Indolent Lymphoma

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

CHICAGO – Progression-free survival for patients with rituximab-refractory indolent non-Hodgkin’s lymphomas was effectively doubled with a combination of obinutuzumab and bendamustine, compared with bendamustine alone.

Dr. Laura Helen Sehn from the British Columbia (Canada) Cancer Agency in Vancouver, says that the study, the GADOLIN trial. “is remarkable, because it does demonstrate the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibiody for patients who are rituximab refractory.”

She described the study’s key findings at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Progression-free survival for patients with rituximab-refractory indolent non-Hodgkin’s lymphomas was effectively doubled with a combination of obinutuzumab and bendamustine, compared with bendamustine alone.

Dr. Laura Helen Sehn from the British Columbia (Canada) Cancer Agency in Vancouver, says that the study, the GADOLIN trial. “is remarkable, because it does demonstrate the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibiody for patients who are rituximab refractory.”

She described the study’s key findings at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Progression-free survival for patients with rituximab-refractory indolent non-Hodgkin’s lymphomas was effectively doubled with a combination of obinutuzumab and bendamustine, compared with bendamustine alone.

Dr. Laura Helen Sehn from the British Columbia (Canada) Cancer Agency in Vancouver, says that the study, the GADOLIN trial. “is remarkable, because it does demonstrate the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibiody for patients who are rituximab refractory.”

She described the study’s key findings at the annual meeting of the American Society of Clinical Oncology.

Ibrutinib proved to be “highly active” against refractory Waldenstrom’s macroglobulinemia in the first clinical trial to assess the agent’s safety and efficacy in this patient population, producing an overall response rate of 90.5% and a major response rate of 73.0% in a series of 63 consecutive patients, according to a report published online April 9 in the New England Journal of Medicine.

Waldenstrom’s macroglobulinemia is a malignant B-cell lymphoma in which whole-genome sequencing has revealed several activating mutations. Ibrutinib – an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is activated in tumor cells by some of these mutations – was found to trigger apoptosis of Waldenstrom’s macroglobulinemia cells in vitro and to show clinical activity in a phase I study. Investigators now report their findings from a prospective, industry-sponsored study of adults enrolled at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, and Stanford University Medical Center during a 1-year period and followed up for another 18 months.

All the participants had progressive disease at baseline despite receiving previous treatments including monoclonal antibodies, glucocorticoids, proteasome inhibitors, alkylators, immunomodulators, anthracyclines, and experimental therapies. Ibrutinib was taken orally every day for 26 4-week cycles until disease progressed or unacceptable toxic effects developed; treatment responders were permitted to continue the therapy after that time, if they wished, said Dr. Steven P. Treon of the Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, and his associates.

The primary objective of the study was to determine the overall rate of any treatment response (it was 90.5%) and the rate of major treatment response, defined as a 50% or greater decline in serum IgM levels (it was 73.0%). In addition, at 24 months, the progression-free survival was 69.1% and the overall survival was 95.2%. In comparison, previous studies of other monotherapies have shown overall response rates of only 40%-80% and median progression-free survival of only 8-20 months, the investigators said (N. Engl. J. Med. 2015 April 9 [doi:10.1056/NEJMoa1501548]).

Treatment response was rapid, with a median onset at 4 weeks, and both serum IgM and hemoglobin levels improved even in patients who showed modest or no changes in bone marrow disease burden. “This suggests that a mechanism other than tumor debulking could contribute to the clinical benefit with ibrutinib,” they added.

On CT imaging, 68% of patients showed decreased or resolved adenopathy and 57% showed decreased splenomegaly. Malignant pleural effusions resolved in two of three patients who had them, and peripheral neuropathy stabilized or improved in all nine who were affected. The latter result is “particularly encouraging given the challenging nature of treating IgM-related peripheral neuropathy in Waldenstrom’s macroglobulinemia,” Dr. Treon and his associates noted.

The toxic effects of treatment were moderate in these heavily pretreated patients and included neutropenia (22% of patients), thrombocytopenia (14%), bleeding events (3%), and reversible atrial fibrillation (5%) in patients with a history of arrhythmia. There were few infections, and no unexpected toxicities occurred, the investigators reported.

This study was supported by Pharmacyclics and Janssen Pharmaceuticals; with additional funding by Peter S. Bing, M.D.; the International Waldenstrom’s Macroglobulinemia Foundation; the Leukemia and Lymphoma Society; the Linda and Edward Nelson Fund for Waldenstrom’s Macroglobulinemia Research; the D’Amato Family Fund for Genomic Discovery; the Coyote Fund; and the Bauman Family Foundation. Dr. Treon reported ties to Pharmacyclics and Janssen; his associates reported ties to several industry sources.

