Lymphoma & Plasma Cell Disorders

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

LONDON – Low-dose irradiation of the stomach in patients with gastric MALT lymphoma absent or independent of infection by Helicobacter pylori is associated with a 93% disease control rate after 10 years.

As presented by Dr. Joachim Yahalom, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, these long-term study findings highlight the high disease-control rates that can be obtained using low-dose involved field radiotherapy (IFRT).

Low-dose IFRT has now become a standard of care in the United States, although approaches still vary in Europe, he reported May 9 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

Indeed, the latest guidelines set by the National Comprehensive Cancer Network on non-Hodgkin’s lymphomas – which includes gastric MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach – recommend the use of radiotherapy as a first-line option when patients have early (stage I/II) H. pylori–negative disease.

"We started using this [low-dose irradiation] treatment approach in the early 90s. Until then, the standard treatment for this lymphoma in the stomach was total gastrectomy, and sometimes it was followed by radiation therapy," said Dr. Yahalom, a professor of radiation oncology at Cornell University in New York. He added that chemotherapy and rituximab (Rituxan) were not generally very effective.

"Obviously the treatment of choice is to give antibiotics if H. pylori is present," Dr. Yahalom added, noting that substantial regression of MALT lymphoma can occur via treatment with antibiotics that target the gastric bacterium in positive cases. However, when H. pylori is not present, or if there is a lack of response to or residual lymphoma after complete response to antibiotic therapy, then radiotherapy is the recommended next step.

Dr. Yahalom presented data representing 16 years of experience in treating 103 patients (60 women and 43 men) with gastric MALT lymphoma in 1992-2009. The majority of patients (76%) had stage I disease, with 19% having stage II, and fewer than 5% having stage IV.

The median age of the patients was 62 years (range, 25-91 years). Symptoms were relatively mild at presentation, Dr. Yahalom observed: In all, 52% had epigastric pain, 36% had nausea, 29% had gastric bleeding, 18% had anorexia, 15% had anemia, and 10% had unknown or no obvious symptoms.

Almost two-thirds of patients were H. pylori negative. This included four patients who had relapsed after a complete response to antibiotic therapy. A further 20% of patients had persistent lymphoma after H. pylori eradication therapy. Another 15% had H. pylori and lymphoma remaining after antibiotic treatment, but had progressive symptoms or disease that could not wait for another antibiotics trial.

Prior to being treated with IFRT, six patients had undergone surgery, and seven had received medications that failed to control their disease.

Approximately 90% of patients were given IFRT at a median dose of 30 Gy in 1.5 Gy fractions for 4 weeks. The lowest and highest total radiation doses administered were 22.5 Gy and 43.5 Gy.

Patients received regular follow up via endoscopic biopsies, and after a median of 5.5 years, the disease control rate was 98%. One-fifth of patients had been followed for 10 years, and the 10-year freedom from local failure was 93%; the 10-year overall survival rate was 74%.

There were no significant acute or late adverse events, Dr. Yahalom noted, and just eight patients relapsed (six with gastric MALT lymphoma and two with diffuse large B-cell lymphoma). Subsequent other cancers included lymphoma in extragastric sites (eight patients), adenocarcinoma of the stomach (two), and second tumors close to the radiotherapy field (one in the colon and two in the pancreas). "Other deaths appeared unrelated to disease or treatment," he said.

Based on this experience, Dr. Yahalom concluded that "low-dose irradiation of the stomach provides excellent long-term disease control [and] is safe and simple.

"Radiation therapy, in our opinion, is the treatment of choice for patients with MALT lymphoma that have exhausted their antibiotic options or are unlikely to respond to it."

Dr. Yahalom said he had no financial conflicts of interest.

LONDON – Low-dose irradiation of the stomach in patients with gastric MALT lymphoma absent or independent of infection by Helicobacter pylori is associated with a 93% disease control rate after 10 years.

As presented by Dr. Joachim Yahalom, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, these long-term study findings highlight the high disease-control rates that can be obtained using low-dose involved field radiotherapy (IFRT).

Low-dose IFRT has now become a standard of care in the United States, although approaches still vary in Europe, he reported May 9 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

Indeed, the latest guidelines set by the National Comprehensive Cancer Network on non-Hodgkin’s lymphomas – which includes gastric MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach – recommend the use of radiotherapy as a first-line option when patients have early (stage I/II) H. pylori–negative disease.

