AMSTERDAM – Dr. Roy S. Herbst cites post hoc analysis of the FLEX trial as a highlight of IASLC's World Conference on Lung Cancer. Investigators quantified EGFR number by an immunohistochemistry stain. Tumors with high EGFR levels had a significantly better response to cetuximab than did tumors with low EGFR levels. His second highlight is a pilot study with five patients that used PET imaging and labeled erlotinib to noninvasively quantify EGFR expression in tumor cells, precluding the need for biopsied tissue.

AMSTERDAM – Dr. Roy S. Herbst cites post hoc analysis of the FLEX trial as a highlight of IASLC's World Conference on Lung Cancer. Investigators quantified EGFR number by an immunohistochemistry stain. Tumors with high EGFR levels had a significantly better response to cetuximab than did tumors with low EGFR levels. His second highlight is a pilot study with five patients that used PET imaging and labeled erlotinib to noninvasively quantify EGFR expression in tumor cells, precluding the need for biopsied tissue.

AMSTERDAM – Dr. Roy S. Herbst cites post hoc analysis of the FLEX trial as a highlight of IASLC's World Conference on Lung Cancer. Investigators quantified EGFR number by an immunohistochemistry stain. Tumors with high EGFR levels had a significantly better response to cetuximab than did tumors with low EGFR levels. His second highlight is a pilot study with five patients that used PET imaging and labeled erlotinib to noninvasively quantify EGFR expression in tumor cells, precluding the need for biopsied tissue.

LONDON – Close relatives of patients with acute myeloid leukemia and myelodysplastic syndromes can be reassured that they are not at increased risk of developing these diseases themselves, according to the findings of a large population-based registry trial.

"Among over 20,000 first-degree relatives of almost 7,000 AML [acute myeloid leukemia] patients, we found no excess risk of developing AML, MDS [myelodysplastic syndromes], or any myeloid neoplasms as a group," said Dr. Magnus Björkholm, a professor of medicine at Karolinska University Hospital, Solna and the Karolinska Institute, both in Stockholm.

Speaking at the annual congress of the European Hematology Association, Dr. Björkholm reported that there was also no strong genetic predisposition for first-degree relatives of patients with MDS to develop myeloid or other hematological neoplasms.

"If you read Wikipedia today, it says that the risk of developing AML is increased threefold in first-degree relatives of patients with AML," Dr. Björkholm observed. "But there is really limited data on the extent of familial aggregation of AML and MDS in the population.

Indeed, the Wikipedia entry cites a paper (J. Natl. Cancer Inst. 1969;42:517-24) from 1969 as the source of this claim, and results of early studies found an increased risk of leukemia among relatives of patients were actually accounted for by cases of chronic lymphocytic leukemia.

"We believe a better understanding on the role for genetic factors in the causation of AML/MDS is of major importance to patients, their families, and healthcare professionals," Dr. Björkholm said, explaining the rationale behind the research.

Using data from the Swedish Cancer Registry, the Swedish Population Registry, and the Swedish Multigenerational Registry, Dr. Björkholm and colleagues identified 6,962 patients diagnosed with AML from Jan. 1, 1958 until Dec. 31, 2004 and 1,388 MDS patients diagnosed from 1993 – the date when MDS was first included in the Swedish Cancer Registry – through Dec. 31, 2004. There were 20,579 first-degree relatives of the AML patients and 3,994 first-degree relatives of the MDS patients.

For each AML and MDS patient, four population-matched control subjects of a similar age, year of birth, and country of residence were randomly selected from the Swedish population, and their first-degree relatives were also identified. In all, there were 27,827 AML controls and 90,406 AML control relatives, and 5,312 MDS controls and 15,818 MDS control relatives.

No excess risk of AML (hazard ratio 0.94) or other myeloid or lymphoid malignancies was statistically significant in relatives of patients with AML with one exception – relatives of patients with AML did have an increased risk of polycythemia vera (HR 2.28, P less than .05). The risks for any hematopoietic or solid malignancies were significantly increased statistically, but only modestly, with risk ratios of 1.16 and 1.09, respectively.

First-degree relatives of AML patients who were diagnosed at a younger age (20 years or less) did, however, have a higher chance of developing AML, myeloid neoplasms, or multiple myeloma, based on small numbers in the sample. Dr. Björkholm suggested that genes predisposing to malignancy in general, environmental factors, or both, might be shared in these families.

No significant excess risks were seen among first-degree relatives of MDS patients.

"The lack of familial aggregation in AML and MDS is rather striking," Dr. Björkholm admitted. It is also "in stark contrast to findings in other myelo- and lymphoproliferative disorders."

In an interview, he emphasized, "The main message is that first-degree relatives of patients with acute myeloid leukemia do not have an increased risk of developing acute myeloid leukemia, which is in contrast to many other solid and hematological malignancies."

Dr. Björkholm also noted that patients are often told by their physicians that there is a two to three times increased risk of their siblings or children developing leukemia. The current findings suggest that this is unlikely, considering the large cohort of subjects that was studied.

"From a global point of view, this [study] is probably the best you can do."

Dr. Björkholm stated he had no conflicts of interest. The study received financial support from the Adolf H. Lundin Charitable Foundation, Karolinska Institute Foundations, Stockholm County Council, Swedish Cancer Society, and the Division of Intramural Research Programs at the National Cancer Institute of the National Institutes of Health.

LONDON – Close relatives of patients with acute myeloid leukemia and myelodysplastic syndromes can be reassured that they are not at increased risk of developing these diseases themselves, according to the findings of a large population-based registry trial.

"Among over 20,000 first-degree relatives of almost 7,000 AML [acute myeloid leukemia] patients, we found no excess risk of developing AML, MDS [myelodysplastic syndromes], or any myeloid neoplasms as a group," said Dr. Magnus Björkholm, a professor of medicine at Karolinska University Hospital, Solna and the Karolinska Institute, both in Stockholm.

Speaking at the annual congress of the European Hematology Association, Dr. Björkholm reported that there was also no strong genetic predisposition for first-degree relatives of patients with MDS to develop myeloid or other hematological neoplasms.

"If you read Wikipedia today, it says that the risk of developing AML is increased threefold in first-degree relatives of patients with AML," Dr. Björkholm observed. "But there is really limited data on the extent of familial aggregation of AML and MDS in the population.

Indeed, the Wikipedia entry cites a paper (J. Natl. Cancer Inst. 1969;42:517-24) from 1969 as the source of this claim, and results of early studies found an increased risk of leukemia among relatives of patients were actually accounted for by cases of chronic lymphocytic leukemia.

"We believe a better understanding on the role for genetic factors in the causation of AML/MDS is of major importance to patients, their families, and healthcare professionals," Dr. Björkholm said, explaining the rationale behind the research.

Using data from the Swedish Cancer Registry, the Swedish Population Registry, and the Swedish Multigenerational Registry, Dr. Björkholm and colleagues identified 6,962 patients diagnosed with AML from Jan. 1, 1958 until Dec. 31, 2004 and 1,388 MDS patients diagnosed from 1993 – the date when MDS was first included in the Swedish Cancer Registry – through Dec. 31, 2004. There were 20,579 first-degree relatives of the AML patients and 3,994 first-degree relatives of the MDS patients.

For each AML and MDS patient, four population-matched control subjects of a similar age, year of birth, and country of residence were randomly selected from the Swedish population, and their first-degree relatives were also identified. In all, there were 27,827 AML controls and 90,406 AML control relatives, and 5,312 MDS controls and 15,818 MDS control relatives.

No excess risk of AML (hazard ratio 0.94) or other myeloid or lymphoid malignancies was statistically significant in relatives of patients with AML with one exception – relatives of patients with AML did have an increased risk of polycythemia vera (HR 2.28, P less than .05). The risks for any hematopoietic or solid malignancies were significantly increased statistically, but only modestly, with risk ratios of 1.16 and 1.09, respectively.

First-degree relatives of AML patients who were diagnosed at a younger age (20 years or less) did, however, have a higher chance of developing AML, myeloid neoplasms, or multiple myeloma, based on small numbers in the sample. Dr. Björkholm suggested that genes predisposing to malignancy in general, environmental factors, or both, might be shared in these families.

No significant excess risks were seen among first-degree relatives of MDS patients.

"The lack of familial aggregation in AML and MDS is rather striking," Dr. Björkholm admitted. It is also "in stark contrast to findings in other myelo- and lymphoproliferative disorders."

In an interview, he emphasized, "The main message is that first-degree relatives of patients with acute myeloid leukemia do not have an increased risk of developing acute myeloid leukemia, which is in contrast to many other solid and hematological malignancies."