Ibrutinib proved to be “highly active” against refractory Waldenstrom’s macroglobulinemia in the first clinical trial to assess the agent’s safety and efficacy in this patient population, producing an overall response rate of 90.5% and a major response rate of 73.0% in a series of 63 consecutive patients, according to a report published online April 9 in the New England Journal of Medicine.

Waldenstrom’s macroglobulinemia is a malignant B-cell lymphoma in which whole-genome sequencing has revealed several activating mutations. Ibrutinib – an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is activated in tumor cells by some of these mutations – was found to trigger apoptosis of Waldenstrom’s macroglobulinemia cells in vitro and to show clinical activity in a phase I study. Investigators now report their findings from a prospective, industry-sponsored study of adults enrolled at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, and Stanford University Medical Center during a 1-year period and followed up for another 18 months.

All the participants had progressive disease at baseline despite receiving previous treatments including monoclonal antibodies, glucocorticoids, proteasome inhibitors, alkylators, immunomodulators, anthracyclines, and experimental therapies. Ibrutinib was taken orally every day for 26 4-week cycles until disease progressed or unacceptable toxic effects developed; treatment responders were permitted to continue the therapy after that time, if they wished, said Dr. Steven P. Treon of the Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, and his associates.

The primary objective of the study was to determine the overall rate of any treatment response (it was 90.5%) and the rate of major treatment response, defined as a 50% or greater decline in serum IgM levels (it was 73.0%). In addition, at 24 months, the progression-free survival was 69.1% and the overall survival was 95.2%. In comparison, previous studies of other monotherapies have shown overall response rates of only 40%-80% and median progression-free survival of only 8-20 months, the investigators said (N. Engl. J. Med. 2015 April 9 [doi:10.1056/NEJMoa1501548]).

Treatment response was rapid, with a median onset at 4 weeks, and both serum IgM and hemoglobin levels improved even in patients who showed modest or no changes in bone marrow disease burden. “This suggests that a mechanism other than tumor debulking could contribute to the clinical benefit with ibrutinib,” they added.

On CT imaging, 68% of patients showed decreased or resolved adenopathy and 57% showed decreased splenomegaly. Malignant pleural effusions resolved in two of three patients who had them, and peripheral neuropathy stabilized or improved in all nine who were affected. The latter result is “particularly encouraging given the challenging nature of treating IgM-related peripheral neuropathy in Waldenstrom’s macroglobulinemia,” Dr. Treon and his associates noted.

The toxic effects of treatment were moderate in these heavily pretreated patients and included neutropenia (22% of patients), thrombocytopenia (14%), bleeding events (3%), and reversible atrial fibrillation (5%) in patients with a history of arrhythmia. There were few infections, and no unexpected toxicities occurred, the investigators reported.

This study was supported by Pharmacyclics and Janssen Pharmaceuticals; with additional funding by Peter S. Bing, M.D.; the International Waldenstrom’s Macroglobulinemia Foundation; the Leukemia and Lymphoma Society; the Linda and Edward Nelson Fund for Waldenstrom’s Macroglobulinemia Research; the D’Amato Family Fund for Genomic Discovery; the Coyote Fund; and the Bauman Family Foundation. Dr. Treon reported ties to Pharmacyclics and Janssen; his associates reported ties to several industry sources.

Ibrutinib proved to be “highly active” against refractory Waldenstrom’s macroglobulinemia in the first clinical trial to assess the agent’s safety and efficacy in this patient population, producing an overall response rate of 90.5% and a major response rate of 73.0% in a series of 63 consecutive patients, according to a report published online April 9 in the New England Journal of Medicine.

Waldenstrom’s macroglobulinemia is a malignant B-cell lymphoma in which whole-genome sequencing has revealed several activating mutations. Ibrutinib – an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is activated in tumor cells by some of these mutations – was found to trigger apoptosis of Waldenstrom’s macroglobulinemia cells in vitro and to show clinical activity in a phase I study. Investigators now report their findings from a prospective, industry-sponsored study of adults enrolled at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, and Stanford University Medical Center during a 1-year period and followed up for another 18 months.

