, who attended the briefing but was not involved with either study, commented that investigators in ZUMA-1 need to monitor patients carefully, because previous clinical trials using other CAR-T cells with CD28 costimuatory domains have been associated with several cases of fatal cerebral edema.
“I think you can use CD28 in lymphoma, and it’s highly active as we have seen, but my personal impression is that you have to be aware that this might happen,” he said in an interview.
The ZUMA-1 study is funded by Kite Pharma. Dr. Lin disclosed research funding from Janssen. The JULIET study is supported by Novartis. Dr. Salles disclosed serving on an advisory board for the company. Dr. Borchmann had no disclosures.
MADRID – Two chimeric antigen receptor T cell (CAR-T) constructs are showing promising activity against treatment-refractory, aggressive forms of non-Hodgkin lymphoma in multicenter clinical trials.
In the ZUMA-1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T product, was associated with an 82% objective response rate (ORR), including 54% complete responses, in patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), reported Yi Lin, MD, PhD, from the Mayo Clinic in Rochester Minnesota.
In an interim analysis from the JULIET study, a different anti-CD19 CAR-T construct labeled CTL019 was associated with a 59% ORR, consisting of 43% complete responses and 16% partial responses (PR) in patients with relapsed or refractory DLBCL, reported Gilles Salles, MD, PhD, from the University of Lyon, France.
The analysis “confirms the high response rates and durable responses observed in the previous single-center trial,” Dr. Salles said.
Although the CAR-T cell constructs in the study have different costimulatory molecules, each is created in a centralized facility, which allows for consistent manufacturing of cells sufficient for harvesting, transfecting, expanding, and reinfusing into heavily pretreated patients.
The construct used in ZUMA-1, also called KTE-C19 (Kite Pharma), has CD28 and CD3-zeta signaling domains. CTL019 (Novarits, U. Pennsylvania, and Oxford Biomedica) has CD3-zeta and 4-1BB costimulatory domains.
ZUMA-1
Dr. Lin reported phase II results from ZUMA-1, investigating axi-cel at a target dose of 2 x 106 cells per kilogram in 72 patients with refractory DLBCL (cohort 1), and 20 patients with refractory PMBCL or TFL (cohort 2).
The median patient age was 58 years. Patients had stage III or IV disease, 47% had International Prognostic Index (IPI) scores of 3-4, 77% had disease that was refractory to second-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant
The axi-cel construct was successfully manufactured in 99% of patients, with an average turnaround time from apheresis to the clinical site of 17 days.
As noted before, the trial met its primary endpoint with an 82% ORR, consisting of 54% complete responses and 28% partial responses.
The median duration of response was 8.2 months, and for patients with complete responses the median duration has not been reached.
Median overall survival has also not been reached.
The treatment was generally safe, with only 13% of patients experiencing grade 3 or greater cytokine release syndrome (CRS), and 28% having grade 3 or greater neurologic events. The events were generally reversible, and the rates of each declined over time. The use of tociluzumab or steroids to control adverse events did not have a negative effect on responses, Dr. Lin said.
JULIET
In the ongoing JULIET study, patients with relapsed/refractory DLBCL after at least two prior lines of therapy and who are not candidates for stem cell transplants are enrolled.
In a safety analysis including 85 patients, the CRS was seen in 57% of all patients, including grade 3 in 17% and grade 4 in 9%.
Other common adverse events occurring within 8 weeks of CTL019 infusion were infections in 26% of patients, cytopenias lasting longer than 28 days in 26%, neurologic events in 21%, febrile neutropenia in 14%, and tumor lysis syndrome in 1%.
There were no cases of cerebral edema, and no deaths attributable to the CAR-T cell construct, Dr. Salles said.
Peter Borchmann, MD, from the University of Cologne, Germany, who attended the briefing but was not involved with either study, commented that investigators in ZUMA-1 need to monitor patients carefully, because previous clinical trials using other CAR-T cells with CD28 costimuatory domains have been associated with several cases of fatal cerebral edema.
