Lymphoma & Plasma Cell Disorders

NEW ORLEANS – For patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplants, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and progression-free survival benefits, compared with melphalan-prednisone-thalidomide.

"Overall, we should congratulate [the investigators] for having a new standard of care that is active, convenient, and with excellent tolerability," said invited discussant Dr. Jesús San Miguel from the cancer center at the Hospital Universitario de Salamanca, Spain.

Initial results from the phase III FIRST trial (Front-Line Investigation of Revlimid/Dexamethasone vs. Standard Thalidomide) showed that lenalidomide (Revlimid [RD]) plus low-dose dexamethasone used until disease progression was associated with a median progression-free survival (PFS, the primary endpoint) of 25.5 months, compared with 20.7 months for patients treated with the same combination for 18 cycles over 72 weeks (RD18), and 21.2 months for patients treated with melphalan-prednisone-thalidomide (MPT) for 12 cycles over 72 weeks, reported Dr. Thierry Facon of the Service des Maladies du Sang, Hôpital Claude Huriez and CHRU Lille, France.

At the first interim analysis, patients treated with continuous RD had better overall survival than patients treated with MPT, with a hazard ratio favoring RD of 0.78 (P = .0168). However, there were no significant differences in overall survival between the RD and RD18 groups or between the RD18 and MPT groups, Dr. Facon said at the American Society of Hematology annual meeting.

The FIRST trial investigators enrolled 1,623 patients aged 65 years or older from 246 centers in 18 countries in North America, Europe, Asia, and Australia/New Zealand. Patients were randomly assigned to either continuous RD (535), RD18 (541), or MPT (547). Median follow-up as of May 24, 2013, was 37 months.

Continuous RD offered significantly better PFS, compared with either RD18 or MPT. At 3 years, 42% of patients on continuous RD remained progression free, compared with 23% each in the other two groups. The hazard ratio for continuous RD vs. MPT was 0.72 (P = .00006), and vs. RD18 was 0.70 (P = .00001). There was no significant difference in progression-free survival between RD18 and MPT.

Estimated 4-year overall survival rates were 59.4% in the continuous RD group, 55.7% in the RD18 group, and 51.4% in the MPT group.

"RD was superior to MPT across all other efficacy secondary endpoints," Dr. Facon said in the plenary session. Those secondary endpoints included response, duration of response, time to response, time to treatment failure, time to second-line anti–multiple myeloma therapy, time to progression, safety, and quality of life.

Both versions of the RD regimen were generally comparable to MPT in safety profile, although infections were more frequent with RD, and peripheral sensory neuropathy was more frequent with continuous RD (1.1% vs. 0.4% for the other two regimens).

The incidence of second primary malignancies was lower in both RD groups, consisting of one case each of acute myeloid leukemia and myelodysplasia in each group, compared with four cases of acute myeloid leukemia, six of myelodysplasia, and two cases of myelodysplasia converting to acute myeloid leukemia in the MPT group.

Current treatment approaches for elderly, newly diagnosed patients with multiple myeloma include MPT, which is associated with a PFS of 20.3 months; and bortezomib (Velcade), melphalan, and prednisone (VMP), with a PFS of 18.3 months. MPT and VMP are the preferred regimens recommend by the National Comprehensive Cancer Network for patients who are ineligible for stem cell transplants because of age or other factors, Dr. Facon noted. Typically, drug therapy in this patient population has had a fixed duration because of f concern for toxicities associated with long-term therapy.

Dr. San Miguel noted that the excellent results were achieved without the use of an alkylating agent such as melphalan or cyclophosphamide, which might lead some clinicians to question whether alkylating agents still have a role in this population. He pointed out, however, that the study was not designed to answer that question. To do so, it would be necessary to compare RD with and without an alkylator for the same treatment duration.

"Probably the most challenging question is the duration of the lenalidomide treatment. The data indicate that the best option is to treat until progression. Nevertheless, it would be interesting to know the outcome according to response, because it could be that in patients taking lenalidomide and dexamethasone for 1 year or [1 1/2 years] will achieve a complete response with prolonged disease stability. Additional treatment may not add too much, and this could contribute to increased cost and toxicities of unnecessary prolonged treatment," he said.

Questions that still need to be answered include benefits for specific populations, such as high-risk patients, the very elderly, and those with renal insufficiency. It’s also unclear whether the reduced risk of secondary malignancies is because of the absence of melphalan or the presence of dexamethasone.

It will also be important to find a way to indentify, as early as possible, the 25% of patients who will not achieve at least a partial response, he said.

The study was supported by Celegene Corporation and by the Intergroupe Francophone du Myelome. Dr. Facon disclosed serving on the speakers bureau and being a member on a board of directors/advisory committee for Celgene. Dr. San Miguel reported having no disclosures.

NEW ORLEANS – For patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplants, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and progression-free survival benefits, compared with melphalan-prednisone-thalidomide.

"Overall, we should congratulate [the investigators] for having a new standard of care that is active, convenient, and with excellent tolerability," said invited discussant Dr. Jesús San Miguel from the cancer center at the Hospital Universitario de Salamanca, Spain.

Initial results from the phase III FIRST trial (Front-Line Investigation of Revlimid/Dexamethasone vs. Standard Thalidomide) showed that lenalidomide (Revlimid [RD]) plus low-dose dexamethasone used until disease progression was associated with a median progression-free survival (PFS, the primary endpoint) of 25.5 months, compared with 20.7 months for patients treated with the same combination for 18 cycles over 72 weeks (RD18), and 21.2 months for patients treated with melphalan-prednisone-thalidomide (MPT) for 12 cycles over 72 weeks, reported Dr. Thierry Facon of the Service des Maladies du Sang, Hôpital Claude Huriez and CHRU Lille, France.

At the first interim analysis, patients treated with continuous RD had better overall survival than patients treated with MPT, with a hazard ratio favoring RD of 0.78 (P = .0168). However, there were no significant differences in overall survival between the RD and RD18 groups or between the RD18 and MPT groups, Dr. Facon said at the American Society of Hematology annual meeting.

The FIRST trial investigators enrolled 1,623 patients aged 65 years or older from 246 centers in 18 countries in North America, Europe, Asia, and Australia/New Zealand. Patients were randomly assigned to either continuous RD (535), RD18 (541), or MPT (547). Median follow-up as of May 24, 2013, was 37 months.

Continuous RD offered significantly better PFS, compared with either RD18 or MPT. At 3 years, 42% of patients on continuous RD remained progression free, compared with 23% each in the other two groups. The hazard ratio for continuous RD vs. MPT was 0.72 (P = .00006), and vs. RD18 was 0.70 (P = .00001). There was no significant difference in progression-free survival between RD18 and MPT.

Estimated 4-year overall survival rates were 59.4% in the continuous RD group, 55.7% in the RD18 group, and 51.4% in the MPT group.

"RD was superior to MPT across all other efficacy secondary endpoints," Dr. Facon said in the plenary session. Those secondary endpoints included response, duration of response, time to response, time to treatment failure, time to second-line anti–multiple myeloma therapy, time to progression, safety, and quality of life.

Both versions of the RD regimen were generally comparable to MPT in safety profile, although infections were more frequent with RD, and peripheral sensory neuropathy was more frequent with continuous RD (1.1% vs. 0.4% for the other two regimens).

The incidence of second primary malignancies was lower in both RD groups, consisting of one case each of acute myeloid leukemia and myelodysplasia in each group, compared with four cases of acute myeloid leukemia, six of myelodysplasia, and two cases of myelodysplasia converting to acute myeloid leukemia in the MPT group.