All the participants had progressive disease at baseline despite receiving previous treatments including monoclonal antibodies, glucocorticoids, proteasome inhibitors, alkylators, immunomodulators, anthracyclines, and experimental therapies. Ibrutinib was taken orally every day for 26 4-week cycles until disease progressed or unacceptable toxic effects developed; treatment responders were permitted to continue the therapy after that time, if they wished, said Dr. Steven P. Treon of the Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, and his associates.

The primary objective of the study was to determine the overall rate of any treatment response (it was 90.5%) and the rate of major treatment response, defined as a 50% or greater decline in serum IgM levels (it was 73.0%). In addition, at 24 months, the progression-free survival was 69.1% and the overall survival was 95.2%. In comparison, previous studies of other monotherapies have shown overall response rates of only 40%-80% and median progression-free survival of only 8-20 months, the investigators said (N. Engl. J. Med. 2015 April 9 [doi:10.1056/NEJMoa1501548]).

Treatment response was rapid, with a median onset at 4 weeks, and both serum IgM and hemoglobin levels improved even in patients who showed modest or no changes in bone marrow disease burden. “This suggests that a mechanism other than tumor debulking could contribute to the clinical benefit with ibrutinib,” they added.

On CT imaging, 68% of patients showed decreased or resolved adenopathy and 57% showed decreased splenomegaly. Malignant pleural effusions resolved in two of three patients who had them, and peripheral neuropathy stabilized or improved in all nine who were affected. The latter result is “particularly encouraging given the challenging nature of treating IgM-related peripheral neuropathy in Waldenstrom’s macroglobulinemia,” Dr. Treon and his associates noted.

The toxic effects of treatment were moderate in these heavily pretreated patients and included neutropenia (22% of patients), thrombocytopenia (14%), bleeding events (3%), and reversible atrial fibrillation (5%) in patients with a history of arrhythmia. There were few infections, and no unexpected toxicities occurred, the investigators reported.

This study was supported by Pharmacyclics and Janssen Pharmaceuticals; with additional funding by Peter S. Bing, M.D.; the International Waldenstrom’s Macroglobulinemia Foundation; the Leukemia and Lymphoma Society; the Linda and Edward Nelson Fund for Waldenstrom’s Macroglobulinemia Research; the D’Amato Family Fund for Genomic Discovery; the Coyote Fund; and the Bauman Family Foundation. Dr. Treon reported ties to Pharmacyclics and Janssen; his associates reported ties to several industry sources.

Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.^1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.^2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
 

Click on the PDF icon at the top of this introduction to read the full article.

Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.^1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.^2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
 

Click on the PDF icon at the top of this introduction to read the full article.

Diffuse large B-cell lymphoma of the lung is a rare entity, and although the prognosis is favorable, its biological features, clinical presentation, prognostic markers, and treatment have not been well defined.^1,2 It is the second most common primary pulmonary lymphoma after mucosa-associated lymphoid tissue. PPL itself is very rare; it represents 3%-4% of extranodal non-Hodgkin lymphoma, less than 1% of NHL, and 0.5%-1.0% of primary pulmonary malignancies.^2,3 A review of the literature indicates a lack of data on pulmonary DLBCL. The objective of this case report is to highlight areas in which further research may be pursued to better understand this disease.
 

Click on the PDF icon at the top of this introduction to read the full article.

CHICAGO – Routine surveillance imaging does not improve clinical outcomes in patients with classic Hodgkin disease who are in first complete remission and it sharply increases costs, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The team, led by Dr. Sai Ravi Pingali, retrospectively reviewed the charts of 241 adult patients who achieved a complete remission after first-line therapy.

In 68%, the treating physicians’ planned approach was routine surveillance imaging, which consisted of radiologic imaging with scans every few months, plus clinical exams and laboratory testing. In the other 32%, the planned approach was clinical surveillance, meaning that radiologic imaging was performed only if concerning signs or symptoms occurred.

The two groups had statistically indistinguishable overall survival, and in both groups, all patients experiencing relapse successfully achieved a second complete remission with salvage therapy.

In the routinely imaged group, scanning increased costs by nearly $20,000 per patient and by almost $600,000 per each relapse detected. In addition, patients were exposed to the associated radiation.

"We were unable to detect an overall survival benefit associated with routine surveillance imaging, although I have to acknowledge that our study was limited in power given the small number of deaths and relapses," commented Dr. Pingali, an oncologist with the Medical College of Wisconsin Affiliated Hospitals in Milwaukee.

"Relapses in both ... groups were effectively salvaged with autologous stem cell transplantation, arguing against a critical advantage of detection of asymptomatic relapse. Also, we need to keep in mind that the costs associated with routine surveillance imaging are significant, and it is also associated with potential risks, both in terms of radiation exposure and unnecessary work-up," he added.

