CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.

First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).

Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.

Rituximab is not licensed for the treatment of MCL in Europe or the United States.

"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.

"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.

Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).

The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m²) was given as a single dose every 2 months until disease progression.

The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.

Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.

The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.

Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.

Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)

Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.

"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."

Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."

Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.

The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).

Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.

He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.

In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.

In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.

In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.

The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."

Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.

The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).

Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.

He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.

In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.

In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.

In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.

The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.

CHICAGO – It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology.

There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Half the population received R-CHOP every 3 weeks for eight cycles (R-CHOP-21), and the other half was assigned to R-CHOP every 2 weeks for six cycles, followed by two additional rituximab infusions (R-CHOP-14).

Dr. Cunningham highlighted the following findings:

• The 2-year overall survival rates were 81% in the R-CHOP-21 arm, and 83% in the R-CHOP-14 arm (log rank P = .70).

• Overall response rates (a combination of complete responses [CR], complete unconfirmed responses [CRu], and partial responses [PR]) were 88% in R-CHOP-21 and 90% in R-CHOP-14 (P = .11).

• Rates of combined CR/CRu were 63% and 58%, respectively (P = .15).

• The 2-year failure-free survival rates were identical, at 75% in each group.

Toxicities were also generally similar between the treatment groups, except for a lower incidence of neutropenia in the R-CHOP-14 arm, which reflected primary prophylaxis with granulocyte-colony-stimulating factor (G-CSF) in that group.

There were no differences in failure-free survival between the treatment arms when patients were stratified by age, sex, disease stage, bulky disease, B symptoms, prognostic score, IPI (International Prognostic Index) score, cell proliferation (as measured by the MIB-1 monoclonal antibody), or diffuse large B-cell lymphoma (DLBCL) phenotype.

"We couldn’t actually identify any of the subsets or subgroups that benefited from one or the other treatment," Dr. Cunningham said.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, commented that the study "compared some questions that have been burning in our minds for a long time," calling it a "very robust analysis of a very important study."

Summing up this study and three other abstracts that looked at alternative therapies for DLBCL, Dr. Vose said that R-CHOP-21 is still the standard of care for young patients with low, low/intermediate, or high/intermediate IPI scores, although R-CHOP-14 plus two rituximab infusions or R-CHOEP (R-CHOP plus etoposide) are acceptable alternatives. For young patients with high IPI, R-CHOP-21 followed by consolidation autologous transplant should be offered. For older patients, R-CHOP-21 for eight cycles is equivalent to R-CHOP-14 for six cycles plus two rituximab infusions.

The trial began recruiting after a 2004 German study showed that a dose-dense regimen of six cycles of CHOP-14 improved 5-year overall survival in patients older than 60 years by 13%, compared with six cycles of CHOP-21 (Blood 2004;104:634-41).

Since that publication, however, the addition of rituximab to six or eight cycles of CHOP or similar chemotherapy regimens was shown to improve overall survival of DLBCL by 10%-16% in two trials. Those findings raised interest in whether CHOP-14 might still be superior to CHOP-21 in patients who also receive rituximab, and whether such an effect would be seen across all age groups, Dr. Cunningham said.

He reported the final results of the trial, which involved 1,080 adults who had newly diagnosed CD20-positive DLBCL and were recruited from 119 sites. The patients were stratified by IPI score, age (60 years and younger, or older than 60), and treatment center.

In all, 23% of patients on R-CHOP-21 and 22% on R-CHOP-14 had died by the time of the final study analysis. DLBCL was the leading cause of death in both arms. Other causes included treatment-related toxicity, cardiac causes (all cardiac deaths occurred 3-15 months after completion of therapy), secondary malignancy, and other/unknown causes.

In her discussion, Dr. Vose pointed out that R-CHOP-14, which requires G-CSF support after every cycle, costs about $31,308, compared with $29,247 for R-CHOP-21, in which G-CSF is used only to treat (but not to prevent) neutropenia or febrile neutropenia. In the trial, G-CSF was used in 38% of R-CHOP-21 cycles, compared with 100% of R-CHOP-14 cycles.