“I think you can use CD28 in lymphoma, and it’s highly active as we have seen, but my personal impression is that you have to be aware that this might happen,” he said in an interview.
The ZUMA-1 study is funded by Kite Pharma. Dr. Lin disclosed research funding from Janssen. The JULIET study is supported by Novartis. Dr. Salles disclosed serving on an advisory board for the company. Dr. Borchmann had no disclosures.
MADRID – Two chimeric antigen receptor T cell (CAR-T) constructs are showing promising activity against treatment-refractory, aggressive forms of non-Hodgkin lymphoma in multicenter clinical trials.
In the ZUMA-1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR-T product, was associated with an 82% objective response rate (ORR), including 54% complete responses, in patients with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL), reported Yi Lin, MD, PhD, from the Mayo Clinic in Rochester Minnesota.
In an interim analysis from the JULIET study, a different anti-CD19 CAR-T construct labeled CTL019 was associated with a 59% ORR, consisting of 43% complete responses and 16% partial responses (PR) in patients with relapsed or refractory DLBCL, reported Gilles Salles, MD, PhD, from the University of Lyon, France.
The analysis “confirms the high response rates and durable responses observed in the previous single-center trial,” Dr. Salles said.
Although the CAR-T cell constructs in the study have different costimulatory molecules, each is created in a centralized facility, which allows for consistent manufacturing of cells sufficient for harvesting, transfecting, expanding, and reinfusing into heavily pretreated patients.
The construct used in ZUMA-1, also called KTE-C19 (Kite Pharma), has CD28 and CD3-zeta signaling domains. CTL019 (Novarits, U. Pennsylvania, and Oxford Biomedica) has CD3-zeta and 4-1BB costimulatory domains.
ZUMA-1
Dr. Lin reported phase II results from ZUMA-1, investigating axi-cel at a target dose of 2 x 106 cells per kilogram in 72 patients with refractory DLBCL (cohort 1), and 20 patients with refractory PMBCL or TFL (cohort 2).
The median patient age was 58 years. Patients had stage III or IV disease, 47% had International Prognostic Index (IPI) scores of 3-4, 77% had disease that was refractory to second-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant
The axi-cel construct was successfully manufactured in 99% of patients, with an average turnaround time from apheresis to the clinical site of 17 days.
As noted before, the trial met its primary endpoint with an 82% ORR, consisting of 54% complete responses and 28% partial responses.
The median duration of response was 8.2 months, and for patients with complete responses the median duration has not been reached.
Median overall survival has also not been reached.
The treatment was generally safe, with only 13% of patients experiencing grade 3 or greater cytokine release syndrome (CRS), and 28% having grade 3 or greater neurologic events. The events were generally reversible, and the rates of each declined over time. The use of tociluzumab or steroids to control adverse events did not have a negative effect on responses, Dr. Lin said.
JULIET
In the ongoing JULIET study, patients with relapsed/refractory DLBCL after at least two prior lines of therapy and who are not candidates for stem cell transplants are enrolled.
In a safety analysis including 85 patients, the CRS was seen in 57% of all patients, including grade 3 in 17% and grade 4 in 9%.
Other common adverse events occurring within 8 weeks of CTL019 infusion were infections in 26% of patients, cytopenias lasting longer than 28 days in 26%, neurologic events in 21%, febrile neutropenia in 14%, and tumor lysis syndrome in 1%.
There were no cases of cerebral edema, and no deaths attributable to the CAR-T cell construct, Dr. Salles said.
Peter Borchmann, MD, from the University of Cologne, Germany, who attended the briefing but was not involved with either study, commented that investigators in ZUMA-1 need to monitor patients carefully, because previous clinical trials using other CAR-T cells with CD28 costimuatory domains have been associated with several cases of fatal cerebral edema.