"We do not feel that potential risks and costs without overall survival benefit or any other clinical benefit justify the practice of routine surveillance imaging in classical Hodgkin lymphoma patients who have achieved a complete remission after first-line therapy. We recommend that such patients be followed clinically," Dr. Pingali concluded.

Invited discussant Dr. Leo Gordon of Northwestern University in Chicago, agreed that accumulating data argue against routine imaging for surveillance in this context and noted that insurers will likely not continue to cover scans having no proven benefit. The data should prompt a revision of guidelines and reeducation of clinicians and patients, he said.

"For translational researchers and investigators and academics, I think we need to convince journal reviewers that a manuscript is acceptable if scans are not so frequent. And for industry trials, I think we need to discuss with the Food and Drug Administration the endpoint of progression-free survival and that those endpoints may not only be driven by scans but by more mundane parameters," he said—namely, the history and physical examination.

But session comoderator Dr. Gilles A. Salles of Hospices Civils de Lyon, Université Claude Bernard, France, expressed reservations, noting that the study did not provide information on how patients were allocated to groups and the time frame of relapse.

"It may be different whether relapses occur early, in the first year, or they occur later, and that may have some implications for the surveillance," he said. "I understand that you and many others jumped over the idea that we should immediately stop. A few people may think that we need more solid data, despite the provocative and quality data that were presented, to really make this jump in clinical practice. That’s my personal opinion."

Dr. Pingali and his team retrospectively reviewed the charts of adult patients who received a new diagnosis of classical Hodgkin lymphoma between 2000 and 2010 at three institutions, achieved complete remission after first-line therapy and had at least 2 years of follow-up.

The routine surveillance imaging and clinical surveillance groups had similar demographic and disease characteristics, Dr. Pingali reported. The former were significantly more likely to have received ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) and less likely to have received the Stanford V regimen as first-line therapy, and they were significantly less likely to have received radiation therapy.

With a median duration of follow-up of about 4 years, the groups did not differ significantly with respect to overall survival. "When we look at the 5-year time point, when typically the surveillance CT scans are discontinued, the curves are pretty much superimposable," he pointed out.

There were five deaths in the routine surveillance imaging group, one of which was from relapsed disease; the other deaths were from cancer, heart failure, hip fracture, and myelodysplastic syndrome. There were four deaths in the clinical surveillance group: two were from non-Hodgkin lymphoma and two from unknown causes while the patient was in confirmed remission.

All of the six patients in the routinely imaged group and all of the five patients in the clinically followed group experiencing a relapse achieved another complete remission with second-line therapy.

The mean number of scans received was 1.14 in the clinical surveillance group – usually the scan performed after first-line treatment to confirm remission, according to Dr. Pingali – and 4.25 in the routine surveillance imaging group. The ratio of scans to detected relapses was 18 vs. 124.

The extra charges incurred from scans using the routine surveillance imaging approach were $18,896/patient and $593,698/relapse.

"It is important to note that this does not include additional costs from the work-up of the false-positive scans and also the wages lost," he noted.

Dr. Pingali disclosed no relevant conflicts of interest. Dr. Gordon disclosed that he receives honoraria from Genentech and research funding from Millennium and Pharmacyclics. Dr. Salles disclosed serving as an advisor or consultant for Calistoga Pharmaceuticals, Celgene; Genentech, Janssen Pharmaceutica, and Roche. He has served as a speaker or a member of a speakers bureau and has received grants for clinical research from Celgene and Roche.

CHICAGO – Routine surveillance imaging does not improve clinical outcomes in patients with classic Hodgkin disease who are in first complete remission and it sharply increases costs, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The team, led by Dr. Sai Ravi Pingali, retrospectively reviewed the charts of 241 adult patients who achieved a complete remission after first-line therapy.

In 68%, the treating physicians’ planned approach was routine surveillance imaging, which consisted of radiologic imaging with scans every few months, plus clinical exams and laboratory testing. In the other 32%, the planned approach was clinical surveillance, meaning that radiologic imaging was performed only if concerning signs or symptoms occurred.

The two groups had statistically indistinguishable overall survival, and in both groups, all patients experiencing relapse successfully achieved a second complete remission with salvage therapy.

In the routinely imaged group, scanning increased costs by nearly $20,000 per patient and by almost $600,000 per each relapse detected. In addition, patients were exposed to the associated radiation.