"We started using this [low-dose irradiation] treatment approach in the early 90s. Until then, the standard treatment for this lymphoma in the stomach was total gastrectomy, and sometimes it was followed by radiation therapy," said Dr. Yahalom, a professor of radiation oncology at Cornell University in New York. He added that chemotherapy and rituximab (Rituxan) were not generally very effective.

"Obviously the treatment of choice is to give antibiotics if H. pylori is present," Dr. Yahalom added, noting that substantial regression of MALT lymphoma can occur via treatment with antibiotics that target the gastric bacterium in positive cases. However, when H. pylori is not present, or if there is a lack of response to or residual lymphoma after complete response to antibiotic therapy, then radiotherapy is the recommended next step.

Dr. Yahalom presented data representing 16 years of experience in treating 103 patients (60 women and 43 men) with gastric MALT lymphoma in 1992-2009. The majority of patients (76%) had stage I disease, with 19% having stage II, and fewer than 5% having stage IV.

The median age of the patients was 62 years (range, 25-91 years). Symptoms were relatively mild at presentation, Dr. Yahalom observed: In all, 52% had epigastric pain, 36% had nausea, 29% had gastric bleeding, 18% had anorexia, 15% had anemia, and 10% had unknown or no obvious symptoms.

Almost two-thirds of patients were H. pylori negative. This included four patients who had relapsed after a complete response to antibiotic therapy. A further 20% of patients had persistent lymphoma after H. pylori eradication therapy. Another 15% had H. pylori and lymphoma remaining after antibiotic treatment, but had progressive symptoms or disease that could not wait for another antibiotics trial.

Prior to being treated with IFRT, six patients had undergone surgery, and seven had received medications that failed to control their disease.

Approximately 90% of patients were given IFRT at a median dose of 30 Gy in 1.5 Gy fractions for 4 weeks. The lowest and highest total radiation doses administered were 22.5 Gy and 43.5 Gy.

Patients received regular follow up via endoscopic biopsies, and after a median of 5.5 years, the disease control rate was 98%. One-fifth of patients had been followed for 10 years, and the 10-year freedom from local failure was 93%; the 10-year overall survival rate was 74%.

There were no significant acute or late adverse events, Dr. Yahalom noted, and just eight patients relapsed (six with gastric MALT lymphoma and two with diffuse large B-cell lymphoma). Subsequent other cancers included lymphoma in extragastric sites (eight patients), adenocarcinoma of the stomach (two), and second tumors close to the radiotherapy field (one in the colon and two in the pancreas). "Other deaths appeared unrelated to disease or treatment," he said.

Based on this experience, Dr. Yahalom concluded that "low-dose irradiation of the stomach provides excellent long-term disease control [and] is safe and simple.

"Radiation therapy, in our opinion, is the treatment of choice for patients with MALT lymphoma that have exhausted their antibiotic options or are unlikely to respond to it."

Dr. Yahalom said he had no financial conflicts of interest.

LONDON – Low-dose irradiation of the stomach in patients with gastric MALT lymphoma absent or independent of infection by Helicobacter pylori is associated with a 93% disease control rate after 10 years.

As presented by Dr. Joachim Yahalom, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, these long-term study findings highlight the high disease-control rates that can be obtained using low-dose involved field radiotherapy (IFRT).

Low-dose IFRT has now become a standard of care in the United States, although approaches still vary in Europe, he reported May 9 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

Indeed, the latest guidelines set by the National Comprehensive Cancer Network on non-Hodgkin’s lymphomas – which includes gastric MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach – recommend the use of radiotherapy as a first-line option when patients have early (stage I/II) H. pylori–negative disease.

"We started using this [low-dose irradiation] treatment approach in the early 90s. Until then, the standard treatment for this lymphoma in the stomach was total gastrectomy, and sometimes it was followed by radiation therapy," said Dr. Yahalom, a professor of radiation oncology at Cornell University in New York. He added that chemotherapy and rituximab (Rituxan) were not generally very effective.

"Obviously the treatment of choice is to give antibiotics if H. pylori is present," Dr. Yahalom added, noting that substantial regression of MALT lymphoma can occur via treatment with antibiotics that target the gastric bacterium in positive cases. However, when H. pylori is not present, or if there is a lack of response to or residual lymphoma after complete response to antibiotic therapy, then radiotherapy is the recommended next step.