Current treatment approaches for elderly, newly diagnosed patients with multiple myeloma include MPT, which is associated with a PFS of 20.3 months; and bortezomib (Velcade), melphalan, and prednisone (VMP), with a PFS of 18.3 months. MPT and VMP are the preferred regimens recommend by the National Comprehensive Cancer Network for patients who are ineligible for stem cell transplants because of age or other factors, Dr. Facon noted. Typically, drug therapy in this patient population has had a fixed duration because of f concern for toxicities associated with long-term therapy.

Dr. San Miguel noted that the excellent results were achieved without the use of an alkylating agent such as melphalan or cyclophosphamide, which might lead some clinicians to question whether alkylating agents still have a role in this population. He pointed out, however, that the study was not designed to answer that question. To do so, it would be necessary to compare RD with and without an alkylator for the same treatment duration.

"Probably the most challenging question is the duration of the lenalidomide treatment. The data indicate that the best option is to treat until progression. Nevertheless, it would be interesting to know the outcome according to response, because it could be that in patients taking lenalidomide and dexamethasone for 1 year or [1 1/2 years] will achieve a complete response with prolonged disease stability. Additional treatment may not add too much, and this could contribute to increased cost and toxicities of unnecessary prolonged treatment," he said.

Questions that still need to be answered include benefits for specific populations, such as high-risk patients, the very elderly, and those with renal insufficiency. It’s also unclear whether the reduced risk of secondary malignancies is because of the absence of melphalan or the presence of dexamethasone.

It will also be important to find a way to indentify, as early as possible, the 25% of patients who will not achieve at least a partial response, he said.

The study was supported by Celegene Corporation and by the Intergroupe Francophone du Myelome. Dr. Facon disclosed serving on the speakers bureau and being a member on a board of directors/advisory committee for Celgene. Dr. San Miguel reported having no disclosures.

NEW ORLEANS – For patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplants, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and progression-free survival benefits, compared with melphalan-prednisone-thalidomide.

"Overall, we should congratulate [the investigators] for having a new standard of care that is active, convenient, and with excellent tolerability," said invited discussant Dr. Jesús San Miguel from the cancer center at the Hospital Universitario de Salamanca, Spain.

Initial results from the phase III FIRST trial (Front-Line Investigation of Revlimid/Dexamethasone vs. Standard Thalidomide) showed that lenalidomide (Revlimid [RD]) plus low-dose dexamethasone used until disease progression was associated with a median progression-free survival (PFS, the primary endpoint) of 25.5 months, compared with 20.7 months for patients treated with the same combination for 18 cycles over 72 weeks (RD18), and 21.2 months for patients treated with melphalan-prednisone-thalidomide (MPT) for 12 cycles over 72 weeks, reported Dr. Thierry Facon of the Service des Maladies du Sang, Hôpital Claude Huriez and CHRU Lille, France.

At the first interim analysis, patients treated with continuous RD had better overall survival than patients treated with MPT, with a hazard ratio favoring RD of 0.78 (P = .0168). However, there were no significant differences in overall survival between the RD and RD18 groups or between the RD18 and MPT groups, Dr. Facon said at the American Society of Hematology annual meeting.

The FIRST trial investigators enrolled 1,623 patients aged 65 years or older from 246 centers in 18 countries in North America, Europe, Asia, and Australia/New Zealand. Patients were randomly assigned to either continuous RD (535), RD18 (541), or MPT (547). Median follow-up as of May 24, 2013, was 37 months.

Continuous RD offered significantly better PFS, compared with either RD18 or MPT. At 3 years, 42% of patients on continuous RD remained progression free, compared with 23% each in the other two groups. The hazard ratio for continuous RD vs. MPT was 0.72 (P = .00006), and vs. RD18 was 0.70 (P = .00001). There was no significant difference in progression-free survival between RD18 and MPT.

Estimated 4-year overall survival rates were 59.4% in the continuous RD group, 55.7% in the RD18 group, and 51.4% in the MPT group.

"RD was superior to MPT across all other efficacy secondary endpoints," Dr. Facon said in the plenary session. Those secondary endpoints included response, duration of response, time to response, time to treatment failure, time to second-line anti–multiple myeloma therapy, time to progression, safety, and quality of life.

Both versions of the RD regimen were generally comparable to MPT in safety profile, although infections were more frequent with RD, and peripheral sensory neuropathy was more frequent with continuous RD (1.1% vs. 0.4% for the other two regimens).

The incidence of second primary malignancies was lower in both RD groups, consisting of one case each of acute myeloid leukemia and myelodysplasia in each group, compared with four cases of acute myeloid leukemia, six of myelodysplasia, and two cases of myelodysplasia converting to acute myeloid leukemia in the MPT group.

Current treatment approaches for elderly, newly diagnosed patients with multiple myeloma include MPT, which is associated with a PFS of 20.3 months; and bortezomib (Velcade), melphalan, and prednisone (VMP), with a PFS of 18.3 months. MPT and VMP are the preferred regimens recommend by the National Comprehensive Cancer Network for patients who are ineligible for stem cell transplants because of age or other factors, Dr. Facon noted. Typically, drug therapy in this patient population has had a fixed duration because of f concern for toxicities associated with long-term therapy.

Dr. San Miguel noted that the excellent results were achieved without the use of an alkylating agent such as melphalan or cyclophosphamide, which might lead some clinicians to question whether alkylating agents still have a role in this population. He pointed out, however, that the study was not designed to answer that question. To do so, it would be necessary to compare RD with and without an alkylator for the same treatment duration.

"Probably the most challenging question is the duration of the lenalidomide treatment. The data indicate that the best option is to treat until progression. Nevertheless, it would be interesting to know the outcome according to response, because it could be that in patients taking lenalidomide and dexamethasone for 1 year or [1 1/2 years] will achieve a complete response with prolonged disease stability. Additional treatment may not add too much, and this could contribute to increased cost and toxicities of unnecessary prolonged treatment," he said.

Questions that still need to be answered include benefits for specific populations, such as high-risk patients, the very elderly, and those with renal insufficiency. It’s also unclear whether the reduced risk of secondary malignancies is because of the absence of melphalan or the presence of dexamethasone.

It will also be important to find a way to indentify, as early as possible, the 25% of patients who will not achieve at least a partial response, he said.

The study was supported by Celegene Corporation and by the Intergroupe Francophone du Myelome. Dr. Facon disclosed serving on the speakers bureau and being a member on a board of directors/advisory committee for Celgene. Dr. San Miguel reported having no disclosures.

NEW ORLEANS – A majority of patients with aggressive, treatment-refractory lymphomas had a complete or partial remission after being treated with chemotherapy and T-cells engineered to target the CD-19 receptor, National Cancer Institute investigators reported here.

In a study of 15 patients, 9 of whom had aggressive large-cell lymphomas and 6 of whom had indolent B-cell malignancies, 6 of 13 evaluable patients had a complete remission, 6 had a partial remission, and 1 had stable disease, said Dr. James N. Kochenderfer, an investigator in the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Md.

One patient who, despite having undergone 10 prior therapies -- including 3 rituximab-based chemotherapy regimens -- continued to have lymphoma involvement of the liver and other abdominal areas, remains in complete remission 9 months after treatment with a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19, Dr. Kochenderfer said at the American Society of Hematology annual meeting.

"We’ve chosen to focus on the aggressive large-cell lymphomas, because patients with these lymphomas, such as diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma, have a very poor prognosis if they are refractory to chemotherapy," he said in a briefing prior to his presentation of the results in oral session.