"We were unable to detect an overall survival benefit associated with routine surveillance imaging, although I have to acknowledge that our study was limited in power given the small number of deaths and relapses," commented Dr. Pingali, an oncologist with the Medical College of Wisconsin Affiliated Hospitals in Milwaukee.

"Relapses in both ... groups were effectively salvaged with autologous stem cell transplantation, arguing against a critical advantage of detection of asymptomatic relapse. Also, we need to keep in mind that the costs associated with routine surveillance imaging are significant, and it is also associated with potential risks, both in terms of radiation exposure and unnecessary work-up," he added.

"We do not feel that potential risks and costs without overall survival benefit or any other clinical benefit justify the practice of routine surveillance imaging in classical Hodgkin lymphoma patients who have achieved a complete remission after first-line therapy. We recommend that such patients be followed clinically," Dr. Pingali concluded.

Invited discussant Dr. Leo Gordon of Northwestern University in Chicago, agreed that accumulating data argue against routine imaging for surveillance in this context and noted that insurers will likely not continue to cover scans having no proven benefit. The data should prompt a revision of guidelines and reeducation of clinicians and patients, he said.

"For translational researchers and investigators and academics, I think we need to convince journal reviewers that a manuscript is acceptable if scans are not so frequent. And for industry trials, I think we need to discuss with the Food and Drug Administration the endpoint of progression-free survival and that those endpoints may not only be driven by scans but by more mundane parameters," he said—namely, the history and physical examination.

But session comoderator Dr. Gilles A. Salles of Hospices Civils de Lyon, Université Claude Bernard, France, expressed reservations, noting that the study did not provide information on how patients were allocated to groups and the time frame of relapse.

"It may be different whether relapses occur early, in the first year, or they occur later, and that may have some implications for the surveillance," he said. "I understand that you and many others jumped over the idea that we should immediately stop. A few people may think that we need more solid data, despite the provocative and quality data that were presented, to really make this jump in clinical practice. That’s my personal opinion."

Dr. Pingali and his team retrospectively reviewed the charts of adult patients who received a new diagnosis of classical Hodgkin lymphoma between 2000 and 2010 at three institutions, achieved complete remission after first-line therapy and had at least 2 years of follow-up.

The routine surveillance imaging and clinical surveillance groups had similar demographic and disease characteristics, Dr. Pingali reported. The former were significantly more likely to have received ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) and less likely to have received the Stanford V regimen as first-line therapy, and they were significantly less likely to have received radiation therapy.

With a median duration of follow-up of about 4 years, the groups did not differ significantly with respect to overall survival. "When we look at the 5-year time point, when typically the surveillance CT scans are discontinued, the curves are pretty much superimposable," he pointed out.

There were five deaths in the routine surveillance imaging group, one of which was from relapsed disease; the other deaths were from cancer, heart failure, hip fracture, and myelodysplastic syndrome. There were four deaths in the clinical surveillance group: two were from non-Hodgkin lymphoma and two from unknown causes while the patient was in confirmed remission.

All of the six patients in the routinely imaged group and all of the five patients in the clinically followed group experiencing a relapse achieved another complete remission with second-line therapy.

The mean number of scans received was 1.14 in the clinical surveillance group – usually the scan performed after first-line treatment to confirm remission, according to Dr. Pingali – and 4.25 in the routine surveillance imaging group. The ratio of scans to detected relapses was 18 vs. 124.

The extra charges incurred from scans using the routine surveillance imaging approach were $18,896/patient and $593,698/relapse.

"It is important to note that this does not include additional costs from the work-up of the false-positive scans and also the wages lost," he noted.

Dr. Pingali disclosed no relevant conflicts of interest. Dr. Gordon disclosed that he receives honoraria from Genentech and research funding from Millennium and Pharmacyclics. Dr. Salles disclosed serving as an advisor or consultant for Calistoga Pharmaceuticals, Celgene; Genentech, Janssen Pharmaceutica, and Roche. He has served as a speaker or a member of a speakers bureau and has received grants for clinical research from Celgene and Roche.

CHICAGO – Routine surveillance imaging does not improve clinical outcomes in patients with classic Hodgkin disease who are in first complete remission and it sharply increases costs, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The team, led by Dr. Sai Ravi Pingali, retrospectively reviewed the charts of 241 adult patients who achieved a complete remission after first-line therapy.