“I think you can use CD28 in lymphoma, and it’s highly active as we have seen, but my personal impression is that you have to be aware that this might happen,” he said in an interview.
The ZUMA-1 study is funded by Kite Pharma. Dr. Lin disclosed research funding from Janssen. The JULIET study is supported by Novartis. Dr. Salles disclosed serving on an advisory board for the company. Dr. Borchmann had no disclosures.
AT EHA 2017
Key clinical point: CAR-T cell therapies are showing good activity against relapsed/refractory non-Hodgkin lymphomas.
Major finding: In ZUMA-1, the objective response rate was 82%. In JULIET, it was 59%
Data source: Two multicenter trials of CAR-T cells in patients with relapsed/refractory DLBCL, PMBCL, and TFL.
Disclosures: The ZUMA-1 study is funded by Kite Pharma. Dr. Lin disclosed research funding from Janssen. The JULIET study is supported by Novartis. Dr. Salles disclosed serving on an advisory board for the company. Dr. Borchmann had no disclosures.
Overall survival better in advanced Hodgkin lymphoma with shorter eBEACOPP
MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.
Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.
“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.
Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.
To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.
A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.
After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.
The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.
The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.
Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).
In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.
There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.
In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.
The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.
MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.
Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.
“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.
Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.
To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.
A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.
After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.
The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.
The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.
Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).
In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.
There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.
In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.
The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.
MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.
Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.
“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.
Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.
To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.
A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.
After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.
The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.
The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.
Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).
In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.
There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.
In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.
The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.
AT EHA 2017
Key clinical point: For patients with newly diagnosed advanced Hodgkin lymphoma with PET-confirmed metabolic responses, four cycles of BEACOPP were at least as good as six to eight cycles for progression-free and overall survival.
Major finding: 5-year overall survival with four cycles of extended-dose BEACOPP was 97.6%, compared with. 95.4% for six to eight cycles (P = .006).
Data source: Randomized trial in 1,005 patients with newly diagnosed Hodgkin lymphoma from five European nations.
Disclosures: The study was supported by German Cancer Aid, the Swiss State Secretariate for Education, Research and Innovation, and by Roche Pharma AG. Dr. Borchmann reported having no relevant disclosures.
New frontline treatments needed for Hodgkin lymphoma
In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.
Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.
Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).
Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.1 Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.
Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,2-4 underlining the challenges of treating later stage Hodgkin lymphoma.
Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)5-6— a historically and frequently used treatment regimen.
These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.7-10
With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.8-15
Advanced stage vs early stage Hodgkin lymphoma
Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,7,15-16 with nearly one third remaining uncured following standard frontline therapy.7-10
As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.16
The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.16
Unmet needs with current frontline Hodgkin lymphoma treatment
Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.
ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.17
Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.8-10,13,18
Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.19
Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.8-10,13-15
Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,20 is also associated with an increased risk of secondary cancers and cardiotoxicity.8-10,21
With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.
For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.8-10,12-15,22
Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.23-25 These secondary effects can affect a patient’s quality of life8-9,12,14-15,22,26-28 and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.22
Studies have shown that most relapses after ASCT typically occur within 2 years.29 After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.22,26,30
Goals of clinical research
Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.
Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities.
Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
______________________________________________________
1American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.
2Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.
3American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.
4Fermé C, et al. New Engl J Med, 2007.357:1916–27.
5Sureda A, et al. Ann Oncol, 2005;16: 625–633.
6Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.
7Gordon LI, et al. J Clin Oncol, 2013;31:684-691.
8Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.
9Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554
10Viviani S, et al. New Engl J Med, 2011;365(3):203-212.
11Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232
12Behringer K, et al. J Clin Oncol, 2013;31:231-239.
13Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.
14Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.
15Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.
16Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260
17Ansell SM. American Journal of Hematology, 2014;89: 771–779.
18Merli F, et al. J Clin Oncol, 34:1175-1181.
19Johnson P, et al. N Engl J Med. 2016;374:2419‑2429
20American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.
21Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.
22Khimani N, et al. Ann Oncol, 2013;24(1):226-230.
23Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.
24Evens AM, et al. Br J Haematol, 2013;161: 76–86.
25Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.
26Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.
27Daniels LA, et al. Br J Cancer 2014;110:868-874.
28Loge JH, et al. Ann Oncol. 1999;10:71-77.
29Brusamolino E, Carella AM. Haematologica, 2007;92:6-10
30Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.
In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.
Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.
Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).
Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.1 Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.
Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,2-4 underlining the challenges of treating later stage Hodgkin lymphoma.
Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)5-6— a historically and frequently used treatment regimen.
These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.7-10
With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.8-15
Advanced stage vs early stage Hodgkin lymphoma
Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,7,15-16 with nearly one third remaining uncured following standard frontline therapy.7-10
As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.16
The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.16
Unmet needs with current frontline Hodgkin lymphoma treatment
Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.
ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.17
Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.8-10,13,18
Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.19
Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.8-10,13-15
Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,20 is also associated with an increased risk of secondary cancers and cardiotoxicity.8-10,21
With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.
For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.8-10,12-15,22
Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.23-25 These secondary effects can affect a patient’s quality of life8-9,12,14-15,22,26-28 and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.22
Studies have shown that most relapses after ASCT typically occur within 2 years.29 After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.22,26,30
Goals of clinical research
Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.
Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities.
Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
______________________________________________________
1American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.
2Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.
3American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.
4Fermé C, et al. New Engl J Med, 2007.357:1916–27.
5Sureda A, et al. Ann Oncol, 2005;16: 625–633.
6Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.
7Gordon LI, et al. J Clin Oncol, 2013;31:684-691.
8Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.
9Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554
10Viviani S, et al. New Engl J Med, 2011;365(3):203-212.
11Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232
12Behringer K, et al. J Clin Oncol, 2013;31:231-239.
13Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.
14Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.
15Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.
16Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260
17Ansell SM. American Journal of Hematology, 2014;89: 771–779.
18Merli F, et al. J Clin Oncol, 34:1175-1181.
19Johnson P, et al. N Engl J Med. 2016;374:2419‑2429
20American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.
21Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.
22Khimani N, et al. Ann Oncol, 2013;24(1):226-230.
23Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.
24Evens AM, et al. Br J Haematol, 2013;161: 76–86.
25Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.
26Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.
27Daniels LA, et al. Br J Cancer 2014;110:868-874.
28Loge JH, et al. Ann Oncol. 1999;10:71-77.
29Brusamolino E, Carella AM. Haematologica, 2007;92:6-10
30Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.
In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.
Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.
Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).
Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.1 Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.
Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,2-4 underlining the challenges of treating later stage Hodgkin lymphoma.
Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)5-6— a historically and frequently used treatment regimen.
These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.7-10
With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.8-15
Advanced stage vs early stage Hodgkin lymphoma
Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,7,15-16 with nearly one third remaining uncured following standard frontline therapy.7-10
As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.16
The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.16
Unmet needs with current frontline Hodgkin lymphoma treatment
Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.
ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.17
Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.8-10,13,18
Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.19
Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.8-10,13-15
Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,20 is also associated with an increased risk of secondary cancers and cardiotoxicity.8-10,21
With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.
For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.8-10,12-15,22
Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.23-25 These secondary effects can affect a patient’s quality of life8-9,12,14-15,22,26-28 and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.22
Studies have shown that most relapses after ASCT typically occur within 2 years.29 After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.22,26,30
Goals of clinical research
Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.
Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities.
Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
______________________________________________________
1American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.
2Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.
3American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.
4Fermé C, et al. New Engl J Med, 2007.357:1916–27.
5Sureda A, et al. Ann Oncol, 2005;16: 625–633.
6Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.
7Gordon LI, et al. J Clin Oncol, 2013;31:684-691.
8Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.
9Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554
10Viviani S, et al. New Engl J Med, 2011;365(3):203-212.
11Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232
12Behringer K, et al. J Clin Oncol, 2013;31:231-239.
13Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.
14Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.
15Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.
16Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260
17Ansell SM. American Journal of Hematology, 2014;89: 771–779.
18Merli F, et al. J Clin Oncol, 34:1175-1181.
19Johnson P, et al. N Engl J Med. 2016;374:2419‑2429
20American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.
21Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.
22Khimani N, et al. Ann Oncol, 2013;24(1):226-230.
23Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.
24Evens AM, et al. Br J Haematol, 2013;161: 76–86.
25Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.
26Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.
27Daniels LA, et al. Br J Cancer 2014;110:868-874.
28Loge JH, et al. Ann Oncol. 1999;10:71-77.
29Brusamolino E, Carella AM. Haematologica, 2007;92:6-10
30Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.
Severe health conditions decrease among childhood cancer survivors
CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).
Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.
Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.
Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.
Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.
The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).
The investigators found significant decreases in severe health conditions in 6 diagnostic groups:
- Wilms tumor, decreased from 13% to 5% (P<0.0001)
- HL, decreased from 18% to 11% (P<0.0001)
- Astrocytoma, decreased from 15% to 9% (P=0.004)
- NHL, decreased from 10% to 6% (P=0.04)
- ALL, decreased from 9% to 7% (P=0.002)
- Ewings sarcoma, decreased from 19% to 10% (P=0.01)
They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.
The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.
They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.
The National Institutes of Health funded the study.
CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).
Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.
Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.
Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.
Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.
The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).
The investigators found significant decreases in severe health conditions in 6 diagnostic groups:
- Wilms tumor, decreased from 13% to 5% (P<0.0001)
- HL, decreased from 18% to 11% (P<0.0001)
- Astrocytoma, decreased from 15% to 9% (P=0.004)
- NHL, decreased from 10% to 6% (P=0.04)
- ALL, decreased from 9% to 7% (P=0.002)
- Ewings sarcoma, decreased from 19% to 10% (P=0.01)
They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.
The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.
They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.
The National Institutes of Health funded the study.
CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).
Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.
Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.
Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.
Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.
The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).
The investigators found significant decreases in severe health conditions in 6 diagnostic groups:
- Wilms tumor, decreased from 13% to 5% (P<0.0001)
- HL, decreased from 18% to 11% (P<0.0001)
- Astrocytoma, decreased from 15% to 9% (P=0.004)
- NHL, decreased from 10% to 6% (P=0.04)
- ALL, decreased from 9% to 7% (P=0.002)
- Ewings sarcoma, decreased from 19% to 10% (P=0.01)
They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.
The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.
They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.
The National Institutes of Health funded the study.
Severe health conditions decline in childhood cancer survivors
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.
For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.
The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.
As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.
By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.
Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).
The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).
Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.
[email protected]
On Twitter @maryjodales
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.
For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.
The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.
As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.
By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.
Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).
The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).
Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.
[email protected]
On Twitter @maryjodales
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.
For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.
The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.
As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.
By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.
Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).
The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).
Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.
[email protected]
On Twitter @maryjodales
AT ASCO 2017
Key clinical point:
Major finding: For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: HR, 0.84 [95% CI, 0.80-0.89]).
Data source: An analysis of 23,600 participants in the Childhood Cancer Survivor Study.
Disclosures: The study was funded by the National Institutes of Health.
Global study reveals healthcare inequity, preventable deaths
A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.
“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.
“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”
Dr Murray and his colleagues reported these findings in The Lancet.
For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.
The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.
Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.
In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.
Results
The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.
In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.
The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.
Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.
However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.
‘Developed’ nations falling short
The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.
However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).
“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.
“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”
Other nations with strong economies and advanced medical technology are falling short in some areas as well.
For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.
“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?”