Dr. Björkholm also noted that patients are often told by their physicians that there is a two to three times increased risk of their siblings or children developing leukemia. The current findings suggest that this is unlikely, considering the large cohort of subjects that was studied.

"From a global point of view, this [study] is probably the best you can do."

Dr. Björkholm stated he had no conflicts of interest. The study received financial support from the Adolf H. Lundin Charitable Foundation, Karolinska Institute Foundations, Stockholm County Council, Swedish Cancer Society, and the Division of Intramural Research Programs at the National Cancer Institute of the National Institutes of Health.

LONDON – Close relatives of patients with acute myeloid leukemia and myelodysplastic syndromes can be reassured that they are not at increased risk of developing these diseases themselves, according to the findings of a large population-based registry trial.

"Among over 20,000 first-degree relatives of almost 7,000 AML [acute myeloid leukemia] patients, we found no excess risk of developing AML, MDS [myelodysplastic syndromes], or any myeloid neoplasms as a group," said Dr. Magnus Björkholm, a professor of medicine at Karolinska University Hospital, Solna and the Karolinska Institute, both in Stockholm.

Speaking at the annual congress of the European Hematology Association, Dr. Björkholm reported that there was also no strong genetic predisposition for first-degree relatives of patients with MDS to develop myeloid or other hematological neoplasms.

"If you read Wikipedia today, it says that the risk of developing AML is increased threefold in first-degree relatives of patients with AML," Dr. Björkholm observed. "But there is really limited data on the extent of familial aggregation of AML and MDS in the population.

Indeed, the Wikipedia entry cites a paper (J. Natl. Cancer Inst. 1969;42:517-24) from 1969 as the source of this claim, and results of early studies found an increased risk of leukemia among relatives of patients were actually accounted for by cases of chronic lymphocytic leukemia.

"We believe a better understanding on the role for genetic factors in the causation of AML/MDS is of major importance to patients, their families, and healthcare professionals," Dr. Björkholm said, explaining the rationale behind the research.

Using data from the Swedish Cancer Registry, the Swedish Population Registry, and the Swedish Multigenerational Registry, Dr. Björkholm and colleagues identified 6,962 patients diagnosed with AML from Jan. 1, 1958 until Dec. 31, 2004 and 1,388 MDS patients diagnosed from 1993 – the date when MDS was first included in the Swedish Cancer Registry – through Dec. 31, 2004. There were 20,579 first-degree relatives of the AML patients and 3,994 first-degree relatives of the MDS patients.

For each AML and MDS patient, four population-matched control subjects of a similar age, year of birth, and country of residence were randomly selected from the Swedish population, and their first-degree relatives were also identified. In all, there were 27,827 AML controls and 90,406 AML control relatives, and 5,312 MDS controls and 15,818 MDS control relatives.

No excess risk of AML (hazard ratio 0.94) or other myeloid or lymphoid malignancies was statistically significant in relatives of patients with AML with one exception – relatives of patients with AML did have an increased risk of polycythemia vera (HR 2.28, P less than .05). The risks for any hematopoietic or solid malignancies were significantly increased statistically, but only modestly, with risk ratios of 1.16 and 1.09, respectively.

First-degree relatives of AML patients who were diagnosed at a younger age (20 years or less) did, however, have a higher chance of developing AML, myeloid neoplasms, or multiple myeloma, based on small numbers in the sample. Dr. Björkholm suggested that genes predisposing to malignancy in general, environmental factors, or both, might be shared in these families.

No significant excess risks were seen among first-degree relatives of MDS patients.

"The lack of familial aggregation in AML and MDS is rather striking," Dr. Björkholm admitted. It is also "in stark contrast to findings in other myelo- and lymphoproliferative disorders."

In an interview, he emphasized, "The main message is that first-degree relatives of patients with acute myeloid leukemia do not have an increased risk of developing acute myeloid leukemia, which is in contrast to many other solid and hematological malignancies."

Dr. Björkholm also noted that patients are often told by their physicians that there is a two to three times increased risk of their siblings or children developing leukemia. The current findings suggest that this is unlikely, considering the large cohort of subjects that was studied.

"From a global point of view, this [study] is probably the best you can do."

Dr. Björkholm stated he had no conflicts of interest. The study received financial support from the Adolf H. Lundin Charitable Foundation, Karolinska Institute Foundations, Stockholm County Council, Swedish Cancer Society, and the Division of Intramural Research Programs at the National Cancer Institute of the National Institutes of Health.

LONDON – Measuring levels of a newly described protein at diagnosis could help identify patients that are going to fare worse than others with chronic myeloid leukemia, data from a small study suggest.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) levels were found to be significantly higher in patients with chronic myeloid leukemia (CML) who later went into blast crisis, reported researchers from the University of Liverpool (England). CIP2A could, therefore, represent a novel drug target as well as a biomarker for the disease.

"Prospective identification of patients whose CML will progress despite treatment is not currently possible and the work we have been doing is with PP2A, a tumor suppressor gene," explained Claire M. Lucas, a specialist health care scientist in the department of hematology at the university. Ms. Lucas presented the findings at the annual European Hematology Congress.

PP2A is a serine/threonine phosphatase that down-regulates cell-signaling pathways that lead to tumor cell proliferation, differentiation, and survival. The protein is key target of BCR-ABL1 signaling, and inhibition of the latter via imatinib (Gleevec) is known to increase levels of PP2A, to kick start apoptosis, and to suppress further tumor growth.

Ms. Lucas was part of a team led by Dr. Richard E. Clark that investigated whether the expression of PP2A or its inhibitory proteins SET and CIP2A differed in patients with CML before diagnosis and at disease progression.

The study included 31 patients with CML who were diagnosed in a chronic phase and who were being treated with imatinib within 4 weeks of their presentation. Patients were stratified into three groups based on their clinical response to treatment after 12 months: complete cytogenic response (CCR; n = 14), no CCR (n = 11), and blast crisis (n = 6).

Patients’ peripheral blood was collected before and after treatment for analysis, and evaluated according to their eventual clinical outcome. PP2A protein expression and phosphorylation were found to be increased in cells that had been taken from patients who were seen in blast crisis, Ms. Lucas reported.

CIP2A protein levels at diagnosis were also predictive of patients’ eventual outcome and were found to play a key role in regulating PP2A in CML cells. Chronic-phase patients who had high CIP2A levels at diagnosis had a 100% probability of progressing to blast crisis. Furthermore, CIPA siRNA was found to restore PP2A function and to decrease BCR-ABL tyrosine kinase activity.

Taken together, these data show that CIP2A is not only biologically but also clinically important in CML, Ms. Lucas said.

This is the first time an association between CIP2A and patient outcome has been shown in any hematologic malignancy, the research team believes. CIP2A levels have previously been linked to the aggressiveness of breast and gastric cancers (Clin. Cancer Res. 2009;15:5092-100; Clin. Cancer Res. 2008;14:3722-8; J. Natl. Cancer Inst. 2009;101:793-805).

The study findings have recently been published online (Blood 2011 April 13 [doi:10.1182/blood-2010-08-304477]). Ms. Lucas had no financial disclosures.

LONDON – Measuring levels of a newly described protein at diagnosis could help identify patients that are going to fare worse than others with chronic myeloid leukemia, data from a small study suggest.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) levels were found to be significantly higher in patients with chronic myeloid leukemia (CML) who later went into blast crisis, reported researchers from the University of Liverpool (England). CIP2A could, therefore, represent a novel drug target as well as a biomarker for the disease.

"Prospective identification of patients whose CML will progress despite treatment is not currently possible and the work we have been doing is with PP2A, a tumor suppressor gene," explained Claire M. Lucas, a specialist health care scientist in the department of hematology at the university. Ms. Lucas presented the findings at the annual European Hematology Congress.

PP2A is a serine/threonine phosphatase that down-regulates cell-signaling pathways that lead to tumor cell proliferation, differentiation, and survival. The protein is key target of BCR-ABL1 signaling, and inhibition of the latter via imatinib (Gleevec) is known to increase levels of PP2A, to kick start apoptosis, and to suppress further tumor growth.

Ms. Lucas was part of a team led by Dr. Richard E. Clark that investigated whether the expression of PP2A or its inhibitory proteins SET and CIP2A differed in patients with CML before diagnosis and at disease progression.

The study included 31 patients with CML who were diagnosed in a chronic phase and who were being treated with imatinib within 4 weeks of their presentation. Patients were stratified into three groups based on their clinical response to treatment after 12 months: complete cytogenic response (CCR; n = 14), no CCR (n = 11), and blast crisis (n = 6).

Patients’ peripheral blood was collected before and after treatment for analysis, and evaluated according to their eventual clinical outcome. PP2A protein expression and phosphorylation were found to be increased in cells that had been taken from patients who were seen in blast crisis, Ms. Lucas reported.