In addition, R-CHOP every 21 days for six cycles (not eight) is generally considered to be the standard of care in the United States, she noted; a direct comparison of this shorter regimen with R-CHOP-14 would have been welcome, she said.

The trial was funded by the U.K. National Cancer Research Institute. The authors had no relevant financial disclosures.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

CHICAGO – Patients with high-risk, diffuse, aggressive non-Hodgkin’s lymphoma fared better when they received an autologous stem cell transplant during their first remission after chemotherapy than did similar patients who received standard chemotherapy alone, investigators reported at the annual meeting of the American Society of Clinical Oncology.

The estimated 2-year progression-free survival rate reached 69% among patients who were randomized to receive the CHOP regimen with or without rituximab for six cycles, followed by an autologous stem cell transplant (ASCT). In comparison, only 56% of patients who received eight cycles of CHOP with or without rituximab but no transplant were deemed progression free at that point (hazard ratio, 1.72; P = .0005).

The difference in progression-free survival has not yet led to a survival advantage, however, because patients who relapsed in the chemotherapy-only arm went on to transplant and have had generally good outcomes, Dr. Patrick J. Stiff of Loyola University Hospital, Maywood, Ill., reported on behalf of colleagues in the U.S./Canadian Intergroup trial SWOG S9704.

The 2-year estimated overall survival rate was 74% in transplanted patients and 71% in those who received chemotherapy alone (P = .16).

High-dose chemotherapy with ASCT is the standard of care for relapsed, diffuse, intermediate- and high-grade non-Hodgkin’s lymphoma (NHL) that is sensitive to chemotherapy. Several prospective trials have tested various combinations of high-dose therapy and transplant in patients in first complete remission, but with mixed results, Dr. Stiff noted.

In the absence of a better curative approach, the SWOG (Southwest Oncology Group) – in conjunction with the ECOG (Eastern Cooperative Oncology Group), CALGB (Cancer and Leukemia Group B), and the NCIC CTG (National Cancer Institute of Canada Clinical Trials Group) – started a prospective, randomized, phase III trial comparing six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by ASCT vs. eight cycles of CHOP for patients with high-intermediate and high IPI (International Prognostic Index) scores for diffuse, aggressive NHL.

The protocol was amended in 2003 to incorporate rituximab for all CD20-positive B-cell lymphomas, following results of other phase III trials that showed a significant survival advantage when the monoclonal antibody was added.

"While incorporation of rituximab into induction regimens has improved the outcome of patients with diffuse aggressive lymphomas, those with high-risk disease still have only about a 50% long-term survival," Dr. Stiff said.

All patients in the study received CHOP or R-CHOP (CHOP plus rituximab) for five cycles, with those having partial remission or better going on to randomization, and those having a response worse than partial remission being assigned to a different therapy off protocol.

For the randomization, patients were assigned to receive either one additional cycle of CHOP or R-CHOP followed by autologous transplant, or three additional cycles of CHOP/R-CHOP.

Of 397 patients registered in the trial, 253 were eligible for the randomization; 128 were assigned to chemotherapy only, and 125 to chemotherapy plus ASCT.

Following randomization, there were two toxicity-related deaths in the CHOP/R-CHOP–only arm, one from cardiovascular causes and the other from infection. One patient in this arm received rituximab only.

In the transplant arm, nine patients did not undergo ASCT; six of these patients died from treatment-related toxicity, including lung toxicities in three patients, and hemorrhage, infection, and graft-versus-host disease in one patient each.

"The postrelapse data indicate that the difference between the progression-free and overall survival was largely attributable to those patients who received a salvage transplant on the standard [chemotherapy-only] arm," Dr. Stiff said.

Nearly half (62) of those in the chemotherapy-only arm relapsed after therapy; of these, 29 underwent salvage autotransplantation, and 11 were in a second complete remission. An additional seven of those who relapsed had a second complete remission following alternative therapies.

A comparison of the effect of disease histology (B-cell vs. T-cell lymphoma) on outcome found no difference between autotransplantation and standard therapy. Looking at B-cell lymphomas only, the authors also found no evidence that rituximab had a differential effect.