Commenting on the CAR-T cell strategy, Dr. Laurence Cooper of the University of Texas MD Anderson Cancer Center in Houston, who moderated the briefing, noted that "these patients were mortally wounded – they were all going to die, except that these types of engineered T-cell therapies rescued the patients."

The NCI investigators genetically modify each patient’s T-cells in vitro, using a gammaretroviral vector to induce in the cells expression of an anti-CD19 antibody. The process takes 10 days, during which time the patients receive cyclophosphamide and fludarabine to deplete their endogenous leukocytes.

"There’s extensive evidence in multiple animal models and also in humans that shows that depletion of endogenous lymphocytes dramatically enhances the activity of adoptively transferred T-cells. In mouse models, it’s absolutely critical for effectiveness of these CAR T-cells," Dr. Kochenderfer said.

The patients are then infused with the anti-C19-CAR transduced T-cells.

The investigators thus far have treated 15 patients with the technique, including, as noted before, 9 with chemo-refractory large cell lymphomas.

Treatment toxicities included hypotension and neurological toxicities such as confusion, delirium, and transient aphasia.

"Another thing about this therapy that’s amazing is that the patients do become sick; we previously published that the toxicity correlates with serum cytokine levels. [However] they recover very quickly: they can go from being incredibly ill to completely feeling almost normal within 2 days," Dr. Kochenderfer noted.

He and his colleagues also have used the technique in 10 patients who had persistent B-cell malignancies or other cancers following allogeneic stem cell transplantation as an alternative to donor lymphocyte infusions, which have shown inconsistent efficacy and are associated with significant risk for morbidity and mortality for graft-versus-host disease (GvHD).

Of 10 patients treated to date, 3 had "substantial regression" of their malignancies, and one patient with chronic lymphoctic leukemia (CLL) is still in complete remission 12 months after treatment. Another CLL patient had tumor lysis syndrome as he experienced regression of CLL in his bone marrow, blood, and lymph nodes. A patient with the notoriously treatment-refractory mantle cell lymphoma had a partial remission.

As in the first study, toxicities were manageable and consisted mainly of fever, hypotension, and B-cell depletion. No patients developed GvHD after infusion of the altered T-cells.

The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.

NEW ORLEANS – A majority of patients with aggressive, treatment-refractory lymphomas had a complete or partial remission after being treated with chemotherapy and T-cells engineered to target the CD-19 receptor, National Cancer Institute investigators reported here.

In a study of 15 patients, 9 of whom had aggressive large-cell lymphomas and 6 of whom had indolent B-cell malignancies, 6 of 13 evaluable patients had a complete remission, 6 had a partial remission, and 1 had stable disease, said Dr. James N. Kochenderfer, an investigator in the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Md.

One patient who, despite having undergone 10 prior therapies -- including 3 rituximab-based chemotherapy regimens -- continued to have lymphoma involvement of the liver and other abdominal areas, remains in complete remission 9 months after treatment with a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19, Dr. Kochenderfer said at the American Society of Hematology annual meeting.

"We’ve chosen to focus on the aggressive large-cell lymphomas, because patients with these lymphomas, such as diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma, have a very poor prognosis if they are refractory to chemotherapy," he said in a briefing prior to his presentation of the results in oral session.

Commenting on the CAR-T cell strategy, Dr. Laurence Cooper of the University of Texas MD Anderson Cancer Center in Houston, who moderated the briefing, noted that "these patients were mortally wounded – they were all going to die, except that these types of engineered T-cell therapies rescued the patients."

The NCI investigators genetically modify each patient’s T-cells in vitro, using a gammaretroviral vector to induce in the cells expression of an anti-CD19 antibody. The process takes 10 days, during which time the patients receive cyclophosphamide and fludarabine to deplete their endogenous leukocytes.

"There’s extensive evidence in multiple animal models and also in humans that shows that depletion of endogenous lymphocytes dramatically enhances the activity of adoptively transferred T-cells. In mouse models, it’s absolutely critical for effectiveness of these CAR T-cells," Dr. Kochenderfer said.

The patients are then infused with the anti-C19-CAR transduced T-cells.

The investigators thus far have treated 15 patients with the technique, including, as noted before, 9 with chemo-refractory large cell lymphomas.

Treatment toxicities included hypotension and neurological toxicities such as confusion, delirium, and transient aphasia.

"Another thing about this therapy that’s amazing is that the patients do become sick; we previously published that the toxicity correlates with serum cytokine levels. [However] they recover very quickly: they can go from being incredibly ill to completely feeling almost normal within 2 days," Dr. Kochenderfer noted.

He and his colleagues also have used the technique in 10 patients who had persistent B-cell malignancies or other cancers following allogeneic stem cell transplantation as an alternative to donor lymphocyte infusions, which have shown inconsistent efficacy and are associated with significant risk for morbidity and mortality for graft-versus-host disease (GvHD).

Of 10 patients treated to date, 3 had "substantial regression" of their malignancies, and one patient with chronic lymphoctic leukemia (CLL) is still in complete remission 12 months after treatment. Another CLL patient had tumor lysis syndrome as he experienced regression of CLL in his bone marrow, blood, and lymph nodes. A patient with the notoriously treatment-refractory mantle cell lymphoma had a partial remission.

As in the first study, toxicities were manageable and consisted mainly of fever, hypotension, and B-cell depletion. No patients developed GvHD after infusion of the altered T-cells.

The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.

NEW ORLEANS – A majority of patients with aggressive, treatment-refractory lymphomas had a complete or partial remission after being treated with chemotherapy and T-cells engineered to target the CD-19 receptor, National Cancer Institute investigators reported here.

In a study of 15 patients, 9 of whom had aggressive large-cell lymphomas and 6 of whom had indolent B-cell malignancies, 6 of 13 evaluable patients had a complete remission, 6 had a partial remission, and 1 had stable disease, said Dr. James N. Kochenderfer, an investigator in the Experimental Transplantation and Immunology Branch at the National Cancer Institute in Bethesda, Md.

One patient who, despite having undergone 10 prior therapies -- including 3 rituximab-based chemotherapy regimens -- continued to have lymphoma involvement of the liver and other abdominal areas, remains in complete remission 9 months after treatment with a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19, Dr. Kochenderfer said at the American Society of Hematology annual meeting.

"We’ve chosen to focus on the aggressive large-cell lymphomas, because patients with these lymphomas, such as diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma, have a very poor prognosis if they are refractory to chemotherapy," he said in a briefing prior to his presentation of the results in oral session.

Commenting on the CAR-T cell strategy, Dr. Laurence Cooper of the University of Texas MD Anderson Cancer Center in Houston, who moderated the briefing, noted that "these patients were mortally wounded – they were all going to die, except that these types of engineered T-cell therapies rescued the patients."

The NCI investigators genetically modify each patient’s T-cells in vitro, using a gammaretroviral vector to induce in the cells expression of an anti-CD19 antibody. The process takes 10 days, during which time the patients receive cyclophosphamide and fludarabine to deplete their endogenous leukocytes.

"There’s extensive evidence in multiple animal models and also in humans that shows that depletion of endogenous lymphocytes dramatically enhances the activity of adoptively transferred T-cells. In mouse models, it’s absolutely critical for effectiveness of these CAR T-cells," Dr. Kochenderfer said.

The patients are then infused with the anti-C19-CAR transduced T-cells.

The investigators thus far have treated 15 patients with the technique, including, as noted before, 9 with chemo-refractory large cell lymphomas.

Treatment toxicities included hypotension and neurological toxicities such as confusion, delirium, and transient aphasia.