CIP2A protein levels at diagnosis were also predictive of patients’ eventual outcome and were found to play a key role in regulating PP2A in CML cells. Chronic-phase patients who had high CIP2A levels at diagnosis had a 100% probability of progressing to blast crisis. Furthermore, CIPA siRNA was found to restore PP2A function and to decrease BCR-ABL tyrosine kinase activity.

Taken together, these data show that CIP2A is not only biologically but also clinically important in CML, Ms. Lucas said.

This is the first time an association between CIP2A and patient outcome has been shown in any hematologic malignancy, the research team believes. CIP2A levels have previously been linked to the aggressiveness of breast and gastric cancers (Clin. Cancer Res. 2009;15:5092-100; Clin. Cancer Res. 2008;14:3722-8; J. Natl. Cancer Inst. 2009;101:793-805).

The study findings have recently been published online (Blood 2011 April 13 [doi:10.1182/blood-2010-08-304477]). Ms. Lucas had no financial disclosures.

LONDON – Measuring levels of a newly described protein at diagnosis could help identify patients that are going to fare worse than others with chronic myeloid leukemia, data from a small study suggest.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) levels were found to be significantly higher in patients with chronic myeloid leukemia (CML) who later went into blast crisis, reported researchers from the University of Liverpool (England). CIP2A could, therefore, represent a novel drug target as well as a biomarker for the disease.

"Prospective identification of patients whose CML will progress despite treatment is not currently possible and the work we have been doing is with PP2A, a tumor suppressor gene," explained Claire M. Lucas, a specialist health care scientist in the department of hematology at the university. Ms. Lucas presented the findings at the annual European Hematology Congress.

PP2A is a serine/threonine phosphatase that down-regulates cell-signaling pathways that lead to tumor cell proliferation, differentiation, and survival. The protein is key target of BCR-ABL1 signaling, and inhibition of the latter via imatinib (Gleevec) is known to increase levels of PP2A, to kick start apoptosis, and to suppress further tumor growth.

Ms. Lucas was part of a team led by Dr. Richard E. Clark that investigated whether the expression of PP2A or its inhibitory proteins SET and CIP2A differed in patients with CML before diagnosis and at disease progression.

The study included 31 patients with CML who were diagnosed in a chronic phase and who were being treated with imatinib within 4 weeks of their presentation. Patients were stratified into three groups based on their clinical response to treatment after 12 months: complete cytogenic response (CCR; n = 14), no CCR (n = 11), and blast crisis (n = 6).

Patients’ peripheral blood was collected before and after treatment for analysis, and evaluated according to their eventual clinical outcome. PP2A protein expression and phosphorylation were found to be increased in cells that had been taken from patients who were seen in blast crisis, Ms. Lucas reported.

CIP2A protein levels at diagnosis were also predictive of patients’ eventual outcome and were found to play a key role in regulating PP2A in CML cells. Chronic-phase patients who had high CIP2A levels at diagnosis had a 100% probability of progressing to blast crisis. Furthermore, CIPA siRNA was found to restore PP2A function and to decrease BCR-ABL tyrosine kinase activity.

Taken together, these data show that CIP2A is not only biologically but also clinically important in CML, Ms. Lucas said.

This is the first time an association between CIP2A and patient outcome has been shown in any hematologic malignancy, the research team believes. CIP2A levels have previously been linked to the aggressiveness of breast and gastric cancers (Clin. Cancer Res. 2009;15:5092-100; Clin. Cancer Res. 2008;14:3722-8; J. Natl. Cancer Inst. 2009;101:793-805).

The study findings have recently been published online (Blood 2011 April 13 [doi:10.1182/blood-2010-08-304477]). Ms. Lucas had no financial disclosures.

LONDON – The investigational agent brentuximab vedotin appears to have a beneficial effect in patients with refractory or relapsed Hodgkin’s lymphoma who are ineligible for or have refused to have an autologous stem cell transplant.

A retrospective analysis of two phase I studies performed with the drug used as a single agent have shown that almost one-third of these heavily pretreated patients are able to achieve an objective response to treatment.

Indeed, 6 of 20 patients (30%) aged a median of 32 years achieved an objective response (two complete and four partial remissions). The response can last longer than 6 months, with one patient achieving a durable remission for more than 2 years that later allowed for transplantation.

"These are very encouraging results in patients with [an] unmet need, and additional studies are ongoing," Dr. Ranjana Advani of Stanford University Medical Center in Palo Alto, Calif., said at the annual congress of the European Hematology Association.

"Patients who have primary refractory disease or fail to achieve a remission at relapse have a dismal outcome," Dr. Advani observed. She added that long-term survival prospects for such patients "were pretty bleak, with median overall survival in a small series as low as 4 months."

Brentuximab vedotin is a novel antibody-drug conjugate that comprises an anti-CD30 monoclonal antibody and a synthetic antimicrotubule agent, monomethyl auristatin E (MMAE). After binding to CD30 on the surface of T and B cells, the antibody-drug conjugate is internalized, the link between antibody and drug is severed, and MMAE is released – thus targeting malignant cells while, in theory, leaving normal cells unscathed.

MMAE is a potent antimicrotubule agent, and as with the taxanes, one of the expected side effects of the drug could be peripheral neuropathy. Although this was not seen in the small number of patients discussed by Dr. Advani, she said that peripheral neuropathy, mostly sensory, had been observed in about 15% of patients treated in the clinical trials program to date.

"Adverse events were seen in over 25% of patients, and these were not necessarily drug related; they could have been even disease related," Dr. Advani reported. Common side effects included fatigue (45%); nausea (40%); pyrexia (35%); decreased weight and diarrhea (30% each); vomiting, back pain, decreased appetite, anemia, and night sweats (25% each).

There were no deaths within 30 days of receiving the last dose of the novel agent.

The current findings add to data released separately from a pivotal phase II trial, recently updated and presented at this year’s American Society of Clinical Oncology meeting in Chicago. In that trial (J. Clin. Oncol. 2011 29[suppl.]: abstract 8031), brentuximab vedotin (SGN-35) induced objective responses in 75% of patients with relapsed or refractory Hodgkin’s disease; 34% achieved a durable complete remission, with two-thirds of patients remaining in complete remission.

Brentuximab has also recently been linked to durable remissions in patients with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL), an aggressive subtype of peripheral T-cell lymphoma.

The Food and Drug Administration has granted brentuximab vedotin orphan drug status for the treatment of Hodgkin’s lymphoma and sALCL.

Further studies are underway, and include the phase III AETHERA trial – which is comparing brentuximab vedotin to placebo in high-risk patients with Hodgkin’s lymphoma after autologous stem cell transplantation. Another phase I trial is also looking at the combination of brentuximab vedotin and the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen as de novo treatment in Hodgkin’s lymphoma.

Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.

LONDON – The investigational agent brentuximab vedotin appears to have a beneficial effect in patients with refractory or relapsed Hodgkin’s lymphoma who are ineligible for or have refused to have an autologous stem cell transplant.

A retrospective analysis of two phase I studies performed with the drug used as a single agent have shown that almost one-third of these heavily pretreated patients are able to achieve an objective response to treatment.

Indeed, 6 of 20 patients (30%) aged a median of 32 years achieved an objective response (two complete and four partial remissions). The response can last longer than 6 months, with one patient achieving a durable remission for more than 2 years that later allowed for transplantation.

"These are very encouraging results in patients with [an] unmet need, and additional studies are ongoing," Dr. Ranjana Advani of Stanford University Medical Center in Palo Alto, Calif., said at the annual congress of the European Hematology Association.

"Patients who have primary refractory disease or fail to achieve a remission at relapse have a dismal outcome," Dr. Advani observed. She added that long-term survival prospects for such patients "were pretty bleak, with median overall survival in a small series as low as 4 months."

Brentuximab vedotin is a novel antibody-drug conjugate that comprises an anti-CD30 monoclonal antibody and a synthetic antimicrotubule agent, monomethyl auristatin E (MMAE). After binding to CD30 on the surface of T and B cells, the antibody-drug conjugate is internalized, the link between antibody and drug is severed, and MMAE is released – thus targeting malignant cells while, in theory, leaving normal cells unscathed.

MMAE is a potent antimicrotubule agent, and as with the taxanes, one of the expected side effects of the drug could be peripheral neuropathy. Although this was not seen in the small number of patients discussed by Dr. Advani, she said that peripheral neuropathy, mostly sensory, had been observed in about 15% of patients treated in the clinical trials program to date.

"Adverse events were seen in over 25% of patients, and these were not necessarily drug related; they could have been even disease related," Dr. Advani reported. Common side effects included fatigue (45%); nausea (40%); pyrexia (35%); decreased weight and diarrhea (30% each); vomiting, back pain, decreased appetite, anemia, and night sweats (25% each).