In 68%, the treating physicians’ planned approach was routine surveillance imaging, which consisted of radiologic imaging with scans every few months, plus clinical exams and laboratory testing. In the other 32%, the planned approach was clinical surveillance, meaning that radiologic imaging was performed only if concerning signs or symptoms occurred.

The two groups had statistically indistinguishable overall survival, and in both groups, all patients experiencing relapse successfully achieved a second complete remission with salvage therapy.

In the routinely imaged group, scanning increased costs by nearly $20,000 per patient and by almost $600,000 per each relapse detected. In addition, patients were exposed to the associated radiation.

"We were unable to detect an overall survival benefit associated with routine surveillance imaging, although I have to acknowledge that our study was limited in power given the small number of deaths and relapses," commented Dr. Pingali, an oncologist with the Medical College of Wisconsin Affiliated Hospitals in Milwaukee.

"Relapses in both ... groups were effectively salvaged with autologous stem cell transplantation, arguing against a critical advantage of detection of asymptomatic relapse. Also, we need to keep in mind that the costs associated with routine surveillance imaging are significant, and it is also associated with potential risks, both in terms of radiation exposure and unnecessary work-up," he added.

"We do not feel that potential risks and costs without overall survival benefit or any other clinical benefit justify the practice of routine surveillance imaging in classical Hodgkin lymphoma patients who have achieved a complete remission after first-line therapy. We recommend that such patients be followed clinically," Dr. Pingali concluded.

Invited discussant Dr. Leo Gordon of Northwestern University in Chicago, agreed that accumulating data argue against routine imaging for surveillance in this context and noted that insurers will likely not continue to cover scans having no proven benefit. The data should prompt a revision of guidelines and reeducation of clinicians and patients, he said.

"For translational researchers and investigators and academics, I think we need to convince journal reviewers that a manuscript is acceptable if scans are not so frequent. And for industry trials, I think we need to discuss with the Food and Drug Administration the endpoint of progression-free survival and that those endpoints may not only be driven by scans but by more mundane parameters," he said—namely, the history and physical examination.

But session comoderator Dr. Gilles A. Salles of Hospices Civils de Lyon, Université Claude Bernard, France, expressed reservations, noting that the study did not provide information on how patients were allocated to groups and the time frame of relapse.

"It may be different whether relapses occur early, in the first year, or they occur later, and that may have some implications for the surveillance," he said. "I understand that you and many others jumped over the idea that we should immediately stop. A few people may think that we need more solid data, despite the provocative and quality data that were presented, to really make this jump in clinical practice. That’s my personal opinion."

Dr. Pingali and his team retrospectively reviewed the charts of adult patients who received a new diagnosis of classical Hodgkin lymphoma between 2000 and 2010 at three institutions, achieved complete remission after first-line therapy and had at least 2 years of follow-up.

The routine surveillance imaging and clinical surveillance groups had similar demographic and disease characteristics, Dr. Pingali reported. The former were significantly more likely to have received ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) and less likely to have received the Stanford V regimen as first-line therapy, and they were significantly less likely to have received radiation therapy.

With a median duration of follow-up of about 4 years, the groups did not differ significantly with respect to overall survival. "When we look at the 5-year time point, when typically the surveillance CT scans are discontinued, the curves are pretty much superimposable," he pointed out.

There were five deaths in the routine surveillance imaging group, one of which was from relapsed disease; the other deaths were from cancer, heart failure, hip fracture, and myelodysplastic syndrome. There were four deaths in the clinical surveillance group: two were from non-Hodgkin lymphoma and two from unknown causes while the patient was in confirmed remission.

All of the six patients in the routinely imaged group and all of the five patients in the clinically followed group experiencing a relapse achieved another complete remission with second-line therapy.

The mean number of scans received was 1.14 in the clinical surveillance group – usually the scan performed after first-line treatment to confirm remission, according to Dr. Pingali – and 4.25 in the routine surveillance imaging group. The ratio of scans to detected relapses was 18 vs. 124.

The extra charges incurred from scans using the routine surveillance imaging approach were $18,896/patient and $593,698/relapse.

"It is important to note that this does not include additional costs from the work-up of the false-positive scans and also the wages lost," he noted.

Dr. Pingali disclosed no relevant conflicts of interest. Dr. Gordon disclosed that he receives honoraria from Genentech and research funding from Millennium and Pharmacyclics. Dr. Salles disclosed serving as an advisor or consultant for Calistoga Pharmaceuticals, Celgene; Genentech, Janssen Pharmaceutica, and Roche. He has served as a speaker or a member of a speakers bureau and has received grants for clinical research from Celgene and Roche.