"Another thing about this therapy that’s amazing is that the patients do become sick; we previously published that the toxicity correlates with serum cytokine levels. [However] they recover very quickly: they can go from being incredibly ill to completely feeling almost normal within 2 days," Dr. Kochenderfer noted.

He and his colleagues also have used the technique in 10 patients who had persistent B-cell malignancies or other cancers following allogeneic stem cell transplantation as an alternative to donor lymphocyte infusions, which have shown inconsistent efficacy and are associated with significant risk for morbidity and mortality for graft-versus-host disease (GvHD).

Of 10 patients treated to date, 3 had "substantial regression" of their malignancies, and one patient with chronic lymphoctic leukemia (CLL) is still in complete remission 12 months after treatment. Another CLL patient had tumor lysis syndrome as he experienced regression of CLL in his bone marrow, blood, and lymph nodes. A patient with the notoriously treatment-refractory mantle cell lymphoma had a partial remission.

As in the first study, toxicities were manageable and consisted mainly of fever, hypotension, and B-cell depletion. No patients developed GvHD after infusion of the altered T-cells.

The study was funded by the National Cancer Institute and by Kite Pharma. Dr. Kochenderfer and Dr. Cooper reported having no conflicts of interest to disclose.

Endobronchial ultrasound–guided biopsies made after an electrocautery incision to the lymph node improved biopsy yields from 39% to 71% in 38 nodes, according to a small study presented at the annual meeting of the American College of Chest Physicians meeting.

"Because it is not always possible to pass biopsy forceps through defects in the lymph node – the literature indicates a failure rate of between 10% and 29% – we developed a novel technique," said presenter Dr. Kyle Bramley of Yale University, New Haven, Conn.

The technique employs EBUS, and involves passing an electrocautery knife activated at 40 W through the working channel of the scope in order to make an incision in the bronchial wall and enlarge the defect in the lymph node. This facilitates passage of the forceps into the node so that a larger biopsy sample can be obtained.

To test their technique, Dr. Bramley and his colleagues designed a prospective observational cohort study at a single tertiary academic medical center. Twenty patients (mean age, 68 years), including 11 women, who were undergoing EBUS were enrolled. An associated lung mass was present in 14 (70%) of the participants; 6 (30%) had isolated lymphadenopathy. One patient had prior lymphoma, and two others had prior lung cancer.

The researchers evaluated 68 nodes in all; 19 patients had nodes greater than 9 mm. Cautery was only used when initial attempts failed to biopsy nodes 9 mm or larger using EBUS-guided miniforceps of 1.2 mm.

The average node size biopsied using EBUS-transbronchial needle aspiration (EBUS-TBNA) was 5.7 mm. The average forceps-biopsied node was 15.8 mm.

In all, 23 nodes were biopsied successfully on the first pass using EBUS-TBNA only. The biopsies yielded diagnostic material such as lymphocytes, malignancy, or granulomas in 15 of these nodes.

Of the 15 nodes that required cautery, 12 yielded diagnostic material, and 3 had no diagnostic material.

The overall yield increased from 39% (15 out of 38) without cautery to 71% (27 out of 38) when cautery was used.

Notably, four patients had clinically relevant discrepancies between their cytologies and histopathologies. "In all four, TBNA provided a definitive diagnosis," said Dr. Bramley. "The forceps provided fibroconnective tissue or necrotic debris."

These results did not negate the efficacy of the cautery technique, according to Dr. Bramley. "We think we had a forceps issue ... the 1.2 mm are flexible, but they were unable to push all the way through a tough lymph node capsule."

Dr. Bramley also said that other factors, including the operator learning curve, the smaller size of the nodes the investigators attempted to biopsy, and the "nonideal" population they were studying, contributed to these results.

He and his colleagues have since adjusted the procedure to make cauterization routine and to include a 1.9-mm transbronchial biopsy forceps needle, "which, incidentally, is a lot less expensive than the larger forceps we’d been using," he said.

Although more study is needed, Dr. Bramley said he and his team believed that this technique would be appropriate for future use in isolated mediastinal lymphadenopathy, especially with a low suspicion of non–small cell lung carcinoma; evaluation of lymphoma; and clinical trials requiring core biopsy.

Dr. Bramley had no relevant disclosures.

[email protected]

Endobronchial ultrasound–guided biopsies made after an electrocautery incision to the lymph node improved biopsy yields from 39% to 71% in 38 nodes, according to a small study presented at the annual meeting of the American College of Chest Physicians meeting.

"Because it is not always possible to pass biopsy forceps through defects in the lymph node – the literature indicates a failure rate of between 10% and 29% – we developed a novel technique," said presenter Dr. Kyle Bramley of Yale University, New Haven, Conn.

The technique employs EBUS, and involves passing an electrocautery knife activated at 40 W through the working channel of the scope in order to make an incision in the bronchial wall and enlarge the defect in the lymph node. This facilitates passage of the forceps into the node so that a larger biopsy sample can be obtained.

To test their technique, Dr. Bramley and his colleagues designed a prospective observational cohort study at a single tertiary academic medical center. Twenty patients (mean age, 68 years), including 11 women, who were undergoing EBUS were enrolled. An associated lung mass was present in 14 (70%) of the participants; 6 (30%) had isolated lymphadenopathy. One patient had prior lymphoma, and two others had prior lung cancer.

The researchers evaluated 68 nodes in all; 19 patients had nodes greater than 9 mm. Cautery was only used when initial attempts failed to biopsy nodes 9 mm or larger using EBUS-guided miniforceps of 1.2 mm.

The average node size biopsied using EBUS-transbronchial needle aspiration (EBUS-TBNA) was 5.7 mm. The average forceps-biopsied node was 15.8 mm.

In all, 23 nodes were biopsied successfully on the first pass using EBUS-TBNA only. The biopsies yielded diagnostic material such as lymphocytes, malignancy, or granulomas in 15 of these nodes.

Of the 15 nodes that required cautery, 12 yielded diagnostic material, and 3 had no diagnostic material.

The overall yield increased from 39% (15 out of 38) without cautery to 71% (27 out of 38) when cautery was used.

Notably, four patients had clinically relevant discrepancies between their cytologies and histopathologies. "In all four, TBNA provided a definitive diagnosis," said Dr. Bramley. "The forceps provided fibroconnective tissue or necrotic debris."

These results did not negate the efficacy of the cautery technique, according to Dr. Bramley. "We think we had a forceps issue ... the 1.2 mm are flexible, but they were unable to push all the way through a tough lymph node capsule."

Dr. Bramley also said that other factors, including the operator learning curve, the smaller size of the nodes the investigators attempted to biopsy, and the "nonideal" population they were studying, contributed to these results.

He and his colleagues have since adjusted the procedure to make cauterization routine and to include a 1.9-mm transbronchial biopsy forceps needle, "which, incidentally, is a lot less expensive than the larger forceps we’d been using," he said.

Although more study is needed, Dr. Bramley said he and his team believed that this technique would be appropriate for future use in isolated mediastinal lymphadenopathy, especially with a low suspicion of non–small cell lung carcinoma; evaluation of lymphoma; and clinical trials requiring core biopsy.

Dr. Bramley had no relevant disclosures.

[email protected]

Endobronchial ultrasound–guided biopsies made after an electrocautery incision to the lymph node improved biopsy yields from 39% to 71% in 38 nodes, according to a small study presented at the annual meeting of the American College of Chest Physicians meeting.

"Because it is not always possible to pass biopsy forceps through defects in the lymph node – the literature indicates a failure rate of between 10% and 29% – we developed a novel technique," said presenter Dr. Kyle Bramley of Yale University, New Haven, Conn.