Dr. Julie Vose of the University of Nebraska Medical Center in Omaha, the invited discussant, said that further analysis of subsets of patients are needed because, statistically, there were not enough patients who received rituximab for an analysis by IPI risk category.

Other questions that need to be answered are whether a complete response is necessary (or if a partial response would be adequate) for a patient to go on to transplantation, and whether there may be differential benefits to therapy for patients with activated B-cell lymphoma vs. germinal center B-cell, she said.

The trial was sponsored by the SWOG in collaboration with the ECOG, CALGB, the NCIC, and the U.S. National Cancer Institute. Dr. Stiff had no relevant relationships to disclose. Some coauthors have received honoraria or research funding from or serve as consultants to various drug companies.

Enacting comprehensive state laws that ban smoking in workplaces and restaurants as well as raising the cigarette tax by $1 per pack across the country could bring in billions in revenue for cash-strapped states, while also saving nearly 2 million lives, according to new estimates from the American Cancer Society Cancer Action Network.

The ACS CAN released two reports on June 15 that examined the public health benefits and economic savings from strengthening state antitobacco policies. In one report, researchers from the University of Illinois at Chicago looked at what would happen if the 27 states without comprehensive smoke-free laws were to enact such laws. In the second report, the same researchers considered the impact if all 50 states and the District of Columbia were to adopt a $1 per pack increase in the cigarette excise tax.

Photo credit: ©bilderbox/fotolia.com

"The bottom line is that strong tobacco control policies are a win-win for state legislators, for the states themselves, and [for] their constituents," said John R. Seffrin, Ph.D., chief executive officer of ACS CAN.

Currently, 23 states and the District of Columbia have enacted comprehensive laws that ban smoking in all bars, restaurants, and workplaces. The remaining 27 states have either less-comprehensive laws or no laws at all in this area. But when the researchers considered the impact if these 27 states were to adopt comprehensive smoking bans, they found that more than 1 million adults would quit smoking, nearly 400,000 children would never start smoking, and smoking-related deaths would fall by 624,000.

On the economic side, those 27 states would see a savings of about $316 million from lung cancer treatment, $875 million from heart attack and stroke treatment, and $128 million from smoking-related pregnancy treatment. And the researchers estimated that Medicaid programs in those 27 states would save a collective $42 million.

The report on tobacco taxes found similar public health and financial gains if a $1 per pack tax increase were enacted around the country. Such a tax would result in 1.4 million adults quitting smoking, 1.69 million children never starting to smoke, and 1.32 million fewer people dying from smoking-related causes. States also could benefit from both decreases in Medicaid spending and increased revenue. The report estimated that the tax would cut Medicaid spending by about $146 million across the states, and would bring in $8.62 billion in new state revenue.

Dr. Seffrin said that the results are attainable. An increasing number of states are adopting smoke-free laws and nearly all the states have increased cigarette excise taxes in recent years.

But he noted the ACS CAN is concerned that the tobacco industry is working to erode current tobacco-control laws at the state level. For example, there have been efforts in several states to add exemptions to the smoke-free laws.

Enacting comprehensive state laws that ban smoking in workplaces and restaurants as well as raising the cigarette tax by $1 per pack across the country could bring in billions in revenue for cash-strapped states, while also saving nearly 2 million lives, according to new estimates from the American Cancer Society Cancer Action Network.

The ACS CAN released two reports on June 15 that examined the public health benefits and economic savings from strengthening state antitobacco policies. In one report, researchers from the University of Illinois at Chicago looked at what would happen if the 27 states without comprehensive smoke-free laws were to enact such laws. In the second report, the same researchers considered the impact if all 50 states and the District of Columbia were to adopt a $1 per pack increase in the cigarette excise tax.

Photo credit: ©bilderbox/fotolia.com

"The bottom line is that strong tobacco control policies are a win-win for state legislators, for the states themselves, and [for] their constituents," said John R. Seffrin, Ph.D., chief executive officer of ACS CAN.