There were no deaths within 30 days of receiving the last dose of the novel agent.

The current findings add to data released separately from a pivotal phase II trial, recently updated and presented at this year’s American Society of Clinical Oncology meeting in Chicago. In that trial (J. Clin. Oncol. 2011 29[suppl.]: abstract 8031), brentuximab vedotin (SGN-35) induced objective responses in 75% of patients with relapsed or refractory Hodgkin’s disease; 34% achieved a durable complete remission, with two-thirds of patients remaining in complete remission.

Brentuximab has also recently been linked to durable remissions in patients with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL), an aggressive subtype of peripheral T-cell lymphoma.

The Food and Drug Administration has granted brentuximab vedotin orphan drug status for the treatment of Hodgkin’s lymphoma and sALCL.

Further studies are underway, and include the phase III AETHERA trial – which is comparing brentuximab vedotin to placebo in high-risk patients with Hodgkin’s lymphoma after autologous stem cell transplantation. Another phase I trial is also looking at the combination of brentuximab vedotin and the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen as de novo treatment in Hodgkin’s lymphoma.

Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.

LONDON – The investigational agent brentuximab vedotin appears to have a beneficial effect in patients with refractory or relapsed Hodgkin’s lymphoma who are ineligible for or have refused to have an autologous stem cell transplant.

A retrospective analysis of two phase I studies performed with the drug used as a single agent have shown that almost one-third of these heavily pretreated patients are able to achieve an objective response to treatment.

Indeed, 6 of 20 patients (30%) aged a median of 32 years achieved an objective response (two complete and four partial remissions). The response can last longer than 6 months, with one patient achieving a durable remission for more than 2 years that later allowed for transplantation.

"These are very encouraging results in patients with [an] unmet need, and additional studies are ongoing," Dr. Ranjana Advani of Stanford University Medical Center in Palo Alto, Calif., said at the annual congress of the European Hematology Association.

"Patients who have primary refractory disease or fail to achieve a remission at relapse have a dismal outcome," Dr. Advani observed. She added that long-term survival prospects for such patients "were pretty bleak, with median overall survival in a small series as low as 4 months."

Brentuximab vedotin is a novel antibody-drug conjugate that comprises an anti-CD30 monoclonal antibody and a synthetic antimicrotubule agent, monomethyl auristatin E (MMAE). After binding to CD30 on the surface of T and B cells, the antibody-drug conjugate is internalized, the link between antibody and drug is severed, and MMAE is released – thus targeting malignant cells while, in theory, leaving normal cells unscathed.

MMAE is a potent antimicrotubule agent, and as with the taxanes, one of the expected side effects of the drug could be peripheral neuropathy. Although this was not seen in the small number of patients discussed by Dr. Advani, she said that peripheral neuropathy, mostly sensory, had been observed in about 15% of patients treated in the clinical trials program to date.

"Adverse events were seen in over 25% of patients, and these were not necessarily drug related; they could have been even disease related," Dr. Advani reported. Common side effects included fatigue (45%); nausea (40%); pyrexia (35%); decreased weight and diarrhea (30% each); vomiting, back pain, decreased appetite, anemia, and night sweats (25% each).

There were no deaths within 30 days of receiving the last dose of the novel agent.

The current findings add to data released separately from a pivotal phase II trial, recently updated and presented at this year’s American Society of Clinical Oncology meeting in Chicago. In that trial (J. Clin. Oncol. 2011 29[suppl.]: abstract 8031), brentuximab vedotin (SGN-35) induced objective responses in 75% of patients with relapsed or refractory Hodgkin’s disease; 34% achieved a durable complete remission, with two-thirds of patients remaining in complete remission.

Brentuximab has also recently been linked to durable remissions in patients with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL), an aggressive subtype of peripheral T-cell lymphoma.

The Food and Drug Administration has granted brentuximab vedotin orphan drug status for the treatment of Hodgkin’s lymphoma and sALCL.

Further studies are underway, and include the phase III AETHERA trial – which is comparing brentuximab vedotin to placebo in high-risk patients with Hodgkin’s lymphoma after autologous stem cell transplantation. Another phase I trial is also looking at the combination of brentuximab vedotin and the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen as de novo treatment in Hodgkin’s lymphoma.

Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.

LONDON – HIV-infected patients with Hodgkin’s lymphoma can be treated more or less the same as any other Hodgkin’s patient, according to new data from the German HIV-related Lymphoma Study Group.

In a prospective, multicenter study of 108 patients with Hodgkin’s lymphoma (HL), all of whom were HIV positive, a risk-adapted treatment strategy was found to be feasible while patients were being treated with HAART (highly active antiretroviral therapy).

"I think the main message is that the prognosis [of patients with HIV-related HL] has dramatically improved with the [use of] HAART and with the stage- and risk-adapted treatment approach," study investigator Dr. Marcus Hentrich said in a June 11 interview at the annual congress of the European Hematology Association, where he presented the study.

"The results are approaching those we have obtained in the HIV-negative population," added Dr. Hentrich of Harlaching Hospital Munich. The findings show that "not every patient needs to be treated with full intensity" for six to eight courses of chemotherapy; rather, "we can distinguish [treatment] depending on the Hodgkin’s stage."

HL is one of the most common non–AIDS-defining cancers that often presents at an advanced stage. To date, there have been few prospective studies looking at how best to treat patients who are both HIV positive and have the hematologic malignancy; indeed, patients with HIV-related HL are often excluded from HL clinical trials. As a consequence, how best to manage such patients remains unknown (Adv. Hematol. 2011 [doi:10.1155/2011/402682]).

Combination therapy regimens have largely been used to treat HL in HIV-infected patients because of the generally late presentation of the disease, and controlling HIV infection via HAART has also been shown to improve the outcome of HL (Ann. Oncol. 2006;17:914-9).

The current study presented by Dr. Hentrich was conducted between March 2004 and October 2010. It included 100 male and 8 female patients with HL who were HIV positive, and its aim was to see whether a risk-adapted treatment strategy that was used in HIV-negative patients with HL could be applied to those infected with HIV.

Treatment for HL was determined by the stage of disease, with two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) used with involved-field radiotherapy (30 Gy) in early-stage patients (that is, those with stage I-II HL and no additional risk factors).

In intermediate-stage patients (that is, those with stage I-II disease plus additional risk factors, such as large mediastinal tumor, extranodal involvement, and three or more lymph node regions involved), treatment consisted of four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus the same radiotherapy regimen.

More advanced HL (stage III-IV) was treated with six to eight cycles of BEACOPP plus facultative radiotherapy (30 Gy initial bulk or rest).

In patients with very advanced HIV infection and a poor performance status, the BEACOPP regimen could be replaced by ABVD, and the dose of ABVD reduced according to individual circumstances.

The median age of recruited patients was 43.9 years (range, 27-70 years). The majority (65%) had advanced disease, with 14% identified as having intermediate-stage HL, and 21% with early-stage disease. Extranodal involvement was observed in about half of patients (54%), and almost two-thirds (65%) had B-symptoms (which includes systemic symptoms such as fever, night sweats, and weight loss; B-symptoms can occur in both HL and non-HL).

Most (77%) patients had received HAART, and the median time from HIV to HL diagnosis was 5.9 years (range, 0-26 years).

After 26 months’ follow-up, 96%, 100%, and 84% of patients with early-, intermediate-, and advanced-stage HL, respectively, were in complete remission.

Perhaps not surprisingly, some advanced-stage patients fared worse, with four (6%) toxic and one (1.4%) unknown cause of death, five (7%) cases of early progression, and one (1.4%) partial remission in this group. One (4%) patient in the early-stage group also died because of toxicity.

Dr. Hentrich pointed out that treatment relapses and failures mainly occurred in patients with advanced disease.

Grade 3/4 toxicity was common and tended to occur in more patients who were treated with BEACOPP than AVBD, but the differences were statistically significantly only in the early-stage patients. The major hematologic toxicity was severe neutropenia.

At 2-years, progression-free and overall survival were 91.7% and 90.2%, respectively, for the whole population, and did not differ greatly between early-, intermediate-, and advanced-stage disease. However, patients with advanced disease and advanced HIV infection were more likely to have a reduced overall survival, compared with the other two groups of patients.

"The next strategy is to focus the amount of intensity to special patients, so we want to incorporate early PET scans after two cycles [of chemotherapy] and then de-escalate therapy or even escalate therapy," Dr. Hentrich said.

Dr. Hentrich had no financial disclosures or conflicts of interest.