The technique employs EBUS, and involves passing an electrocautery knife activated at 40 W through the working channel of the scope in order to make an incision in the bronchial wall and enlarge the defect in the lymph node. This facilitates passage of the forceps into the node so that a larger biopsy sample can be obtained.

To test their technique, Dr. Bramley and his colleagues designed a prospective observational cohort study at a single tertiary academic medical center. Twenty patients (mean age, 68 years), including 11 women, who were undergoing EBUS were enrolled. An associated lung mass was present in 14 (70%) of the participants; 6 (30%) had isolated lymphadenopathy. One patient had prior lymphoma, and two others had prior lung cancer.

The researchers evaluated 68 nodes in all; 19 patients had nodes greater than 9 mm. Cautery was only used when initial attempts failed to biopsy nodes 9 mm or larger using EBUS-guided miniforceps of 1.2 mm.

The average node size biopsied using EBUS-transbronchial needle aspiration (EBUS-TBNA) was 5.7 mm. The average forceps-biopsied node was 15.8 mm.

In all, 23 nodes were biopsied successfully on the first pass using EBUS-TBNA only. The biopsies yielded diagnostic material such as lymphocytes, malignancy, or granulomas in 15 of these nodes.

Of the 15 nodes that required cautery, 12 yielded diagnostic material, and 3 had no diagnostic material.

The overall yield increased from 39% (15 out of 38) without cautery to 71% (27 out of 38) when cautery was used.

Notably, four patients had clinically relevant discrepancies between their cytologies and histopathologies. "In all four, TBNA provided a definitive diagnosis," said Dr. Bramley. "The forceps provided fibroconnective tissue or necrotic debris."

These results did not negate the efficacy of the cautery technique, according to Dr. Bramley. "We think we had a forceps issue ... the 1.2 mm are flexible, but they were unable to push all the way through a tough lymph node capsule."

Dr. Bramley also said that other factors, including the operator learning curve, the smaller size of the nodes the investigators attempted to biopsy, and the "nonideal" population they were studying, contributed to these results.

He and his colleagues have since adjusted the procedure to make cauterization routine and to include a 1.9-mm transbronchial biopsy forceps needle, "which, incidentally, is a lot less expensive than the larger forceps we’d been using," he said.

Although more study is needed, Dr. Bramley said he and his team believed that this technique would be appropriate for future use in isolated mediastinal lymphadenopathy, especially with a low suspicion of non–small cell lung carcinoma; evaluation of lymphoma; and clinical trials requiring core biopsy.

Dr. Bramley had no relevant disclosures.

[email protected]

Two low-intensity chemotherapy regimens proved effective against Burkitt’s lymphoma and markedly less toxic than existing treatments, according to a report published online Nov. 13 in the New England Journal of Medicine.

In a prospective study, 30 consecutive patients with untreated Burkitt’s lymphoma were enrolled over a 10-year period in one of two low-intensity regimens; both included etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R). A complete remission was achieved in every patient and was sustained for a median of 73-86 months of follow-up, said Dr. Kieron M. Dunleavy of the National Cancer Institute and his associates.

"Low-intensity EPOCH-R–based therapy appears to obviate the need for high-intensity treatment and markedly reduces treatment toxicity while achieving high rates of durable response. Two confirmatory trials [of these regimens] are [now] under way in adults (NCT01092182) and children (NCT01760226)," they noted.

Until now, high-dose methotrexate and cytarabine were considered essential for control of this rare and typically aggressive cancer. "It is accepted that the high growth fraction and short doubling time of Burkitt’s lymphoma make intensive short-course chemotherapy a therapeutic necessity," albeit one that causes severe adverse effects and long-term morbidity. These study findings demonstrate that other less toxic approaches can be at least as effective, Dr. Dunleavy and his colleagues said.

The researchers undertook this study (NCT00001337 and NCT00006436) after hypothesizing that "the exquisite sensitivity of Burkitt’s lymphoma cells to genotoxic stress makes prolonged exposure time, not increased dose, the important therapeutic strategy for maximizing the killing of tumor cells." To test the idea, they studied 17 patients who had the sporadic variant of the malignancy and 13 who had the immunodeficiency-associated variant. Patients were aged 15-88 years, with a median age of 33.

Ten percent of the study population had high-risk disease, 17% had low-risk disease, and 73% had intermediate-risk disease.

The 19 patients who were HIV negative received a standard dose-adjusted EPOCH-R regimen. The 11 HIV-positive patients received a short-course regimen to reduce toxicity even further and got a double-dose of rituximab. The median cumulative dose of doxorubicin-etoposide was 47% lower and that of cyclophosphamide was 57% lower in the latter group.

All patients also were given filgrastim, beginning after the final dose of chemotherapy and continuing until absolute neutrophil recovery.

The HIV-negative group was followed for a median of 86 months and the HIV-positive group for a median of 73 months. At median follow-up, the HIV-negative group had a 95% rate of freedom from disease progression and an overall survival of 100%; the HIV-positive group had a 100% rate of freedom from disease progression and an overall survival of 90%.

Even though the latter group had more advanced Burkitt’s lymphoma as well as immunodeficiency, "they all had complete remissions that have been sustained without additional therapy," Dr. Dunleavy and his associates wrote (N. Engl. J. Med. 2013 Nov. 13 [doi:10.1056/NEJMoa1308392]).

At the most recent follow-up, none of the patients in either group had a disease recurrence or had died from Burkitt’s lymphoma. One HIV-positive patient died of acute myeloid leukemia nearly 3 years after completing the EPOCH-R regimen; it is not yet known whether the chemotherapy may have contributed to the later development of the leukemia, but HIV is a known risk factor for AML, the researchers noted.

There were no treatment-related deaths, and the toxic effects of both low-dose regimens were generally mild. Thrombocytopenia occurred in only 2% of the chemotherapy cycles; fever and neutropenia occurred in 22%. Almost all the chemotherapy infusions were outpatient, with hospital admission from fever and neutropenia occurring in 10% of cycles and only in HIV-positive patients.

This study was funded by the National Cancer Institute. Amgen provides filgrastim to NCI but had no other role in the study. No financial conflicts of interest were reported.

Two low-intensity chemotherapy regimens proved effective against Burkitt’s lymphoma and markedly less toxic than existing treatments, according to a report published online Nov. 13 in the New England Journal of Medicine.

In a prospective study, 30 consecutive patients with untreated Burkitt’s lymphoma were enrolled over a 10-year period in one of two low-intensity regimens; both included etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R). A complete remission was achieved in every patient and was sustained for a median of 73-86 months of follow-up, said Dr. Kieron M. Dunleavy of the National Cancer Institute and his associates.

"Low-intensity EPOCH-R–based therapy appears to obviate the need for high-intensity treatment and markedly reduces treatment toxicity while achieving high rates of durable response. Two confirmatory trials [of these regimens] are [now] under way in adults (NCT01092182) and children (NCT01760226)," they noted.

Until now, high-dose methotrexate and cytarabine were considered essential for control of this rare and typically aggressive cancer. "It is accepted that the high growth fraction and short doubling time of Burkitt’s lymphoma make intensive short-course chemotherapy a therapeutic necessity," albeit one that causes severe adverse effects and long-term morbidity. These study findings demonstrate that other less toxic approaches can be at least as effective, Dr. Dunleavy and his colleagues said.

The researchers undertook this study (NCT00001337 and NCT00006436) after hypothesizing that "the exquisite sensitivity of Burkitt’s lymphoma cells to genotoxic stress makes prolonged exposure time, not increased dose, the important therapeutic strategy for maximizing the killing of tumor cells." To test the idea, they studied 17 patients who had the sporadic variant of the malignancy and 13 who had the immunodeficiency-associated variant. Patients were aged 15-88 years, with a median age of 33.