Currently, 23 states and the District of Columbia have enacted comprehensive laws that ban smoking in all bars, restaurants, and workplaces. The remaining 27 states have either less-comprehensive laws or no laws at all in this area. But when the researchers considered the impact if these 27 states were to adopt comprehensive smoking bans, they found that more than 1 million adults would quit smoking, nearly 400,000 children would never start smoking, and smoking-related deaths would fall by 624,000.

On the economic side, those 27 states would see a savings of about $316 million from lung cancer treatment, $875 million from heart attack and stroke treatment, and $128 million from smoking-related pregnancy treatment. And the researchers estimated that Medicaid programs in those 27 states would save a collective $42 million.

The report on tobacco taxes found similar public health and financial gains if a $1 per pack tax increase were enacted around the country. Such a tax would result in 1.4 million adults quitting smoking, 1.69 million children never starting to smoke, and 1.32 million fewer people dying from smoking-related causes. States also could benefit from both decreases in Medicaid spending and increased revenue. The report estimated that the tax would cut Medicaid spending by about $146 million across the states, and would bring in $8.62 billion in new state revenue.

Dr. Seffrin said that the results are attainable. An increasing number of states are adopting smoke-free laws and nearly all the states have increased cigarette excise taxes in recent years.

But he noted the ACS CAN is concerned that the tobacco industry is working to erode current tobacco-control laws at the state level. For example, there have been efforts in several states to add exemptions to the smoke-free laws.

Enacting comprehensive state laws that ban smoking in workplaces and restaurants as well as raising the cigarette tax by $1 per pack across the country could bring in billions in revenue for cash-strapped states, while also saving nearly 2 million lives, according to new estimates from the American Cancer Society Cancer Action Network.

The ACS CAN released two reports on June 15 that examined the public health benefits and economic savings from strengthening state antitobacco policies. In one report, researchers from the University of Illinois at Chicago looked at what would happen if the 27 states without comprehensive smoke-free laws were to enact such laws. In the second report, the same researchers considered the impact if all 50 states and the District of Columbia were to adopt a $1 per pack increase in the cigarette excise tax.

Photo credit: ©bilderbox/fotolia.com

"The bottom line is that strong tobacco control policies are a win-win for state legislators, for the states themselves, and [for] their constituents," said John R. Seffrin, Ph.D., chief executive officer of ACS CAN.

Currently, 23 states and the District of Columbia have enacted comprehensive laws that ban smoking in all bars, restaurants, and workplaces. The remaining 27 states have either less-comprehensive laws or no laws at all in this area. But when the researchers considered the impact if these 27 states were to adopt comprehensive smoking bans, they found that more than 1 million adults would quit smoking, nearly 400,000 children would never start smoking, and smoking-related deaths would fall by 624,000.

On the economic side, those 27 states would see a savings of about $316 million from lung cancer treatment, $875 million from heart attack and stroke treatment, and $128 million from smoking-related pregnancy treatment. And the researchers estimated that Medicaid programs in those 27 states would save a collective $42 million.

The report on tobacco taxes found similar public health and financial gains if a $1 per pack tax increase were enacted around the country. Such a tax would result in 1.4 million adults quitting smoking, 1.69 million children never starting to smoke, and 1.32 million fewer people dying from smoking-related causes. States also could benefit from both decreases in Medicaid spending and increased revenue. The report estimated that the tax would cut Medicaid spending by about $146 million across the states, and would bring in $8.62 billion in new state revenue.

Dr. Seffrin said that the results are attainable. An increasing number of states are adopting smoke-free laws and nearly all the states have increased cigarette excise taxes in recent years.

But he noted the ACS CAN is concerned that the tobacco industry is working to erode current tobacco-control laws at the state level. For example, there have been efforts in several states to add exemptions to the smoke-free laws.

The first wave of fiscal year 2010 (FY10) provider data from SHM-MGMA shows that hospitalist salaries and productivity appear to have to have crept up only slightly from the previous year.