Dr. Yahalom presented data representing 16 years of experience in treating 103 patients (60 women and 43 men) with gastric MALT lymphoma in 1992-2009. The majority of patients (76%) had stage I disease, with 19% having stage II, and fewer than 5% having stage IV.

The median age of the patients was 62 years (range, 25-91 years). Symptoms were relatively mild at presentation, Dr. Yahalom observed: In all, 52% had epigastric pain, 36% had nausea, 29% had gastric bleeding, 18% had anorexia, 15% had anemia, and 10% had unknown or no obvious symptoms.

Almost two-thirds of patients were H. pylori negative. This included four patients who had relapsed after a complete response to antibiotic therapy. A further 20% of patients had persistent lymphoma after H. pylori eradication therapy. Another 15% had H. pylori and lymphoma remaining after antibiotic treatment, but had progressive symptoms or disease that could not wait for another antibiotics trial.

Prior to being treated with IFRT, six patients had undergone surgery, and seven had received medications that failed to control their disease.

Approximately 90% of patients were given IFRT at a median dose of 30 Gy in 1.5 Gy fractions for 4 weeks. The lowest and highest total radiation doses administered were 22.5 Gy and 43.5 Gy.

Patients received regular follow up via endoscopic biopsies, and after a median of 5.5 years, the disease control rate was 98%. One-fifth of patients had been followed for 10 years, and the 10-year freedom from local failure was 93%; the 10-year overall survival rate was 74%.

There were no significant acute or late adverse events, Dr. Yahalom noted, and just eight patients relapsed (six with gastric MALT lymphoma and two with diffuse large B-cell lymphoma). Subsequent other cancers included lymphoma in extragastric sites (eight patients), adenocarcinoma of the stomach (two), and second tumors close to the radiotherapy field (one in the colon and two in the pancreas). "Other deaths appeared unrelated to disease or treatment," he said.

Based on this experience, Dr. Yahalom concluded that "low-dose irradiation of the stomach provides excellent long-term disease control [and] is safe and simple.

"Radiation therapy, in our opinion, is the treatment of choice for patients with MALT lymphoma that have exhausted their antibiotic options or are unlikely to respond to it."

Dr. Yahalom said he had no financial conflicts of interest.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.

Cases of a rare, aggressive, and usually fatal lymphoma continue to be reported in people being treated with tumor necrosis factor blockers, azathioprine, and/or mercaptopurine, the Food and Drug Administration announced in an April 14 statement.

The reports of the lymphoma, hepatosplenic T-cell lymphoma (HSTCL), have primarily involved adolescents and young adults being treated with these agents for Crohn’s disease or ulcerative colitis. One patient, however, was being treated for psoriasis, and two others for rheumatoid arthritis.

Most patients were on a combination of treatments that are known to suppress the immune system, but there have been cases in patients taking azathioprine or mercaptopurine alone, the statement said.

"The risks and benefits of using TNF blockers, azathioprine, and/or mercaptopurine should be carefully weighed when prescribing these drugs to children and young adults, especially for the treatment of Crohn’s disease and ulcerative colitis," according to the FDA.

The statement recommends that health care professionals monitor patients on these treatments for malignancies and educate patients and their caregivers about the signs and symptoms of HSTCL, which can include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

The statement also notes that people with rheumatoid arthritis, Crohn’s, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis "may be more likely to develop lymphoma," compared with the general U.S. population, making it difficult to estimate the increased risk of malignancies associated with TNF blockers, azathioprine and/or mercaptopurine.

As of Dec. 31, 2010, the FDA’s Adverse Event Reporting System (AERS), the medical literature, and the Cancer Survivors Network had received the following unduplicated reports of HSTCL:

20 cases in patients taking infliximab (Remicade), including 18 patients also taking mercaptopurine or azathioprine.

• 1 case in a patient taking etanercept (Enbrel).

• 2 cases in patients taking adalimumab (Humira).

• 5 cases in patients taking a combination of infliximab and adalimumab (including 4 patients also taking mercaptopurine or azathioprine).

• 12 cases in patients taking azathioprine.

• 3 cases in patients taking mercaptopurine.

No cases have been reported in the TNF blockers certolizumab pegol (Cimzia) and golimumab (Simponi).

Reports of serious adverse events associated with these and other drugs should be reported online to the FDA’s MedWatch program or by phone to 800-332-1088.