Ten percent of the study population had high-risk disease, 17% had low-risk disease, and 73% had intermediate-risk disease.

The 19 patients who were HIV negative received a standard dose-adjusted EPOCH-R regimen. The 11 HIV-positive patients received a short-course regimen to reduce toxicity even further and got a double-dose of rituximab. The median cumulative dose of doxorubicin-etoposide was 47% lower and that of cyclophosphamide was 57% lower in the latter group.

All patients also were given filgrastim, beginning after the final dose of chemotherapy and continuing until absolute neutrophil recovery.

The HIV-negative group was followed for a median of 86 months and the HIV-positive group for a median of 73 months. At median follow-up, the HIV-negative group had a 95% rate of freedom from disease progression and an overall survival of 100%; the HIV-positive group had a 100% rate of freedom from disease progression and an overall survival of 90%.

Even though the latter group had more advanced Burkitt’s lymphoma as well as immunodeficiency, "they all had complete remissions that have been sustained without additional therapy," Dr. Dunleavy and his associates wrote (N. Engl. J. Med. 2013 Nov. 13 [doi:10.1056/NEJMoa1308392]).

At the most recent follow-up, none of the patients in either group had a disease recurrence or had died from Burkitt’s lymphoma. One HIV-positive patient died of acute myeloid leukemia nearly 3 years after completing the EPOCH-R regimen; it is not yet known whether the chemotherapy may have contributed to the later development of the leukemia, but HIV is a known risk factor for AML, the researchers noted.

There were no treatment-related deaths, and the toxic effects of both low-dose regimens were generally mild. Thrombocytopenia occurred in only 2% of the chemotherapy cycles; fever and neutropenia occurred in 22%. Almost all the chemotherapy infusions were outpatient, with hospital admission from fever and neutropenia occurring in 10% of cycles and only in HIV-positive patients.

This study was funded by the National Cancer Institute. Amgen provides filgrastim to NCI but had no other role in the study. No financial conflicts of interest were reported.

Two low-intensity chemotherapy regimens proved effective against Burkitt’s lymphoma and markedly less toxic than existing treatments, according to a report published online Nov. 13 in the New England Journal of Medicine.

In a prospective study, 30 consecutive patients with untreated Burkitt’s lymphoma were enrolled over a 10-year period in one of two low-intensity regimens; both included etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R). A complete remission was achieved in every patient and was sustained for a median of 73-86 months of follow-up, said Dr. Kieron M. Dunleavy of the National Cancer Institute and his associates.

"Low-intensity EPOCH-R–based therapy appears to obviate the need for high-intensity treatment and markedly reduces treatment toxicity while achieving high rates of durable response. Two confirmatory trials [of these regimens] are [now] under way in adults (NCT01092182) and children (NCT01760226)," they noted.

Until now, high-dose methotrexate and cytarabine were considered essential for control of this rare and typically aggressive cancer. "It is accepted that the high growth fraction and short doubling time of Burkitt’s lymphoma make intensive short-course chemotherapy a therapeutic necessity," albeit one that causes severe adverse effects and long-term morbidity. These study findings demonstrate that other less toxic approaches can be at least as effective, Dr. Dunleavy and his colleagues said.

The researchers undertook this study (NCT00001337 and NCT00006436) after hypothesizing that "the exquisite sensitivity of Burkitt’s lymphoma cells to genotoxic stress makes prolonged exposure time, not increased dose, the important therapeutic strategy for maximizing the killing of tumor cells." To test the idea, they studied 17 patients who had the sporadic variant of the malignancy and 13 who had the immunodeficiency-associated variant. Patients were aged 15-88 years, with a median age of 33.

Ten percent of the study population had high-risk disease, 17% had low-risk disease, and 73% had intermediate-risk disease.

The 19 patients who were HIV negative received a standard dose-adjusted EPOCH-R regimen. The 11 HIV-positive patients received a short-course regimen to reduce toxicity even further and got a double-dose of rituximab. The median cumulative dose of doxorubicin-etoposide was 47% lower and that of cyclophosphamide was 57% lower in the latter group.

All patients also were given filgrastim, beginning after the final dose of chemotherapy and continuing until absolute neutrophil recovery.

The HIV-negative group was followed for a median of 86 months and the HIV-positive group for a median of 73 months. At median follow-up, the HIV-negative group had a 95% rate of freedom from disease progression and an overall survival of 100%; the HIV-positive group had a 100% rate of freedom from disease progression and an overall survival of 90%.

Even though the latter group had more advanced Burkitt’s lymphoma as well as immunodeficiency, "they all had complete remissions that have been sustained without additional therapy," Dr. Dunleavy and his associates wrote (N. Engl. J. Med. 2013 Nov. 13 [doi:10.1056/NEJMoa1308392]).

At the most recent follow-up, none of the patients in either group had a disease recurrence or had died from Burkitt’s lymphoma. One HIV-positive patient died of acute myeloid leukemia nearly 3 years after completing the EPOCH-R regimen; it is not yet known whether the chemotherapy may have contributed to the later development of the leukemia, but HIV is a known risk factor for AML, the researchers noted.

There were no treatment-related deaths, and the toxic effects of both low-dose regimens were generally mild. Thrombocytopenia occurred in only 2% of the chemotherapy cycles; fever and neutropenia occurred in 22%. Almost all the chemotherapy infusions were outpatient, with hospital admission from fever and neutropenia occurring in 10% of cycles and only in HIV-positive patients.

This study was funded by the National Cancer Institute. Amgen provides filgrastim to NCI but had no other role in the study. No financial conflicts of interest were reported.

Autologous stem cell transplantation was associated with a significant survival benefit at 2 years, compared with induction therapy alone, in a subset of patients with high-risk non-Hodgkin’s lymphoma, based on results from a 40-site study conducted by the Southwest Oncology Group.

In the high-risk subgroup, the 2-year survival rate was 82% in the transplant group and 64% in the induction therapy only group (P = .01). The finding was not part of the preplanned analysis of the SWOG 9704 trial, however. The study was not powered to address the question, so the results must be cautiously interpreted, Dr. Patrick J. Stiff and his colleagues wrote in the study published Oct. 31 (N. Engl. J. Med .2013;369;1681-90).

"The finding needs to be verified prospectively, although undertaking such a trial would be difficult, given the small fraction of patients presenting with high-risk disease," wrote Dr. Stiff of Loyola University, Maywood, Ill., and his coauthors. "However, our analysis ... compares favorably to the 50% progression-free survival rate seen after treatment with (induction therapy) alone, suggesting that early transplantation may be warranted in high-risk disease."

In the overall results of the study, however, patients with aggressive non-Hodgkin’s lymphoma experienced short-term benefits from autologous stem cell transplantation, but their long-term survival was similar to that of patients who had additional cycles of induction therapy.

By the median follow-up of 6 years, the estimated overall survival rate for the two groups was not statistically different at 74% and 71%, respectively. The multivariate analysis found a nonsignificant 26% increase in the risk of death in the control group (P = .30).

The researchers noted that 29% of the control patients who had a relapse or progression after standard therapy had long-term progression-free survival after salvage therapy that often included transplantation. "Thus, early transplantation and late transplantation achieve roughly equivalent overall survival in the combined risk groups," the researchers said.

In the SWOG 9704 study, 253 induction-eligible patients were randomly assigned to the transplantation group or the control group. Patients were a median of 51 years old at baseline. Most (89%) had B-cell lymphoma; the others had T-cell disease. The majority (63%) had stage IV disease; 31% had stage III disease, and 6% were stage II with bulky disease.