The national median annual salary for internal-medicine hospitalists seeing adult patients is $220,144, up from $215,000 in FY09, a 2.4% increase. For pediatric hospitalists, the 2010 salary was $171,617, up from $160,038 in FY09, a 7% increase. Work RVUs for both categories saw even smaller increases: 4,174 for internal-medicine hospitalists (up 1.8%) and 1,976 for pediatric hospitalists (up 0.02%).

By comparison, the increase from SHM's 2007-2008 survey to 2009's salary data set from SHM-MGMA was 9%. SHM cautions against drawing too many conclusions from comparisons with older figures, as the population universes are different. However, Leslie Flores, MHA, SHM senior advisor for practice management, says that anecdotally, the data suggest the field is hitting a fiscal plateau.

"What I get out of this is both compensation and productivity appear to be leveling off somewhat," Flores says. "We're not seeing the big increases from year to year we have seen historically."

The data are publicly available as of today, even though snippets of the survey results were previewed at HM11 last month in Grapevine, Texas. The preview, however, only showed regional figures. Academic hospitalist data was removed from the study this year, as that provider universe now has its own survey.

Flores says it's hard to pin down exactly why increases in both salaries and productivity are slowing. It could be the natural evolution of the relatively young field, or it could be a narrowing of the supply-demand gap for hospitalists.

The data being released today serve as the foundation for the annual State of Hospital Medicine report, scheduled for release in September. That expanded data set will feature HM-centric data points including CPT code distribution, group leader compensation, and administrative time allocation and compensation and productivity for nocturnists. Until then, Flores says, hospitalists should consider data points like the ones currently available as key negotiating and practice-management guideposts. But national data only go so far.

"Even the regional numbers don't reflect what the individual numbers are in individual markets. You need to know what the hospitalist down the street is making," she says.

The first wave of fiscal year 2010 (FY10) provider data from SHM-MGMA shows that hospitalist salaries and productivity appear to have to have crept up only slightly from the previous year.

The national median annual salary for internal-medicine hospitalists seeing adult patients is $220,144, up from $215,000 in FY09, a 2.4% increase. For pediatric hospitalists, the 2010 salary was $171,617, up from $160,038 in FY09, a 7% increase. Work RVUs for both categories saw even smaller increases: 4,174 for internal-medicine hospitalists (up 1.8%) and 1,976 for pediatric hospitalists (up 0.02%).

By comparison, the increase from SHM's 2007-2008 survey to 2009's salary data set from SHM-MGMA was 9%. SHM cautions against drawing too many conclusions from comparisons with older figures, as the population universes are different. However, Leslie Flores, MHA, SHM senior advisor for practice management, says that anecdotally, the data suggest the field is hitting a fiscal plateau.

"What I get out of this is both compensation and productivity appear to be leveling off somewhat," Flores says. "We're not seeing the big increases from year to year we have seen historically."

The data are publicly available as of today, even though snippets of the survey results were previewed at HM11 last month in Grapevine, Texas. The preview, however, only showed regional figures. Academic hospitalist data was removed from the study this year, as that provider universe now has its own survey.

Flores says it's hard to pin down exactly why increases in both salaries and productivity are slowing. It could be the natural evolution of the relatively young field, or it could be a narrowing of the supply-demand gap for hospitalists.

The data being released today serve as the foundation for the annual State of Hospital Medicine report, scheduled for release in September. That expanded data set will feature HM-centric data points including CPT code distribution, group leader compensation, and administrative time allocation and compensation and productivity for nocturnists. Until then, Flores says, hospitalists should consider data points like the ones currently available as key negotiating and practice-management guideposts. But national data only go so far.

"Even the regional numbers don't reflect what the individual numbers are in individual markets. You need to know what the hospitalist down the street is making," she says.

The first wave of fiscal year 2010 (FY10) provider data from SHM-MGMA shows that hospitalist salaries and productivity appear to have to have crept up only slightly from the previous year.

The national median annual salary for internal-medicine hospitalists seeing adult patients is $220,144, up from $215,000 in FY09, a 2.4% increase. For pediatric hospitalists, the 2010 salary was $171,617, up from $160,038 in FY09, a 7% increase. Work RVUs for both categories saw even smaller increases: 4,174 for internal-medicine hospitalists (up 1.8%) and 1,976 for pediatric hospitalists (up 0.02%).