LONDON – HIV-infected patients with Hodgkin’s lymphoma can be treated more or less the same as any other Hodgkin’s patient, according to new data from the German HIV-related Lymphoma Study Group.

In a prospective, multicenter study of 108 patients with Hodgkin’s lymphoma (HL), all of whom were HIV positive, a risk-adapted treatment strategy was found to be feasible while patients were being treated with HAART (highly active antiretroviral therapy).

"I think the main message is that the prognosis [of patients with HIV-related HL] has dramatically improved with the [use of] HAART and with the stage- and risk-adapted treatment approach," study investigator Dr. Marcus Hentrich said in a June 11 interview at the annual congress of the European Hematology Association, where he presented the study.

"The results are approaching those we have obtained in the HIV-negative population," added Dr. Hentrich of Harlaching Hospital Munich. The findings show that "not every patient needs to be treated with full intensity" for six to eight courses of chemotherapy; rather, "we can distinguish [treatment] depending on the Hodgkin’s stage."

HL is one of the most common non–AIDS-defining cancers that often presents at an advanced stage. To date, there have been few prospective studies looking at how best to treat patients who are both HIV positive and have the hematologic malignancy; indeed, patients with HIV-related HL are often excluded from HL clinical trials. As a consequence, how best to manage such patients remains unknown (Adv. Hematol. 2011 [doi:10.1155/2011/402682]).

Combination therapy regimens have largely been used to treat HL in HIV-infected patients because of the generally late presentation of the disease, and controlling HIV infection via HAART has also been shown to improve the outcome of HL (Ann. Oncol. 2006;17:914-9).

The current study presented by Dr. Hentrich was conducted between March 2004 and October 2010. It included 100 male and 8 female patients with HL who were HIV positive, and its aim was to see whether a risk-adapted treatment strategy that was used in HIV-negative patients with HL could be applied to those infected with HIV.

Treatment for HL was determined by the stage of disease, with two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) used with involved-field radiotherapy (30 Gy) in early-stage patients (that is, those with stage I-II HL and no additional risk factors).

In intermediate-stage patients (that is, those with stage I-II disease plus additional risk factors, such as large mediastinal tumor, extranodal involvement, and three or more lymph node regions involved), treatment consisted of four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus the same radiotherapy regimen.

More advanced HL (stage III-IV) was treated with six to eight cycles of BEACOPP plus facultative radiotherapy (30 Gy initial bulk or rest).

In patients with very advanced HIV infection and a poor performance status, the BEACOPP regimen could be replaced by ABVD, and the dose of ABVD reduced according to individual circumstances.

The median age of recruited patients was 43.9 years (range, 27-70 years). The majority (65%) had advanced disease, with 14% identified as having intermediate-stage HL, and 21% with early-stage disease. Extranodal involvement was observed in about half of patients (54%), and almost two-thirds (65%) had B-symptoms (which includes systemic symptoms such as fever, night sweats, and weight loss; B-symptoms can occur in both HL and non-HL).

Most (77%) patients had received HAART, and the median time from HIV to HL diagnosis was 5.9 years (range, 0-26 years).

After 26 months’ follow-up, 96%, 100%, and 84% of patients with early-, intermediate-, and advanced-stage HL, respectively, were in complete remission.

Perhaps not surprisingly, some advanced-stage patients fared worse, with four (6%) toxic and one (1.4%) unknown cause of death, five (7%) cases of early progression, and one (1.4%) partial remission in this group. One (4%) patient in the early-stage group also died because of toxicity.

Dr. Hentrich pointed out that treatment relapses and failures mainly occurred in patients with advanced disease.

Grade 3/4 toxicity was common and tended to occur in more patients who were treated with BEACOPP than AVBD, but the differences were statistically significantly only in the early-stage patients. The major hematologic toxicity was severe neutropenia.

At 2-years, progression-free and overall survival were 91.7% and 90.2%, respectively, for the whole population, and did not differ greatly between early-, intermediate-, and advanced-stage disease. However, patients with advanced disease and advanced HIV infection were more likely to have a reduced overall survival, compared with the other two groups of patients.

"The next strategy is to focus the amount of intensity to special patients, so we want to incorporate early PET scans after two cycles [of chemotherapy] and then de-escalate therapy or even escalate therapy," Dr. Hentrich said.

Dr. Hentrich had no financial disclosures or conflicts of interest.

LONDON – HIV-infected patients with Hodgkin’s lymphoma can be treated more or less the same as any other Hodgkin’s patient, according to new data from the German HIV-related Lymphoma Study Group.

In a prospective, multicenter study of 108 patients with Hodgkin’s lymphoma (HL), all of whom were HIV positive, a risk-adapted treatment strategy was found to be feasible while patients were being treated with HAART (highly active antiretroviral therapy).

"I think the main message is that the prognosis [of patients with HIV-related HL] has dramatically improved with the [use of] HAART and with the stage- and risk-adapted treatment approach," study investigator Dr. Marcus Hentrich said in a June 11 interview at the annual congress of the European Hematology Association, where he presented the study.

"The results are approaching those we have obtained in the HIV-negative population," added Dr. Hentrich of Harlaching Hospital Munich. The findings show that "not every patient needs to be treated with full intensity" for six to eight courses of chemotherapy; rather, "we can distinguish [treatment] depending on the Hodgkin’s stage."

HL is one of the most common non–AIDS-defining cancers that often presents at an advanced stage. To date, there have been few prospective studies looking at how best to treat patients who are both HIV positive and have the hematologic malignancy; indeed, patients with HIV-related HL are often excluded from HL clinical trials. As a consequence, how best to manage such patients remains unknown (Adv. Hematol. 2011 [doi:10.1155/2011/402682]).

Combination therapy regimens have largely been used to treat HL in HIV-infected patients because of the generally late presentation of the disease, and controlling HIV infection via HAART has also been shown to improve the outcome of HL (Ann. Oncol. 2006;17:914-9).

The current study presented by Dr. Hentrich was conducted between March 2004 and October 2010. It included 100 male and 8 female patients with HL who were HIV positive, and its aim was to see whether a risk-adapted treatment strategy that was used in HIV-negative patients with HL could be applied to those infected with HIV.

Treatment for HL was determined by the stage of disease, with two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) used with involved-field radiotherapy (30 Gy) in early-stage patients (that is, those with stage I-II HL and no additional risk factors).

In intermediate-stage patients (that is, those with stage I-II disease plus additional risk factors, such as large mediastinal tumor, extranodal involvement, and three or more lymph node regions involved), treatment consisted of four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus the same radiotherapy regimen.

More advanced HL (stage III-IV) was treated with six to eight cycles of BEACOPP plus facultative radiotherapy (30 Gy initial bulk or rest).

In patients with very advanced HIV infection and a poor performance status, the BEACOPP regimen could be replaced by ABVD, and the dose of ABVD reduced according to individual circumstances.

The median age of recruited patients was 43.9 years (range, 27-70 years). The majority (65%) had advanced disease, with 14% identified as having intermediate-stage HL, and 21% with early-stage disease. Extranodal involvement was observed in about half of patients (54%), and almost two-thirds (65%) had B-symptoms (which includes systemic symptoms such as fever, night sweats, and weight loss; B-symptoms can occur in both HL and non-HL).

Most (77%) patients had received HAART, and the median time from HIV to HL diagnosis was 5.9 years (range, 0-26 years).

After 26 months’ follow-up, 96%, 100%, and 84% of patients with early-, intermediate-, and advanced-stage HL, respectively, were in complete remission.

Perhaps not surprisingly, some advanced-stage patients fared worse, with four (6%) toxic and one (1.4%) unknown cause of death, five (7%) cases of early progression, and one (1.4%) partial remission in this group. One (4%) patient in the early-stage group also died because of toxicity.

Dr. Hentrich pointed out that treatment relapses and failures mainly occurred in patients with advanced disease.

Grade 3/4 toxicity was common and tended to occur in more patients who were treated with BEACOPP than AVBD, but the differences were statistically significantly only in the early-stage patients. The major hematologic toxicity was severe neutropenia.

At 2-years, progression-free and overall survival were 91.7% and 90.2%, respectively, for the whole population, and did not differ greatly between early-, intermediate-, and advanced-stage disease. However, patients with advanced disease and advanced HIV infection were more likely to have a reduced overall survival, compared with the other two groups of patients.

"The next strategy is to focus the amount of intensity to special patients, so we want to incorporate early PET scans after two cycles [of chemotherapy] and then de-escalate therapy or even escalate therapy," Dr. Hentrich said.

Dr. Hentrich had no financial disclosures or conflicts of interest.

LONDON – Stopping treatment with dasatinib and nilotinib might be safe in chronic myeloid leukemia patients who have achieved sustained and complete molecular responses, early data from a pilot study have shown.