All had responded to five cycles of induction therapy with cyclophosphamide, doxorubicin, vincristine and prednisone with or without rituximab (CHOP and R-CHOP).

The 128 patients in the control group received three more CHOP cycles. The 125 patients in the transplantation group got one more CHOP cycle plus an autologous stem cell transplant.

The primary endpoints were 2-year progression-free and overall survival, with 6-year survival as a secondary endpoint.

Disease progression or death occurred at 2 years in 46 of the 125 patients in the transplantation group and in 68 of the 128 patients in the control group. In a multivariate analysis, the hazard ratio for progression or death in the control group vs. the transplantation group was 1.72 (95% confidence interval [CI], 1.18-2.51; P = 0.005; P = .002 in a one-sided test).

At a median follow-up of 6.3 years, however, 37 of the 125 patients in the transplantation group and 47 of the 128 patients in the control group had died. In a multivariate analysis, the hazard ratio for death in the control group versus the transplantation group was 1.26 (95% CI, 0.82-1.94; P = .30; P = .15 in a one-sided test).

The treatment effect did differ, however, between high risk patients and high-intermediate-risk patients for both progression-free survival (P = .04 for interaction) and overall survival (P = .01 for interaction).

In the subset of 165 high-intermediate risk patients, the 2-year progression-free survival rate was 66% among patients in the transplantation group and 63% among patients in the control group (P =.32). In the subset of 88 high-risk patients, the 2-year progression-free survival rates were 75% and 41%, respectively (P = 0001). The estimated overall survival rates for high-intermediate-risk patients in the transplantation and control groups were 70% and 75%, respectively (P = .48), and those for high-risk patients were 82% and 64% (P = .01).

Treatment-related adverse effects were more common in the transplantation group than the control group. The most common adverse events included infection (50% vs. 13%), gastrointestinal effects (26% vs. 5%), metabolic effects (13% vs. 1%), lung effects (11% vs. 2%), and cardiovascular effects (10% vs. 4%).

Six patients in the transplantation group died from treatment toxicity (lung hemorrhage in three; renal failure in one; infection in one; multiorgan failure in one). In the control group, there were three deaths (cardiovascular toxic effects, infection, and unknown factors.)

Salvage chemotherapy and transplantation may have accounted for the comparable late outcomes, the researchers proposed.

In the control group, 29 of the 62 (47%) patients who relapsed underwent salvage chemotherapy and transplantation, and 11 (38%) of them survived without disease progression. An additional seven patients survived without progression after alternative salvage therapy.

In the transplantation group, 23 of the 28 (82%) patients who relapsed died, most after salvage chemoimmunotherapy failed to induce a second remission. Two of the three patients who had allogeneic stem cell transplantation died from toxic effects.

There were 11 secondary cancers among 10 patients in the control group and 12 among 11 patients in the transplantation group. There were no significant survival differences for patients with high-risk B-cell vs. T-cell disease.

Dr. Stiff reported no financial disclosures. However, 8 of the other 18 authors reported financial associations with multiple drug or medical device companies.

[email protected]

*Correction (11/7/2013): A previous version of this article included a headline incorrectly referring to Hodgkin's lymphoma. It should have read as non-Hodgkin's lymphoma. The headline has been updated.

Autologous stem cell transplantation was associated with a significant survival benefit at 2 years, compared with induction therapy alone, in a subset of patients with high-risk non-Hodgkin’s lymphoma, based on results from a 40-site study conducted by the Southwest Oncology Group.

In the high-risk subgroup, the 2-year survival rate was 82% in the transplant group and 64% in the induction therapy only group (P = .01). The finding was not part of the preplanned analysis of the SWOG 9704 trial, however. The study was not powered to address the question, so the results must be cautiously interpreted, Dr. Patrick J. Stiff and his colleagues wrote in the study published Oct. 31 (N. Engl. J. Med .2013;369;1681-90).

"The finding needs to be verified prospectively, although undertaking such a trial would be difficult, given the small fraction of patients presenting with high-risk disease," wrote Dr. Stiff of Loyola University, Maywood, Ill., and his coauthors. "However, our analysis ... compares favorably to the 50% progression-free survival rate seen after treatment with (induction therapy) alone, suggesting that early transplantation may be warranted in high-risk disease."

In the overall results of the study, however, patients with aggressive non-Hodgkin’s lymphoma experienced short-term benefits from autologous stem cell transplantation, but their long-term survival was similar to that of patients who had additional cycles of induction therapy.

By the median follow-up of 6 years, the estimated overall survival rate for the two groups was not statistically different at 74% and 71%, respectively. The multivariate analysis found a nonsignificant 26% increase in the risk of death in the control group (P = .30).

The researchers noted that 29% of the control patients who had a relapse or progression after standard therapy had long-term progression-free survival after salvage therapy that often included transplantation. "Thus, early transplantation and late transplantation achieve roughly equivalent overall survival in the combined risk groups," the researchers said.

In the SWOG 9704 study, 253 induction-eligible patients were randomly assigned to the transplantation group or the control group. Patients were a median of 51 years old at baseline. Most (89%) had B-cell lymphoma; the others had T-cell disease. The majority (63%) had stage IV disease; 31% had stage III disease, and 6% were stage II with bulky disease.

All had responded to five cycles of induction therapy with cyclophosphamide, doxorubicin, vincristine and prednisone with or without rituximab (CHOP and R-CHOP).

The 128 patients in the control group received three more CHOP cycles. The 125 patients in the transplantation group got one more CHOP cycle plus an autologous stem cell transplant.

The primary endpoints were 2-year progression-free and overall survival, with 6-year survival as a secondary endpoint.

Disease progression or death occurred at 2 years in 46 of the 125 patients in the transplantation group and in 68 of the 128 patients in the control group. In a multivariate analysis, the hazard ratio for progression or death in the control group vs. the transplantation group was 1.72 (95% confidence interval [CI], 1.18-2.51; P = 0.005; P = .002 in a one-sided test).

At a median follow-up of 6.3 years, however, 37 of the 125 patients in the transplantation group and 47 of the 128 patients in the control group had died. In a multivariate analysis, the hazard ratio for death in the control group versus the transplantation group was 1.26 (95% CI, 0.82-1.94; P = .30; P = .15 in a one-sided test).

The treatment effect did differ, however, between high risk patients and high-intermediate-risk patients for both progression-free survival (P = .04 for interaction) and overall survival (P = .01 for interaction).

In the subset of 165 high-intermediate risk patients, the 2-year progression-free survival rate was 66% among patients in the transplantation group and 63% among patients in the control group (P =.32). In the subset of 88 high-risk patients, the 2-year progression-free survival rates were 75% and 41%, respectively (P = 0001). The estimated overall survival rates for high-intermediate-risk patients in the transplantation and control groups were 70% and 75%, respectively (P = .48), and those for high-risk patients were 82% and 64% (P = .01).

Treatment-related adverse effects were more common in the transplantation group than the control group. The most common adverse events included infection (50% vs. 13%), gastrointestinal effects (26% vs. 5%), metabolic effects (13% vs. 1%), lung effects (11% vs. 2%), and cardiovascular effects (10% vs. 4%).

Six patients in the transplantation group died from treatment toxicity (lung hemorrhage in three; renal failure in one; infection in one; multiorgan failure in one). In the control group, there were three deaths (cardiovascular toxic effects, infection, and unknown factors.)

Salvage chemotherapy and transplantation may have accounted for the comparable late outcomes, the researchers proposed.