By comparison, the increase from SHM's 2007-2008 survey to 2009's salary data set from SHM-MGMA was 9%. SHM cautions against drawing too many conclusions from comparisons with older figures, as the population universes are different. However, Leslie Flores, MHA, SHM senior advisor for practice management, says that anecdotally, the data suggest the field is hitting a fiscal plateau.

"What I get out of this is both compensation and productivity appear to be leveling off somewhat," Flores says. "We're not seeing the big increases from year to year we have seen historically."

The data are publicly available as of today, even though snippets of the survey results were previewed at HM11 last month in Grapevine, Texas. The preview, however, only showed regional figures. Academic hospitalist data was removed from the study this year, as that provider universe now has its own survey.

Flores says it's hard to pin down exactly why increases in both salaries and productivity are slowing. It could be the natural evolution of the relatively young field, or it could be a narrowing of the supply-demand gap for hospitalists.

The data being released today serve as the foundation for the annual State of Hospital Medicine report, scheduled for release in September. That expanded data set will feature HM-centric data points including CPT code distribution, group leader compensation, and administrative time allocation and compensation and productivity for nocturnists. Until then, Flores says, hospitalists should consider data points like the ones currently available as key negotiating and practice-management guideposts. But national data only go so far.

"Even the regional numbers don't reflect what the individual numbers are in individual markets. You need to know what the hospitalist down the street is making," she says.

Several recently published studies have documented a variety of disparities in the provision of end-of-life care. In some cases, these disparities reflect socio-economic and cultural differences, information that could help hospitalists respond appropriately to different patients’ needs, says Tochi Iroku-Malize, MD, MPH, SFHM, chair of family medicine at North Shore-Long Island Jewish Health System in Great Neck, N.Y.

"One approach does not fit all patients," says Dr. Iroku-Malize, a former HM group director who is board-certified in hospice and palliative medicine. "If you understand that end-of-life care is important, and you know about disparities in care, you will understand the need to deal with these diverse populations."

Hospitalists should appreciate that even if they are not able to refer a seriously ill patient to palliative care or hospice during an initial acute encounter, they can plant a seed for subsequent conversations. They should also report these conversations back to the primary-care physician (PCP), as they would for other medical treatments, she adds.

Racial and ethnic differences independent of socio-economic status are seen in end-of-life care in ICUs, reports the journal Chest (2011;139(5):1025-1033). Nonwhite patients are less likely to have living wills and more likely to die on full life support, to have a documented family conference where prognosis was discussed, and to have discord within the family or with the physician over treatment choices.

A phone survey of cancer patients found that black patients are more likely than white patients to spend everything they have on aggressive treatments that might prolong their lives, regardless of how sick they are, their income, savings, or age. In addition, the Dartmouth Atlas of Health's recent report "Trends and Variations in End-of-Life Care for Medicare Beneficiaries with Severe Chronic Illness" (PDF) found persistent evidence of widespread geographical differences in end-of-life care. In the last six months of their lives, chronically ill Medicare beneficiaries in some regions of the country spent three times as many days in the hospital and 10 times as many days in the ICU as patients in other regions.

Another survey found PCPs are more likely to choose for themselves treatments with higher rates of death but lower rates of adverse events than they would recommend to their patients (Arch Int Med 2011;171:630-634).

Several recently published studies have documented a variety of disparities in the provision of end-of-life care. In some cases, these disparities reflect socio-economic and cultural differences, information that could help hospitalists respond appropriately to different patients’ needs, says Tochi Iroku-Malize, MD, MPH, SFHM, chair of family medicine at North Shore-Long Island Jewish Health System in Great Neck, N.Y.

"One approach does not fit all patients," says Dr. Iroku-Malize, a former HM group director who is board-certified in hospice and palliative medicine. "If you understand that end-of-life care is important, and you know about disparities in care, you will understand the need to deal with these diverse populations."

Hospitalists should appreciate that even if they are not able to refer a seriously ill patient to palliative care or hospice during an initial acute encounter, they can plant a seed for subsequent conversations. They should also report these conversations back to the primary-care physician (PCP), as they would for other medical treatments, she adds.