*The 32 causes are:
- Adverse effects of medical treatment
- Appendicitis
- Breast cancer
- Cerebrovascular disease (stroke)
- Cervical cancer
- Chronic kidney disease
- Chronic respiratory diseases
- Colon and rectum cancer
- Congenital anomalies
- Diabetes mellitus
- Diarrhea-related diseases
- Diphtheria
- Epilepsy
- Gallbladder and biliary diseases
- Hodgkin lymphoma
- Hypertensive heart disease
- Inguinal, femoral, and abdominal hernia
- Ischemic heart disease
- Leukemia
- Lower respiratory infections
- Maternal disorders
- Measles
- Neonatal disorders
- Non-melanoma skin cancer
- Peptic ulcer disease
- Rheumatic heart disease
- Testicular cancer
- Tetanus
- Tuberculosis
- Upper respiratory infections
- Uterine cancer
- Whooping cough.
A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.
“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.
“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”
Dr Murray and his colleagues reported these findings in The Lancet.
For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.
The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.
Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.
In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.
Results
The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.
In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.
The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.
Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.
However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.
‘Developed’ nations falling short
The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.
However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).
“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.
“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”
Other nations with strong economies and advanced medical technology are falling short in some areas as well.
For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.
“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?”
*The 32 causes are:
- Adverse effects of medical treatment
- Appendicitis
- Breast cancer
- Cerebrovascular disease (stroke)
- Cervical cancer
- Chronic kidney disease
- Chronic respiratory diseases
- Colon and rectum cancer
- Congenital anomalies
- Diabetes mellitus
- Diarrhea-related diseases
- Diphtheria
- Epilepsy
- Gallbladder and biliary diseases
- Hodgkin lymphoma
- Hypertensive heart disease
- Inguinal, femoral, and abdominal hernia
- Ischemic heart disease
- Leukemia
- Lower respiratory infections
- Maternal disorders
- Measles
- Neonatal disorders
- Non-melanoma skin cancer
- Peptic ulcer disease
- Rheumatic heart disease
- Testicular cancer
- Tetanus
- Tuberculosis
- Upper respiratory infections
- Uterine cancer
- Whooping cough.
A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.
“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.
“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”
Dr Murray and his colleagues reported these findings in The Lancet.
For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.
The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.
Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.
In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.
Results
The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.
In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.
The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.
Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.
However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.
‘Developed’ nations falling short
The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.
However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).
“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.
“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”
Other nations with strong economies and advanced medical technology are falling short in some areas as well.
For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.
“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?”
*The 32 causes are:
- Adverse effects of medical treatment
- Appendicitis
- Breast cancer
- Cerebrovascular disease (stroke)
- Cervical cancer
- Chronic kidney disease
- Chronic respiratory diseases
- Colon and rectum cancer
- Congenital anomalies
- Diabetes mellitus
- Diarrhea-related diseases
- Diphtheria
- Epilepsy
- Gallbladder and biliary diseases
- Hodgkin lymphoma
- Hypertensive heart disease
- Inguinal, femoral, and abdominal hernia
- Ischemic heart disease
- Leukemia
- Lower respiratory infections
- Maternal disorders
- Measles
- Neonatal disorders
- Non-melanoma skin cancer
- Peptic ulcer disease
- Rheumatic heart disease
- Testicular cancer
- Tetanus
- Tuberculosis
- Upper respiratory infections
- Uterine cancer
- Whooping cough.
HL survivors should be screened for CAD after chest irradiation
VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.
The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.
These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.
The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).
“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.
“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”
Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.
The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.
CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.
Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.
Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).
Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).
The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).
Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.
Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).
“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.
“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”
“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”
Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.
He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.
“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”
“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.”
VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.
The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.
These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.
The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).
“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.
“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”
Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.
The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.
CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.
Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.
Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).
Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).
The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).
Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.
Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).
“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.
“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”
“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”
Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.
He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.
“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”
“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.”
VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.
The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.
These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.
The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).
“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.
“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”
Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.
The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.
CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.
Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.
Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).
Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).
The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).
Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.
Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).
“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.
“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”
“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”
Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.
He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.
“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”
“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.”