In the control group, 29 of the 62 (47%) patients who relapsed underwent salvage chemotherapy and transplantation, and 11 (38%) of them survived without disease progression. An additional seven patients survived without progression after alternative salvage therapy.

In the transplantation group, 23 of the 28 (82%) patients who relapsed died, most after salvage chemoimmunotherapy failed to induce a second remission. Two of the three patients who had allogeneic stem cell transplantation died from toxic effects.

There were 11 secondary cancers among 10 patients in the control group and 12 among 11 patients in the transplantation group. There were no significant survival differences for patients with high-risk B-cell vs. T-cell disease.

Dr. Stiff reported no financial disclosures. However, 8 of the other 18 authors reported financial associations with multiple drug or medical device companies.

[email protected]

*Correction (11/7/2013): A previous version of this article included a headline incorrectly referring to Hodgkin's lymphoma. It should have read as non-Hodgkin's lymphoma. The headline has been updated.

Autologous stem cell transplantation was associated with a significant survival benefit at 2 years, compared with induction therapy alone, in a subset of patients with high-risk non-Hodgkin’s lymphoma, based on results from a 40-site study conducted by the Southwest Oncology Group.

In the high-risk subgroup, the 2-year survival rate was 82% in the transplant group and 64% in the induction therapy only group (P = .01). The finding was not part of the preplanned analysis of the SWOG 9704 trial, however. The study was not powered to address the question, so the results must be cautiously interpreted, Dr. Patrick J. Stiff and his colleagues wrote in the study published Oct. 31 (N. Engl. J. Med .2013;369;1681-90).

"The finding needs to be verified prospectively, although undertaking such a trial would be difficult, given the small fraction of patients presenting with high-risk disease," wrote Dr. Stiff of Loyola University, Maywood, Ill., and his coauthors. "However, our analysis ... compares favorably to the 50% progression-free survival rate seen after treatment with (induction therapy) alone, suggesting that early transplantation may be warranted in high-risk disease."

In the overall results of the study, however, patients with aggressive non-Hodgkin’s lymphoma experienced short-term benefits from autologous stem cell transplantation, but their long-term survival was similar to that of patients who had additional cycles of induction therapy.

By the median follow-up of 6 years, the estimated overall survival rate for the two groups was not statistically different at 74% and 71%, respectively. The multivariate analysis found a nonsignificant 26% increase in the risk of death in the control group (P = .30).

The researchers noted that 29% of the control patients who had a relapse or progression after standard therapy had long-term progression-free survival after salvage therapy that often included transplantation. "Thus, early transplantation and late transplantation achieve roughly equivalent overall survival in the combined risk groups," the researchers said.

In the SWOG 9704 study, 253 induction-eligible patients were randomly assigned to the transplantation group or the control group. Patients were a median of 51 years old at baseline. Most (89%) had B-cell lymphoma; the others had T-cell disease. The majority (63%) had stage IV disease; 31% had stage III disease, and 6% were stage II with bulky disease.

All had responded to five cycles of induction therapy with cyclophosphamide, doxorubicin, vincristine and prednisone with or without rituximab (CHOP and R-CHOP).

The 128 patients in the control group received three more CHOP cycles. The 125 patients in the transplantation group got one more CHOP cycle plus an autologous stem cell transplant.

The primary endpoints were 2-year progression-free and overall survival, with 6-year survival as a secondary endpoint.

Disease progression or death occurred at 2 years in 46 of the 125 patients in the transplantation group and in 68 of the 128 patients in the control group. In a multivariate analysis, the hazard ratio for progression or death in the control group vs. the transplantation group was 1.72 (95% confidence interval [CI], 1.18-2.51; P = 0.005; P = .002 in a one-sided test).

At a median follow-up of 6.3 years, however, 37 of the 125 patients in the transplantation group and 47 of the 128 patients in the control group had died. In a multivariate analysis, the hazard ratio for death in the control group versus the transplantation group was 1.26 (95% CI, 0.82-1.94; P = .30; P = .15 in a one-sided test).

The treatment effect did differ, however, between high risk patients and high-intermediate-risk patients for both progression-free survival (P = .04 for interaction) and overall survival (P = .01 for interaction).

In the subset of 165 high-intermediate risk patients, the 2-year progression-free survival rate was 66% among patients in the transplantation group and 63% among patients in the control group (P =.32). In the subset of 88 high-risk patients, the 2-year progression-free survival rates were 75% and 41%, respectively (P = 0001). The estimated overall survival rates for high-intermediate-risk patients in the transplantation and control groups were 70% and 75%, respectively (P = .48), and those for high-risk patients were 82% and 64% (P = .01).

Treatment-related adverse effects were more common in the transplantation group than the control group. The most common adverse events included infection (50% vs. 13%), gastrointestinal effects (26% vs. 5%), metabolic effects (13% vs. 1%), lung effects (11% vs. 2%), and cardiovascular effects (10% vs. 4%).

Six patients in the transplantation group died from treatment toxicity (lung hemorrhage in three; renal failure in one; infection in one; multiorgan failure in one). In the control group, there were three deaths (cardiovascular toxic effects, infection, and unknown factors.)

Salvage chemotherapy and transplantation may have accounted for the comparable late outcomes, the researchers proposed.

In the control group, 29 of the 62 (47%) patients who relapsed underwent salvage chemotherapy and transplantation, and 11 (38%) of them survived without disease progression. An additional seven patients survived without progression after alternative salvage therapy.

In the transplantation group, 23 of the 28 (82%) patients who relapsed died, most after salvage chemoimmunotherapy failed to induce a second remission. Two of the three patients who had allogeneic stem cell transplantation died from toxic effects.

There were 11 secondary cancers among 10 patients in the control group and 12 among 11 patients in the transplantation group. There were no significant survival differences for patients with high-risk B-cell vs. T-cell disease.

Dr. Stiff reported no financial disclosures. However, 8 of the other 18 authors reported financial associations with multiple drug or medical device companies.

[email protected]

*Correction (11/7/2013): A previous version of this article included a headline incorrectly referring to Hodgkin's lymphoma. It should have read as non-Hodgkin's lymphoma. The headline has been updated.

Thymomas are rare tumors involving the anterior mediastinum. Localized thymomas can be surgically resected and have an excellent prognosis, whereas advanced thymomas are treated with induction chemotherapy followed by surgery. We report here the successful use of chemotherapy in a woman with stage IV thymoma with pericardial infiltration and effusion. Our experience suggests that aggressive chemotherapy with a cisplatin- and adriamycin-based regimen can lead to rapid regression of thymoma and significant improvement in symptoms.

*Click on the link to the left for a PDF of the full article.   

Thymomas are rare tumors involving the anterior mediastinum. Localized thymomas can be surgically resected and have an excellent prognosis, whereas advanced thymomas are treated with induction chemotherapy followed by surgery. We report here the successful use of chemotherapy in a woman with stage IV thymoma with pericardial infiltration and effusion. Our experience suggests that aggressive chemotherapy with a cisplatin- and adriamycin-based regimen can lead to rapid regression of thymoma and significant improvement in symptoms.

*Click on the link to the left for a PDF of the full article.   

Thymomas are rare tumors involving the anterior mediastinum. Localized thymomas can be surgically resected and have an excellent prognosis, whereas advanced thymomas are treated with induction chemotherapy followed by surgery. We report here the successful use of chemotherapy in a woman with stage IV thymoma with pericardial infiltration and effusion. Our experience suggests that aggressive chemotherapy with a cisplatin- and adriamycin-based regimen can lead to rapid regression of thymoma and significant improvement in symptoms.

*Click on the link to the left for a PDF of the full article.