The STOP 2GTKI study is a successor to the STop IMatinib (STIM) trial, which showed that stopping treatment with imatinib – the first-generation tyrosine kinase inhibitor (TKI) of BCR-ABL – could be feasible in patients who achieve long-lasting complete molecular responses (Lancet Oncol.2010;11:1029-35).

Although still preliminary, the new data suggest that it could be possible to do the same with these second-generation TKIs in patients who were previously intolerant or resistant to treatment with imatinib, Dr. Delphine Réa said at the annual Congress of the European Hematology Association.

"There are different kinds of reasons why we should aim at stopping tyrosine kinase inhibitors in chronic myeloid leukemia patients," said Dr. Réa of Hôpital Saint-Louis in Paris.

"The first one relates to patients. From the patients’ perspective it’s very important to have the hope of feeling cured," said Dr. Réa, a member of the French team that performed both the STIM and the STOP 2G-TKI studies.

Other reasons given include avoiding the adverse effects of prolonged therapy on quality of life, and reducing health care costs by steering clear of unnecessary long-term treatment for what becomes a chronic disease. It’s also important for clinicians to be able to show that a treatment really does cure a disease, she said, and the only way to do that is to stop the treatment.

Dr. Réa presented early data on 14 patients who had been enrolled in the STOP 2G-TKI pilot study until May 2011 and for whom there was at least 6 months’ follow-up. The median age of patients was 59 years.

"I think it’s very important to have 6 months’ follow-up at least because in the STop IMatinib trial, most of the relapses occurred within the first 6 months," Dr. Réa explained in an interview after her presentation.

"Here we didn’t have any relapses after 6 months," Dr. Réa added. "For the nine patients who didn’t relapse, the median follow-up is 10 months." The duration of time that these patients remained treatment free was between 6 months and 19 months.

For inclusion in the study, patients had to be aged 18 years or older with chronic or acute phase chronic myeloid leukemia at diagnosis, and be receiving ongoing dasatinib or nilotinib treatment after intolerance or resistance to imatinib therapy. TKI treatment had to have been administered for at least 3 years, and patients needed to have undetectable levels of BCR-ABL with at least 20,000 copies of ABL.

The primary end point was the achievement of a stable major molecular response (MMR) at 6 months, determined by monthly blood counts and real-time quantitative polymerase chain reaction for the first year of discontinuation, then every 2-3 months thereafter. Bone marrow smears and cytogenic and mutational analysis are undertaken if there is a rise in BCR-ABL above an internationally standardized (IS) ratio of 1%. Patients are re-treated with dasatinib or nilotinib if there is a loss of MMR of more than 0.1% IS.

Results showed that at 6 months’ follow-up, 71% of patients had a persistent MMR, and 64% remained treatment free. Five patients restarted TKI treatment at a median of 5 months, and four patients lost MMR after a median of 3 months. However, the patients who lost major molecular response retained their sensitivity to TKIs, and BCR-ABL was undetectable in all five patients who restarted therapy.

Asked what these results could mean for clinical practice, Dr. Réa noted that they are an early indicator that stopping treatment with second-generation TKIs will probably be an option for some patients who achieve good responses. Careful (at least monthly) follow-up of patients who cease treatment would be required, at least in the research setting.

"We don’t know, but we hope the relapse rate will be lower than we have seen with imatinib [discontinuation]," Dr. Réa said. She added, however, that there is an indication that the relapse rate could actually be higher than that seen in the STIM trial.

As yet, the optimal duration of treatment with a second-generation TKI before discontinuation can be attempted is unknown. "In the STop IMatinib trial, it seems to be between 4 and 5 years," Dr. Réa observed. "So I don’t think it will be reasonable to stop treatment before that period of time."

Further results from the trial can be expected later in the year, Dr. Réa noted. To date, 23 patients have been recruited and 8 more are to be included in the trial.

Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.

LONDON – Stopping treatment with dasatinib and nilotinib might be safe in chronic myeloid leukemia patients who have achieved sustained and complete molecular responses, early data from a pilot study have shown.

The STOP 2GTKI study is a successor to the STop IMatinib (STIM) trial, which showed that stopping treatment with imatinib – the first-generation tyrosine kinase inhibitor (TKI) of BCR-ABL – could be feasible in patients who achieve long-lasting complete molecular responses (Lancet Oncol.2010;11:1029-35).

Although still preliminary, the new data suggest that it could be possible to do the same with these second-generation TKIs in patients who were previously intolerant or resistant to treatment with imatinib, Dr. Delphine Réa said at the annual Congress of the European Hematology Association.

"There are different kinds of reasons why we should aim at stopping tyrosine kinase inhibitors in chronic myeloid leukemia patients," said Dr. Réa of Hôpital Saint-Louis in Paris.

"The first one relates to patients. From the patients’ perspective it’s very important to have the hope of feeling cured," said Dr. Réa, a member of the French team that performed both the STIM and the STOP 2G-TKI studies.

Other reasons given include avoiding the adverse effects of prolonged therapy on quality of life, and reducing health care costs by steering clear of unnecessary long-term treatment for what becomes a chronic disease. It’s also important for clinicians to be able to show that a treatment really does cure a disease, she said, and the only way to do that is to stop the treatment.

Dr. Réa presented early data on 14 patients who had been enrolled in the STOP 2G-TKI pilot study until May 2011 and for whom there was at least 6 months’ follow-up. The median age of patients was 59 years.

"I think it’s very important to have 6 months’ follow-up at least because in the STop IMatinib trial, most of the relapses occurred within the first 6 months," Dr. Réa explained in an interview after her presentation.

"Here we didn’t have any relapses after 6 months," Dr. Réa added. "For the nine patients who didn’t relapse, the median follow-up is 10 months." The duration of time that these patients remained treatment free was between 6 months and 19 months.

For inclusion in the study, patients had to be aged 18 years or older with chronic or acute phase chronic myeloid leukemia at diagnosis, and be receiving ongoing dasatinib or nilotinib treatment after intolerance or resistance to imatinib therapy. TKI treatment had to have been administered for at least 3 years, and patients needed to have undetectable levels of BCR-ABL with at least 20,000 copies of ABL.

The primary end point was the achievement of a stable major molecular response (MMR) at 6 months, determined by monthly blood counts and real-time quantitative polymerase chain reaction for the first year of discontinuation, then every 2-3 months thereafter. Bone marrow smears and cytogenic and mutational analysis are undertaken if there is a rise in BCR-ABL above an internationally standardized (IS) ratio of 1%. Patients are re-treated with dasatinib or nilotinib if there is a loss of MMR of more than 0.1% IS.

Results showed that at 6 months’ follow-up, 71% of patients had a persistent MMR, and 64% remained treatment free. Five patients restarted TKI treatment at a median of 5 months, and four patients lost MMR after a median of 3 months. However, the patients who lost major molecular response retained their sensitivity to TKIs, and BCR-ABL was undetectable in all five patients who restarted therapy.

Asked what these results could mean for clinical practice, Dr. Réa noted that they are an early indicator that stopping treatment with second-generation TKIs will probably be an option for some patients who achieve good responses. Careful (at least monthly) follow-up of patients who cease treatment would be required, at least in the research setting.

"We don’t know, but we hope the relapse rate will be lower than we have seen with imatinib [discontinuation]," Dr. Réa said. She added, however, that there is an indication that the relapse rate could actually be higher than that seen in the STIM trial.

As yet, the optimal duration of treatment with a second-generation TKI before discontinuation can be attempted is unknown. "In the STop IMatinib trial, it seems to be between 4 and 5 years," Dr. Réa observed. "So I don’t think it will be reasonable to stop treatment before that period of time."

Further results from the trial can be expected later in the year, Dr. Réa noted. To date, 23 patients have been recruited and 8 more are to be included in the trial.

Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.

LONDON – Stopping treatment with dasatinib and nilotinib might be safe in chronic myeloid leukemia patients who have achieved sustained and complete molecular responses, early data from a pilot study have shown.

The STOP 2GTKI study is a successor to the STop IMatinib (STIM) trial, which showed that stopping treatment with imatinib – the first-generation tyrosine kinase inhibitor (TKI) of BCR-ABL – could be feasible in patients who achieve long-lasting complete molecular responses (Lancet Oncol.2010;11:1029-35).

Although still preliminary, the new data suggest that it could be possible to do the same with these second-generation TKIs in patients who were previously intolerant or resistant to treatment with imatinib, Dr. Delphine Réa said at the annual Congress of the European Hematology Association.

"There are different kinds of reasons why we should aim at stopping tyrosine kinase inhibitors in chronic myeloid leukemia patients," said Dr. Réa of Hôpital Saint-Louis in Paris.

"The first one relates to patients. From the patients’ perspective it’s very important to have the hope of feeling cured," said Dr. Réa, a member of the French team that performed both the STIM and the STOP 2G-TKI studies.

Other reasons given include avoiding the adverse effects of prolonged therapy on quality of life, and reducing health care costs by steering clear of unnecessary long-term treatment for what becomes a chronic disease. It’s also important for clinicians to be able to show that a treatment really does cure a disease, she said, and the only way to do that is to stop the treatment.

Dr. Réa presented early data on 14 patients who had been enrolled in the STOP 2G-TKI pilot study until May 2011 and for whom there was at least 6 months’ follow-up. The median age of patients was 59 years.

"I think it’s very important to have 6 months’ follow-up at least because in the STop IMatinib trial, most of the relapses occurred within the first 6 months," Dr. Réa explained in an interview after her presentation.

"Here we didn’t have any relapses after 6 months," Dr. Réa added. "For the nine patients who didn’t relapse, the median follow-up is 10 months." The duration of time that these patients remained treatment free was between 6 months and 19 months.

For inclusion in the study, patients had to be aged 18 years or older with chronic or acute phase chronic myeloid leukemia at diagnosis, and be receiving ongoing dasatinib or nilotinib treatment after intolerance or resistance to imatinib therapy. TKI treatment had to have been administered for at least 3 years, and patients needed to have undetectable levels of BCR-ABL with at least 20,000 copies of ABL.

The primary end point was the achievement of a stable major molecular response (MMR) at 6 months, determined by monthly blood counts and real-time quantitative polymerase chain reaction for the first year of discontinuation, then every 2-3 months thereafter. Bone marrow smears and cytogenic and mutational analysis are undertaken if there is a rise in BCR-ABL above an internationally standardized (IS) ratio of 1%. Patients are re-treated with dasatinib or nilotinib if there is a loss of MMR of more than 0.1% IS.

Results showed that at 6 months’ follow-up, 71% of patients had a persistent MMR, and 64% remained treatment free. Five patients restarted TKI treatment at a median of 5 months, and four patients lost MMR after a median of 3 months. However, the patients who lost major molecular response retained their sensitivity to TKIs, and BCR-ABL was undetectable in all five patients who restarted therapy.

Asked what these results could mean for clinical practice, Dr. Réa noted that they are an early indicator that stopping treatment with second-generation TKIs will probably be an option for some patients who achieve good responses. Careful (at least monthly) follow-up of patients who cease treatment would be required, at least in the research setting.

"We don’t know, but we hope the relapse rate will be lower than we have seen with imatinib [discontinuation]," Dr. Réa said. She added, however, that there is an indication that the relapse rate could actually be higher than that seen in the STIM trial.

As yet, the optimal duration of treatment with a second-generation TKI before discontinuation can be attempted is unknown. "In the STop IMatinib trial, it seems to be between 4 and 5 years," Dr. Réa observed. "So I don’t think it will be reasonable to stop treatment before that period of time."

Further results from the trial can be expected later in the year, Dr. Réa noted. To date, 23 patients have been recruited and 8 more are to be included in the trial.

Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

AMSTERDAM – The International Association for the Study of Lung Cancer has issued a call for physicians to discuss lung cancer screening with patients who match the high-risk smoking history of the people enrolled in the landmark National Lung Screening Trial.

The National Lung Screening Trial (NLST) showed that an annual, low-dose CT chest scan can lead to significant reductions in lung cancer deaths and overall mortality in patients aged 55-74 years who smoked for at least 30 pack-years and, if former smokers, quit within the prior 15 years (New Engl. J. Med. 2011 [doi: 364:10.1056/NEJMoa1102873).

Based on these unprecedented findings, the International Association for the Study of Lung Cancer (IASLC)’s position-writing committee issued a call for physicians to discuss the data and its implications with such patients.

"It is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening," said the statement, issued as IASLC started its world conference

Although some committee members, including the chairman, urged caution when routinely discussing screening with the target population before the cost effectiveness of this approach is proven, two of the Americans on the 10-member position-statement writing committee endorsed immediately offering screening to fully informed people who match the study’s screening profile.

"For patients with metastatic lung cancer the cure rate is essentially zero. Finding lung cancer early is the best way to deal with this disease, and that’s why this is such an extraordinary result," said Dr. Roy S. Herbst, a member of the task force and chief of medical oncology at Yale University in New Haven, Conn.

"Even with all the cautions, I think that in the United States at least you’ll see screening, especially since the NLST was largely sponsored by the National Cancer Institute. Assuming that the CMS [Centers for Medicare and Medicaid Services] and insurers will pick this up, I think [screening] is something we’re going to see. I think there will be great pressure in the United States for this to be covered, at a cost of about $300-$400 per scan.

"At Yale, we’ll start screening people who meet the enrollment criteria for the trial, as will several other U.S. centers. We’ll offer screening with all the caveats," including informing patients about the risks they will face from screening, their need to stop smoking, their need for ongoing screening, and the need to have a multidisciplinary team in place at the screening site to deal with all the possible consequences of screening, Dr. Herbst said.

"We know there is effectiveness from screening, but is there cost effectiveness? Is there value?" asked Dr. Richard Gralla, another member of the statement-writing committee and chief of hematology-oncology at North Shore University Medical Center and Long Island Jewish Medical Center in New Hyde Park, N.Y.

"My prediction is that screening will not only be shown to be cost effective, but it will be very cost effective. It will also be very expensive" to run annual screens on the millions of middle-aged smokers who meet the trial’s screening profile, he added. The NLST report estimated that 7 million Americans match the age and smoking history of the people enrolled in the trial.

By thrusting medicine into a new era of routine lung cancer screening, these developments will trigger creation of a new system of quality oversight for lung cancer screening that will likely follow the model of breast cancer screening.

"There is a laundry list of requirements that will need to be established by the institutions that want to do CT screening," said Dr. Denise R. Aberle, professor of radiology at the University of California, Los Angeles, and a collaborator on the NLST. "That will likely evolve into a form of accreditation to better guarantee quality assurance, as with breast cancer screening." Dr. Aberle also noted that the NLST researchers collected cost-effectiveness data, and that they will soon release a report on their analysis of those data.

Routine lung cancer screening will also place new responsibilities on the thoracic surgeons who follow up on suspicious lung lesions found though screening, most of which will not be cancers.

"For surgeons it will be a very large challenge to offer correct treatment to patients with very small cancers," said Dr. Jesper Pedersen, a thoracic surgeon at Copenhagen University Hospital. "We’re planning on writing guidelines for surgeons, because they will be at risk by operating on so many patients without lung cancer." The NLST results showed that 96% of suspicious lesions identified by CT screening were not cancers.

"There is potential for physical and psychiatric harm from cancer screening, but the results from many studies of breast cancer screening have shown that the benefits of screening outweigh its harms," said IASLC president David R. Gandara, professor of medicine and director of the thoracic oncology program at the University of California, Davis, in Sacramento.

"We’re in the early days of screening for lung cancer, and we must do everything to make sure that screening is done appropriately and that follow-up is appropriate. But our message to patients about screening is positive. We can’t overemphasize that," Dr. Gandara said.

Dr. Herbst said that he has been a consultant to Genentech, Agennix, Allos Therapeutics, Boehringer Ingelheim, and OSI Pharmaceuticals. He has been on the advisory boards of Amgen, Biothera, Genetics Squared (now Everist Genomics), MedTrust, N-of-One, SunDev, Targeted Molecular Diagnostics, and DiaTech. He has received research grants from Genentech, Amgen, Bristol-Myers Squibb, AstraZeneca, Novartis, OSI, Oncothyreon, Geron, Sanofi-Aventis, Pfizer, and ImClone.

Dr. Gralla and Dr. Aberle had no relevant disclosures. Dr. Pedersen said that he has been on the speakers bureau for Eli Lilly and Roche and received grant support from AstraZeneca. Dr. Gandara said that he has been a consultant to Amgen, AstraZeneca, Biodesix, Bristol-Myers Squibb/ImClone, GlaxoSmithKline, Genentech, Merck, Novartis, Sanofi-Aventis, and Response Genetics; he has received research support from Abbott, Bristol-Myers Squibb/ImClone, Genentech, Lilly, Merck, Novartis, and Pfizer.

A new study that links intensive-dose statin therapy to increased risk of developing diabetes mellitus is unlikely to convince HM or any other specialty to discontinue the treatment, a hospitalist focused on glycemic issues says.

A recent JAMA article reports that a meta-analysis of five clinical trials showed intensive statin regimen was associated with a 12% increased diabetes incidence over moderate-dose regimens (JAMA. 2011;305(24):2556-2564). The authors found that it would take 498 patients taking a statin to cause one extra case of diabetes. Conversely, only 155 people taking a statin would prevent one heart attack.