Racial and ethnic differences independent of socio-economic status are seen in end-of-life care in ICUs, reports the journal Chest (2011;139(5):1025-1033). Nonwhite patients are less likely to have living wills and more likely to die on full life support, to have a documented family conference where prognosis was discussed, and to have discord within the family or with the physician over treatment choices.

A phone survey of cancer patients found that black patients are more likely than white patients to spend everything they have on aggressive treatments that might prolong their lives, regardless of how sick they are, their income, savings, or age. In addition, the Dartmouth Atlas of Health's recent report "Trends and Variations in End-of-Life Care for Medicare Beneficiaries with Severe Chronic Illness" (PDF) found persistent evidence of widespread geographical differences in end-of-life care. In the last six months of their lives, chronically ill Medicare beneficiaries in some regions of the country spent three times as many days in the hospital and 10 times as many days in the ICU as patients in other regions.

Another survey found PCPs are more likely to choose for themselves treatments with higher rates of death but lower rates of adverse events than they would recommend to their patients (Arch Int Med 2011;171:630-634).

Several recently published studies have documented a variety of disparities in the provision of end-of-life care. In some cases, these disparities reflect socio-economic and cultural differences, information that could help hospitalists respond appropriately to different patients’ needs, says Tochi Iroku-Malize, MD, MPH, SFHM, chair of family medicine at North Shore-Long Island Jewish Health System in Great Neck, N.Y.

"One approach does not fit all patients," says Dr. Iroku-Malize, a former HM group director who is board-certified in hospice and palliative medicine. "If you understand that end-of-life care is important, and you know about disparities in care, you will understand the need to deal with these diverse populations."

Hospitalists should appreciate that even if they are not able to refer a seriously ill patient to palliative care or hospice during an initial acute encounter, they can plant a seed for subsequent conversations. They should also report these conversations back to the primary-care physician (PCP), as they would for other medical treatments, she adds.

Racial and ethnic differences independent of socio-economic status are seen in end-of-life care in ICUs, reports the journal Chest (2011;139(5):1025-1033). Nonwhite patients are less likely to have living wills and more likely to die on full life support, to have a documented family conference where prognosis was discussed, and to have discord within the family or with the physician over treatment choices.

A phone survey of cancer patients found that black patients are more likely than white patients to spend everything they have on aggressive treatments that might prolong their lives, regardless of how sick they are, their income, savings, or age. In addition, the Dartmouth Atlas of Health's recent report "Trends and Variations in End-of-Life Care for Medicare Beneficiaries with Severe Chronic Illness" (PDF) found persistent evidence of widespread geographical differences in end-of-life care. In the last six months of their lives, chronically ill Medicare beneficiaries in some regions of the country spent three times as many days in the hospital and 10 times as many days in the ICU as patients in other regions.

Another survey found PCPs are more likely to choose for themselves treatments with higher rates of death but lower rates of adverse events than they would recommend to their patients (Arch Int Med 2011;171:630-634).

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.

CHICAGO – Data from the prospective, phase-III EURTAC trial cement the need for personalized treatment of lung cancer patients but also leave clinicians in uncharted waters in terms of treatment options.

First-line erlotinib (Tarceva) improved the primary end point of progression-free survival from 5.2 months with standard platinum-based chemotherapy to 9.4 months in white patients who had advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations in an interim analysis.

Study cochair Dr. Rafael Rosell, president of the Spanish Lung Cancer Group, reported a significant 63% reduction in the risk of progression (hazard ratio, 0.37; log-rank P less than .0001) in an updated analysis presented at the annual meeting of the American Society of Clinical Oncology.

Based on positive results in the earlier interim analysis, Genentech and partner OSI Pharmaceuticals announced in January that the trial had been halted and they were set to pursue a broader indication for erlotinib as first-line treatment in NSCLC with EGFR mutations.