“The benefits of statins are just too well documented to ignore,” says Steven C. Smith, MD, FHM, medical director of hospitalist services at Healthcare Authority for Medical West in Bessemer, Ala. Quoting a cardiologist colleague, he adds, “statins are so beneficial, there is no way I wouldn’t use them because of a higher risk for diabetes.”

Dr. Smith, who leads the SHM-sponsored Glycemic Control Mentored Implementation program at his hospital, says the research is a formal link for what many hospitalists already realize: patients taking statins because of cardiovascular risk factors usually are at risk for diabetes. He adds that “modifiable risk factors”—including sedentary lifestyle, weight issues and diet—are prevalent in both patient groups. He refers to the JAMA research as “the last stone on the scale that tips the scale.”

“You have to weigh one versus the other,” Dr. Smith says. “The population of people on statins are already at risk for diabetes...you really have to address the risk factors that will solve both problems.”

A new study that links intensive-dose statin therapy to increased risk of developing diabetes mellitus is unlikely to convince HM or any other specialty to discontinue the treatment, a hospitalist focused on glycemic issues says.

A recent JAMA article reports that a meta-analysis of five clinical trials showed intensive statin regimen was associated with a 12% increased diabetes incidence over moderate-dose regimens (JAMA. 2011;305(24):2556-2564). The authors found that it would take 498 patients taking a statin to cause one extra case of diabetes. Conversely, only 155 people taking a statin would prevent one heart attack.

“The benefits of statins are just too well documented to ignore,” says Steven C. Smith, MD, FHM, medical director of hospitalist services at Healthcare Authority for Medical West in Bessemer, Ala. Quoting a cardiologist colleague, he adds, “statins are so beneficial, there is no way I wouldn’t use them because of a higher risk for diabetes.”

Dr. Smith, who leads the SHM-sponsored Glycemic Control Mentored Implementation program at his hospital, says the research is a formal link for what many hospitalists already realize: patients taking statins because of cardiovascular risk factors usually are at risk for diabetes. He adds that “modifiable risk factors”—including sedentary lifestyle, weight issues and diet—are prevalent in both patient groups. He refers to the JAMA research as “the last stone on the scale that tips the scale.”

“You have to weigh one versus the other,” Dr. Smith says. “The population of people on statins are already at risk for diabetes...you really have to address the risk factors that will solve both problems.”

A new study that links intensive-dose statin therapy to increased risk of developing diabetes mellitus is unlikely to convince HM or any other specialty to discontinue the treatment, a hospitalist focused on glycemic issues says.

A recent JAMA article reports that a meta-analysis of five clinical trials showed intensive statin regimen was associated with a 12% increased diabetes incidence over moderate-dose regimens (JAMA. 2011;305(24):2556-2564). The authors found that it would take 498 patients taking a statin to cause one extra case of diabetes. Conversely, only 155 people taking a statin would prevent one heart attack.

“The benefits of statins are just too well documented to ignore,” says Steven C. Smith, MD, FHM, medical director of hospitalist services at Healthcare Authority for Medical West in Bessemer, Ala. Quoting a cardiologist colleague, he adds, “statins are so beneficial, there is no way I wouldn’t use them because of a higher risk for diabetes.”

Dr. Smith, who leads the SHM-sponsored Glycemic Control Mentored Implementation program at his hospital, says the research is a formal link for what many hospitalists already realize: patients taking statins because of cardiovascular risk factors usually are at risk for diabetes. He adds that “modifiable risk factors”—including sedentary lifestyle, weight issues and diet—are prevalent in both patient groups. He refers to the JAMA research as “the last stone on the scale that tips the scale.”

“You have to weigh one versus the other,” Dr. Smith says. “The population of people on statins are already at risk for diabetes...you really have to address the risk factors that will solve both problems.”

Every May, Mayo Clinic hospitalist Jason Persoff, MD, SFHM, sheds his doctor’s gear, grabs his camera and camcorder, and heads to the Midwest in search of ferocious weather for two weeks. This year, the Jacksonville, Fla.-based physician put his doctor’s gear back on sooner than he expected.

After 20 years of chasing storms, he found himself in what might have been considered a situation that was inevitable: helping people injured in a tornado. When a monstrous twister barreled through Joplin, Mo., last month, Dr. Persoff was less than a mile from its path. He and his “chase partner,” Robert Balogh, MD, an Oklahoma-based internist and former hospitalist, were able to rush in and assist in the aftermath.

One hospital serving the area, St. John’s Regional Medical Center, was destroyed, its roof ripped off by 200 mph winds.

Dr. Persoff checked in at the emergency room of the other one, Freeman Health System, and offered his help. He spent 10 hours there—first treating trauma patients.

“The initial trauma that came in was pretty fast and furious,” he says. “If somebody could be saved, and it wasn’t going to require an effort that would jeopardize resources, they did everything they could to save people.”

There were amputations, impalements, eviscerations. Some patients were covered in glass, he recalls. When the patients from St. John’s began to arrive at Freeman, Dr. Persoff treated them, doing admission orders on 24 patients.

Dr. Persoff plans to continue storm-chasing next year. But he says he’ll never forget the trauma nurse who was working as he arrived at Freeman and was still working as he left the hospital.

“That was one of the times where I was like, ‘Wow, this is really humbling,’ ” he says.

Check out photos and journal entries of Dr. Persoff’s storm-chasing adventures at http://stormdoctor.com/.

Every May, Mayo Clinic hospitalist Jason Persoff, MD, SFHM, sheds his doctor’s gear, grabs his camera and camcorder, and heads to the Midwest in search of ferocious weather for two weeks. This year, the Jacksonville, Fla.-based physician put his doctor’s gear back on sooner than he expected.

After 20 years of chasing storms, he found himself in what might have been considered a situation that was inevitable: helping people injured in a tornado. When a monstrous twister barreled through Joplin, Mo., last month, Dr. Persoff was less than a mile from its path. He and his “chase partner,” Robert Balogh, MD, an Oklahoma-based internist and former hospitalist, were able to rush in and assist in the aftermath.

One hospital serving the area, St. John’s Regional Medical Center, was destroyed, its roof ripped off by 200 mph winds.

Dr. Persoff checked in at the emergency room of the other one, Freeman Health System, and offered his help. He spent 10 hours there—first treating trauma patients.

“The initial trauma that came in was pretty fast and furious,” he says. “If somebody could be saved, and it wasn’t going to require an effort that would jeopardize resources, they did everything they could to save people.”

There were amputations, impalements, eviscerations. Some patients were covered in glass, he recalls. When the patients from St. John’s began to arrive at Freeman, Dr. Persoff treated them, doing admission orders on 24 patients.

Dr. Persoff plans to continue storm-chasing next year. But he says he’ll never forget the trauma nurse who was working as he arrived at Freeman and was still working as he left the hospital.

“That was one of the times where I was like, ‘Wow, this is really humbling,’ ” he says.

Check out photos and journal entries of Dr. Persoff’s storm-chasing adventures at http://stormdoctor.com/.

Every May, Mayo Clinic hospitalist Jason Persoff, MD, SFHM, sheds his doctor’s gear, grabs his camera and camcorder, and heads to the Midwest in search of ferocious weather for two weeks. This year, the Jacksonville, Fla.-based physician put his doctor’s gear back on sooner than he expected.

After 20 years of chasing storms, he found himself in what might have been considered a situation that was inevitable: helping people injured in a tornado. When a monstrous twister barreled through Joplin, Mo., last month, Dr. Persoff was less than a mile from its path. He and his “chase partner,” Robert Balogh, MD, an Oklahoma-based internist and former hospitalist, were able to rush in and assist in the aftermath.

One hospital serving the area, St. John’s Regional Medical Center, was destroyed, its roof ripped off by 200 mph winds.

Dr. Persoff checked in at the emergency room of the other one, Freeman Health System, and offered his help. He spent 10 hours there—first treating trauma patients.

“The initial trauma that came in was pretty fast and furious,” he says. “If somebody could be saved, and it wasn’t going to require an effort that would jeopardize resources, they did everything they could to save people.”

There were amputations, impalements, eviscerations. Some patients were covered in glass, he recalls. When the patients from St. John’s began to arrive at Freeman, Dr. Persoff treated them, doing admission orders on 24 patients.

Dr. Persoff plans to continue storm-chasing next year. But he says he’ll never forget the trauma nurse who was working as he arrived at Freeman and was still working as he left the hospital.

“That was one of the times where I was like, ‘Wow, this is really humbling,’ ” he says.

Check out photos and journal entries of Dr. Persoff’s storm-chasing adventures at http://stormdoctor.com/.