Erlotinib, a tyrosine kinase inhibitor (TKI), is approved in the United States and Europe as a maintenance and second-line treatment for advanced or metastatic NSCLC with and without EGFR activating mutations. Genentech’s parent company, Roche, submitted a bid to the European Medicines Agency in June 2010 to expand the drug’s label.

Even though the proverbial cat had already been let out of the bag by the drug makers, EURTAC caused a stir at ASCO, where the full data were formally presented and the study was chosen as one of the Best of ASCO 2011.

Invited discussant Dr. Tony Mok of the Chinese University of Hong Kong called the data trustworthy and a true reflection of erlotinib’s efficacy in patients with EGFR mutations. He drew parallels between EURTAC and the OPTIMAL trial in which erlotinib proved potent among Asians with this genetically distinct form of lung cancer. EGFR mutations are present in about 10% of patients in the West and about 30% of Asians, and they are associated with an increased response to erlotinib and the TKI gefitinib (Iressa).

Dr. Mok said that there’s a good chance erlotinib will be approved as first-line therapy. The EURTAC data are on par with the IPASS trial that helped gain approval for gefitinib (Iressa) as first-line therapy for patients with EGFR mutations in more than 70 countries, except the United States, where gefitinib use is restricted and AstraZeneca has said it will not seek a new indication for the drug.

"Now we have two drugs," said Dr. Mok, principal investigator of IPASS. "What are we going to do when faced with an EGFR mutation? Is there a difference in terms of the effectiveness between the TKIs in patients with EGFR mutations? That is the million-dollar question or the billion-dollar question."

Dr. Mok pointed out that three other TKIs are in the pipeline for patients with EGFR mutations, including icotinib (Zhejang BetaPharma); afatinib (Boehringer Ingelheim), which binds EGFR and inhibits HER2; and the oral, once-daily PF-299804 (Pfizer). A poster presented at ASCO on the phase-III ICOGEN trial reported that icotinib provides similar overall efficacy and better tolerability than gefitinib in patients with NSCLC who progressed after one to two lines of chemotherapy; it also improved efficacy in a subset of EGFR-mutant patient.

The EURTAC trial randomly assigned 174 chemo-naive, stage IIIB/IV NSCLC patients with exon 19 deletions or L858R mutations to receive erlotinib 150 mg/day or platinum-based doublet chemotherapy every 3 weeks for four cycles. The doublet could include cisplatin 75 mg/m² on day 1 plus docetaxel 75 mg/m² on day 1; cisplatin 75 mg/m² on day 1 plus gemcitabine 1,250 mg/m² on days 1 and 8; carboplatin area under the curve (AUC) 6 on day 1 plus docetaxel 75 mg/m² on day 1 or carboplatin AUC 5 on day 1 plus gemcitabine 1,000 mg/m² on days 1 and 8.

The objective response rate was 58% for erlotinib vs. 15% for chemotherapy in the updated analysis, said Dr. Rosell, head of medical oncology at the Catalan Institute of Oncology in Barcelona. At the time of the interim analysis, two patients had a complete response to erlotinib and 40 had partial responses, with 8 additional partial responses reported in the updated analysis. No patient had a complete response with chemotherapy, eight patients had partial responses early on, and five more reported partial responses in the updated analysis.

The disease control rate in the interim analysis was 79% for erlotinib vs. 66% in the updated analysis.

Median overall survival was 18.8 months with chemotherapy and 22.9 months in the interim analysis (hazard ratio, 0.80; log rank P = 0.42). As of the Jan. 26, 2011 cutoff date for the updated analysis, 94 patients remain in overall survival follow-up, with a high level of known crossover, Dr. Rosell said. A subgroup analysis suggested that progression-free survival was better in patients with a performance status of 0, never-smokers, and those with an exon 19 deletion.

The majority of patients who relapsed on erlotinib were switched to chemotherapy. The tolerability of erlotinib was consistent with previous studies, he noted.

The Spanish Lung Cancer Group sponsored the trial. Dr. Rosell disclosed a consultant/advisory role with Roche. Two of his coauthors reported a similar role, with one also providing expert testimony for Roche. Dr. Mok disclosed relationships with several drug companies, including AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer.