Neil Osterweil

SAN DIEGO – Induction therapy with obinutuzumab, a bioengineered CD20 inhibitor, induced a slightly higher overall response rate in induction therapy than did rituximab in patients with relapsed, CD20-positive indolent B-cell non-Hodgkin’s lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

According to independent radiology reviewers who were blinded to treatment type, the overall response rate – a composite of complete responses (CR), CR-unconfirmed (CRu), and partial responses – was 44.6% at the end of induction among 74 patients with follicular lymphoma that was treated with obinutuzumab (Genentech’s GA101), compared with 26.7% of patients on rituximab (Rituxan) (P = .01), said Dr. Laurie H. Sehn, a medical oncologist at the University of British Columbia, Vancouver.

However, the overall response rate (ORR) by trial investigator ratings – the primary end point – showed a trend that was not significant, at 44.6% vs. 33.3% (P = .08). There is currently no difference in progression-free survival, said Dr. Sehn, on behalf of her colleagues in the phase II GAUSS trial, touted at the first head-to-head comparison of the two anti-CD20 antibodies.

Patients with other indolent lymphoma histologies were included in the trial, but Dr. Sehn reported full data on patients with follicular lymphomas only.

Obinutuzumab is considered to be a type II monoclonal antibody, shown in preclinical testing to have better ability than does rituximab to cause cell death and to invoke a cellular immune response, with lower complement-dependent cytotoxicity, Dr, Sehn said at a briefing on Dec. 11 in advance of presentation of the results on Dec. 12, 2011.

"As a single drug, rituximab really has had one of the most significant impacts in outcome in B-cell lymphomas in probably the last several decades, so there’s a real motivation to take it one step further and possibly develop a new anti-CD20 antibody that might work better than rituximab or one that may continue to work when rituximab stops working, so as to further improve outcomes," Dr, Sehn said.

A lymphoma specialist who was not involved in the GAUSS trial commented that despite rituximab’s significant benefits, new treatments still are needed, but whether obinutuzumab or another pretender is heir to rituximab’s throne is still unclear.

"We’ve been waiting for a better rituximab for some period of time. It has certainly been the major advance in the therapy of lymphomas in the last 10 to 12 years. The question is, can we do better? Genentech has made an attempt with obinutuzumab to improve the outcome for these patients who are still rituximab-sensitive," commented Dr. Ephraim P. Hochberg of the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"The results are not overwhelming: there’s certainly a trend toward better progression-free survival, there’s a trend toward a slightly improved response rate, and a trend toward a slightly improved complete response rate, but this doesn’t look to be the home run that we might have hoped for with this patient population," he said.

The GAUSS trial is an ongoing, open-label, phase II study. Patients with relapsed CD20+ NHL who had a prior response lasting at least 6 months to a rituximab-containing regimen were randomly assigned to receive either rituximab 375 mg/m² IV weekly for 4 weeks or obinutuzumab 1 g IV weekly for 4 weeks. At the end of the induction phase, patients were assessed and those without disease progression continued with maintenance therapy on the same drug and dose every 2 months for up to 2 years.

In addition to the primary end point results shown above, they found that the best overall response rates by investigator determination occurred in 66.2% of patients on obinutuzumab (35.1% CR/Cru, and 31.1% partial response), and 64% among those on rituximab (18.7% CR/Cru, and 45.3% PR; P = .39). By independent review, the best ORR was 60.8% with obinutuzumab (27% CR/Cru, 33.8% PR), and 46.7% with rituximab (20% and 26.7%; P = .04).*

There were no differences in progression-survival with 39.2% of patients on obinutuzumab having an event at a median time to event of 17.3 months, compared with 34.7% of patients on rituximab with a median time to event of 17.4 months.

In the obinutuzumab arm, 93% of patients had at least one adverse event vs. 81% in the rituximab arm. There were no adverse events leading to death within 28 months of the last dose of obinutuzumab compared with 2 patients on rituximab. Adverse events leading to withdrawal occurred in 8% and 10%, respectively. The proportion of patients having at least one adverse event in each group was identical, at 14%.

Phase III trials with obinutuzumab are underway.

The study was supported by Roche. Dr. Sehn and three coauthors disclosed consulting and receiving honoraria and/or research funding from Roche/Genentech. Two coauthors are Roche employees. Dr. Hochberg has received consulting fees or research support from the company.

*Correction, 12/15/2011: The best overall response rate by independent review was incorrectly stated for rituximab. This version has been updated.

SAN DIEGO – Induction therapy with obinutuzumab, a bioengineered CD20 inhibitor, induced a slightly higher overall response rate in induction therapy than did rituximab in patients with relapsed, CD20-positive indolent B-cell non-Hodgkin’s lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

According to independent radiology reviewers who were blinded to treatment type, the overall response rate – a composite of complete responses (CR), CR-unconfirmed (CRu), and partial responses – was 44.6% at the end of induction among 74 patients with follicular lymphoma that was treated with obinutuzumab (Genentech’s GA101), compared with 26.7% of patients on rituximab (Rituxan) (P = .01), said Dr. Laurie H. Sehn, a medical oncologist at the University of British Columbia, Vancouver.

However, the overall response rate (ORR) by trial investigator ratings – the primary end point – showed a trend that was not significant, at 44.6% vs. 33.3% (P = .08). There is currently no difference in progression-free survival, said Dr. Sehn, on behalf of her colleagues in the phase II GAUSS trial, touted at the first head-to-head comparison of the two anti-CD20 antibodies.

Patients with other indolent lymphoma histologies were included in the trial, but Dr. Sehn reported full data on patients with follicular lymphomas only.

Obinutuzumab is considered to be a type II monoclonal antibody, shown in preclinical testing to have better ability than does rituximab to cause cell death and to invoke a cellular immune response, with lower complement-dependent cytotoxicity, Dr, Sehn said at a briefing on Dec. 11 in advance of presentation of the results on Dec. 12, 2011.

"As a single drug, rituximab really has had one of the most significant impacts in outcome in B-cell lymphomas in probably the last several decades, so there’s a real motivation to take it one step further and possibly develop a new anti-CD20 antibody that might work better than rituximab or one that may continue to work when rituximab stops working, so as to further improve outcomes," Dr, Sehn said.

A lymphoma specialist who was not involved in the GAUSS trial commented that despite rituximab’s significant benefits, new treatments still are needed, but whether obinutuzumab or another pretender is heir to rituximab’s throne is still unclear.

"We’ve been waiting for a better rituximab for some period of time. It has certainly been the major advance in the therapy of lymphomas in the last 10 to 12 years. The question is, can we do better? Genentech has made an attempt with obinutuzumab to improve the outcome for these patients who are still rituximab-sensitive," commented Dr. Ephraim P. Hochberg of the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"The results are not overwhelming: there’s certainly a trend toward better progression-free survival, there’s a trend toward a slightly improved response rate, and a trend toward a slightly improved complete response rate, but this doesn’t look to be the home run that we might have hoped for with this patient population," he said.

The GAUSS trial is an ongoing, open-label, phase II study. Patients with relapsed CD20+ NHL who had a prior response lasting at least 6 months to a rituximab-containing regimen were randomly assigned to receive either rituximab 375 mg/m² IV weekly for 4 weeks or obinutuzumab 1 g IV weekly for 4 weeks. At the end of the induction phase, patients were assessed and those without disease progression continued with maintenance therapy on the same drug and dose every 2 months for up to 2 years.

In addition to the primary end point results shown above, they found that the best overall response rates by investigator determination occurred in 66.2% of patients on obinutuzumab (35.1% CR/Cru, and 31.1% partial response), and 64% among those on rituximab (18.7% CR/Cru, and 45.3% PR; P = .39). By independent review, the best ORR was 60.8% with obinutuzumab (27% CR/Cru, 33.8% PR), and 46.7% with rituximab (20% and 26.7%; P = .04).*

There were no differences in progression-survival with 39.2% of patients on obinutuzumab having an event at a median time to event of 17.3 months, compared with 34.7% of patients on rituximab with a median time to event of 17.4 months.

In the obinutuzumab arm, 93% of patients had at least one adverse event vs. 81% in the rituximab arm. There were no adverse events leading to death within 28 months of the last dose of obinutuzumab compared with 2 patients on rituximab. Adverse events leading to withdrawal occurred in 8% and 10%, respectively. The proportion of patients having at least one adverse event in each group was identical, at 14%.

Phase III trials with obinutuzumab are underway.

The study was supported by Roche. Dr. Sehn and three coauthors disclosed consulting and receiving honoraria and/or research funding from Roche/Genentech. Two coauthors are Roche employees. Dr. Hochberg has received consulting fees or research support from the company.

*Correction, 12/15/2011: The best overall response rate by independent review was incorrectly stated for rituximab. This version has been updated.

SAN DIEGO – Induction therapy with obinutuzumab, a bioengineered CD20 inhibitor, induced a slightly higher overall response rate in induction therapy than did rituximab in patients with relapsed, CD20-positive indolent B-cell non-Hodgkin’s lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

According to independent radiology reviewers who were blinded to treatment type, the overall response rate – a composite of complete responses (CR), CR-unconfirmed (CRu), and partial responses – was 44.6% at the end of induction among 74 patients with follicular lymphoma that was treated with obinutuzumab (Genentech’s GA101), compared with 26.7% of patients on rituximab (Rituxan) (P = .01), said Dr. Laurie H. Sehn, a medical oncologist at the University of British Columbia, Vancouver.

However, the overall response rate (ORR) by trial investigator ratings – the primary end point – showed a trend that was not significant, at 44.6% vs. 33.3% (P = .08). There is currently no difference in progression-free survival, said Dr. Sehn, on behalf of her colleagues in the phase II GAUSS trial, touted at the first head-to-head comparison of the two anti-CD20 antibodies.

Patients with other indolent lymphoma histologies were included in the trial, but Dr. Sehn reported full data on patients with follicular lymphomas only.

Obinutuzumab is considered to be a type II monoclonal antibody, shown in preclinical testing to have better ability than does rituximab to cause cell death and to invoke a cellular immune response, with lower complement-dependent cytotoxicity, Dr, Sehn said at a briefing on Dec. 11 in advance of presentation of the results on Dec. 12, 2011.

"As a single drug, rituximab really has had one of the most significant impacts in outcome in B-cell lymphomas in probably the last several decades, so there’s a real motivation to take it one step further and possibly develop a new anti-CD20 antibody that might work better than rituximab or one that may continue to work when rituximab stops working, so as to further improve outcomes," Dr, Sehn said.

A lymphoma specialist who was not involved in the GAUSS trial commented that despite rituximab’s significant benefits, new treatments still are needed, but whether obinutuzumab or another pretender is heir to rituximab’s throne is still unclear.

"We’ve been waiting for a better rituximab for some period of time. It has certainly been the major advance in the therapy of lymphomas in the last 10 to 12 years. The question is, can we do better? Genentech has made an attempt with obinutuzumab to improve the outcome for these patients who are still rituximab-sensitive," commented Dr. Ephraim P. Hochberg of the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"The results are not overwhelming: there’s certainly a trend toward better progression-free survival, there’s a trend toward a slightly improved response rate, and a trend toward a slightly improved complete response rate, but this doesn’t look to be the home run that we might have hoped for with this patient population," he said.

The GAUSS trial is an ongoing, open-label, phase II study. Patients with relapsed CD20+ NHL who had a prior response lasting at least 6 months to a rituximab-containing regimen were randomly assigned to receive either rituximab 375 mg/m² IV weekly for 4 weeks or obinutuzumab 1 g IV weekly for 4 weeks. At the end of the induction phase, patients were assessed and those without disease progression continued with maintenance therapy on the same drug and dose every 2 months for up to 2 years.

In addition to the primary end point results shown above, they found that the best overall response rates by investigator determination occurred in 66.2% of patients on obinutuzumab (35.1% CR/Cru, and 31.1% partial response), and 64% among those on rituximab (18.7% CR/Cru, and 45.3% PR; P = .39). By independent review, the best ORR was 60.8% with obinutuzumab (27% CR/Cru, 33.8% PR), and 46.7% with rituximab (20% and 26.7%; P = .04).*

There were no differences in progression-survival with 39.2% of patients on obinutuzumab having an event at a median time to event of 17.3 months, compared with 34.7% of patients on rituximab with a median time to event of 17.4 months.

In the obinutuzumab arm, 93% of patients had at least one adverse event vs. 81% in the rituximab arm. There were no adverse events leading to death within 28 months of the last dose of obinutuzumab compared with 2 patients on rituximab. Adverse events leading to withdrawal occurred in 8% and 10%, respectively. The proportion of patients having at least one adverse event in each group was identical, at 14%.

Phase III trials with obinutuzumab are underway.

The study was supported by Roche. Dr. Sehn and three coauthors disclosed consulting and receiving honoraria and/or research funding from Roche/Genentech. Two coauthors are Roche employees. Dr. Hochberg has received consulting fees or research support from the company.

*Correction, 12/15/2011: The best overall response rate by independent review was incorrectly stated for rituximab. This version has been updated.

SAN DIEGO – Maintain with more rituximab or re-treat? For patients with low tumor burden follicular lymphomas, the answer seems to be that it doesn’t much matter, said investigators at the annual meeting of the American Society of Hematology.

Following 4 weeks of induction with rituximab monotherapy, time to treatment failure (TTTF), the primary end point, was virtually identical between patients randomized to 12 weeks of rituximab (Rituxan) maintenance (3.9 years) or rituximab re-treatment at progression (3.6 years, P = .80) in the E4402 RESORT (Rituximab Extended Schedule or Re-Treatment Trial) study.

One year after randomization, there were no significant differences in patient quality of life or stress burden between the treatment strategies, said Dr. Brad S. Kahl of the University of Wisconsin, Madison, on behalf of coinvestigators a briefing in advance of his presentation of the results at a late-breaking abstracts session on Dec. 13.

For the end point of time to first cytotoxic therapy, however, maintenance was significantly better, with 95% of patients not on chemotherapy at 3 years, compared with 86% for the re-treatment strategy (hazard ratio, 2.5; P = .027).

"Both strategies performed extremely well," Dr. Kahl said.

The re-treatment strategy was less costly: Patients in the maintenance arm received a mean of 15.8 total doses of rituximab, compared with a mean 4.5 doses in the re-treatment arm, Dr. Kahl noted. "To get this very small improvement in time to chemotherapy took roughly 4 times more drug in the maintenance arm," he said,

"Given that there was no difference in time to treatment failure, and given the excellent results with re-treatment or time to first chemotherapy, given a slightly better toxicity profile [with re-treatment], given a lack of a quality-of-life benefit for maintenance, and given the resource utilization strategy, the re-treatment strategy would be our recommended strategy when you\'re administering single-agent rituximab in this patient population," he said.

Maintenance does, however, provide a progression-free survival advantage for patients with high tumor burden follicular lymphoma following induction with a combination immunochemotherapy regimen, as shown in the PRIMA trial, in which 2-years of rituximab maintenance was associated with significantly better progression-free survival compared with observation alone (Lancet 2011;377:42-51 [doi:10.1016/S0140-6736(10)62175-7]).

But some patients with low tumor burden may still be anxious about "doing nothing," and for them maintenance is still an appropriate option, said Dr. Ephraim P. Hochberg from the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"In my practice, the patients who I think are going to be psychologically intolerant of relapse, or for whom relapse is a devastating personal event, those are patients for whom there is a benefit to maintenance rituximab that\'s not measured in this sort of analysis," he said in an interview. Dr. Hochberg was not involved in RESORT.

The RESORT trial enrolled 545 patients with non-Hodgkin’s lymphoma, 384 of whom (71%) had a follicular histology; patients with nonfollicular histologies are being analyzed separately. Among the 384 patients, 274 had a response to induction rituximab, and were then randomized to either re-treatment at progression (134) or to maintenance with rituximab 375 mg/m² every 12 weeks. Each strategy was continued until treatment failure.

Time to treatment failure was defined as progression within 6 months of the last rituximab infusion, no response to re-treatment, initiation of alternative therapy, or inability to complete the protocol therapy. Patients were evaluated every 3 months and had restaging CT scans every 6 months,

Grade 3 or 4 hematologic toxicities were seen in less than 5% of patients, and there were two on-study deaths, one in each treatment arm. Both strategies were "extremely well tolerated with minimal toxicities," Dr. Kahl said. There were more toxicities leading to a failure event in the maintenance arm, however.

"Our analysis so far shows that there is no quality-of-life benefit for the maintenance strategy relative to retreatment," he said.

The E4402 (RESORT) trial was sponsored by the Eastern Cooperative Oncology Group and the National Cancer Institute. Dr. Kahl disclosed being a consultant to Genentech and Roche, comarketer of rituximab. Two of his coauthors also are consultants to the company, and one is an employee. Dr. Hochberg has received consulting fees or research support from the company.

SAN DIEGO – Maintain with more rituximab or re-treat? For patients with low tumor burden follicular lymphomas, the answer seems to be that it doesn’t much matter, said investigators at the annual meeting of the American Society of Hematology.

Following 4 weeks of induction with rituximab monotherapy, time to treatment failure (TTTF), the primary end point, was virtually identical between patients randomized to 12 weeks of rituximab (Rituxan) maintenance (3.9 years) or rituximab re-treatment at progression (3.6 years, P = .80) in the E4402 RESORT (Rituximab Extended Schedule or Re-Treatment Trial) study.

One year after randomization, there were no significant differences in patient quality of life or stress burden between the treatment strategies, said Dr. Brad S. Kahl of the University of Wisconsin, Madison, on behalf of coinvestigators a briefing in advance of his presentation of the results at a late-breaking abstracts session on Dec. 13.

For the end point of time to first cytotoxic therapy, however, maintenance was significantly better, with 95% of patients not on chemotherapy at 3 years, compared with 86% for the re-treatment strategy (hazard ratio, 2.5; P = .027).

"Both strategies performed extremely well," Dr. Kahl said.

The re-treatment strategy was less costly: Patients in the maintenance arm received a mean of 15.8 total doses of rituximab, compared with a mean 4.5 doses in the re-treatment arm, Dr. Kahl noted. "To get this very small improvement in time to chemotherapy took roughly 4 times more drug in the maintenance arm," he said,

"Given that there was no difference in time to treatment failure, and given the excellent results with re-treatment or time to first chemotherapy, given a slightly better toxicity profile [with re-treatment], given a lack of a quality-of-life benefit for maintenance, and given the resource utilization strategy, the re-treatment strategy would be our recommended strategy when you\'re administering single-agent rituximab in this patient population," he said.

Maintenance does, however, provide a progression-free survival advantage for patients with high tumor burden follicular lymphoma following induction with a combination immunochemotherapy regimen, as shown in the PRIMA trial, in which 2-years of rituximab maintenance was associated with significantly better progression-free survival compared with observation alone (Lancet 2011;377:42-51 [doi:10.1016/S0140-6736(10)62175-7]).

But some patients with low tumor burden may still be anxious about "doing nothing," and for them maintenance is still an appropriate option, said Dr. Ephraim P. Hochberg from the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"In my practice, the patients who I think are going to be psychologically intolerant of relapse, or for whom relapse is a devastating personal event, those are patients for whom there is a benefit to maintenance rituximab that\'s not measured in this sort of analysis," he said in an interview. Dr. Hochberg was not involved in RESORT.

The RESORT trial enrolled 545 patients with non-Hodgkin’s lymphoma, 384 of whom (71%) had a follicular histology; patients with nonfollicular histologies are being analyzed separately. Among the 384 patients, 274 had a response to induction rituximab, and were then randomized to either re-treatment at progression (134) or to maintenance with rituximab 375 mg/m² every 12 weeks. Each strategy was continued until treatment failure.

Time to treatment failure was defined as progression within 6 months of the last rituximab infusion, no response to re-treatment, initiation of alternative therapy, or inability to complete the protocol therapy. Patients were evaluated every 3 months and had restaging CT scans every 6 months,

Grade 3 or 4 hematologic toxicities were seen in less than 5% of patients, and there were two on-study deaths, one in each treatment arm. Both strategies were "extremely well tolerated with minimal toxicities," Dr. Kahl said. There were more toxicities leading to a failure event in the maintenance arm, however.

"Our analysis so far shows that there is no quality-of-life benefit for the maintenance strategy relative to retreatment," he said.

The E4402 (RESORT) trial was sponsored by the Eastern Cooperative Oncology Group and the National Cancer Institute. Dr. Kahl disclosed being a consultant to Genentech and Roche, comarketer of rituximab. Two of his coauthors also are consultants to the company, and one is an employee. Dr. Hochberg has received consulting fees or research support from the company.

SAN DIEGO – Maintain with more rituximab or re-treat? For patients with low tumor burden follicular lymphomas, the answer seems to be that it doesn’t much matter, said investigators at the annual meeting of the American Society of Hematology.

Following 4 weeks of induction with rituximab monotherapy, time to treatment failure (TTTF), the primary end point, was virtually identical between patients randomized to 12 weeks of rituximab (Rituxan) maintenance (3.9 years) or rituximab re-treatment at progression (3.6 years, P = .80) in the E4402 RESORT (Rituximab Extended Schedule or Re-Treatment Trial) study.

One year after randomization, there were no significant differences in patient quality of life or stress burden between the treatment strategies, said Dr. Brad S. Kahl of the University of Wisconsin, Madison, on behalf of coinvestigators a briefing in advance of his presentation of the results at a late-breaking abstracts session on Dec. 13.

For the end point of time to first cytotoxic therapy, however, maintenance was significantly better, with 95% of patients not on chemotherapy at 3 years, compared with 86% for the re-treatment strategy (hazard ratio, 2.5; P = .027).

"Both strategies performed extremely well," Dr. Kahl said.

The re-treatment strategy was less costly: Patients in the maintenance arm received a mean of 15.8 total doses of rituximab, compared with a mean 4.5 doses in the re-treatment arm, Dr. Kahl noted. "To get this very small improvement in time to chemotherapy took roughly 4 times more drug in the maintenance arm," he said,

"Given that there was no difference in time to treatment failure, and given the excellent results with re-treatment or time to first chemotherapy, given a slightly better toxicity profile [with re-treatment], given a lack of a quality-of-life benefit for maintenance, and given the resource utilization strategy, the re-treatment strategy would be our recommended strategy when you\'re administering single-agent rituximab in this patient population," he said.

Maintenance does, however, provide a progression-free survival advantage for patients with high tumor burden follicular lymphoma following induction with a combination immunochemotherapy regimen, as shown in the PRIMA trial, in which 2-years of rituximab maintenance was associated with significantly better progression-free survival compared with observation alone (Lancet 2011;377:42-51 [doi:10.1016/S0140-6736(10)62175-7]).

But some patients with low tumor burden may still be anxious about "doing nothing," and for them maintenance is still an appropriate option, said Dr. Ephraim P. Hochberg from the division of hematology/oncology at the Massachusetts General Hospital Cancer Center in Boston.

"In my practice, the patients who I think are going to be psychologically intolerant of relapse, or for whom relapse is a devastating personal event, those are patients for whom there is a benefit to maintenance rituximab that\'s not measured in this sort of analysis," he said in an interview. Dr. Hochberg was not involved in RESORT.

The RESORT trial enrolled 545 patients with non-Hodgkin’s lymphoma, 384 of whom (71%) had a follicular histology; patients with nonfollicular histologies are being analyzed separately. Among the 384 patients, 274 had a response to induction rituximab, and were then randomized to either re-treatment at progression (134) or to maintenance with rituximab 375 mg/m² every 12 weeks. Each strategy was continued until treatment failure.

Time to treatment failure was defined as progression within 6 months of the last rituximab infusion, no response to re-treatment, initiation of alternative therapy, or inability to complete the protocol therapy. Patients were evaluated every 3 months and had restaging CT scans every 6 months,

Grade 3 or 4 hematologic toxicities were seen in less than 5% of patients, and there were two on-study deaths, one in each treatment arm. Both strategies were "extremely well tolerated with minimal toxicities," Dr. Kahl said. There were more toxicities leading to a failure event in the maintenance arm, however.

"Our analysis so far shows that there is no quality-of-life benefit for the maintenance strategy relative to retreatment," he said.

The E4402 (RESORT) trial was sponsored by the Eastern Cooperative Oncology Group and the National Cancer Institute. Dr. Kahl disclosed being a consultant to Genentech and Roche, comarketer of rituximab. Two of his coauthors also are consultants to the company, and one is an employee. Dr. Hochberg has received consulting fees or research support from the company.

SAN DIEGO – A novel targeted agent was associated with high objective response rates at 10 months in patients with relapsed/refractory, heavily pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

At 10.2 months’ median follow-up, objective responses (combined complete and partial responses) were seen in 70% of 27 CLL/SLL patients assigned to a 420-mg daily dose of PCI-32765, an inhibitor of Bruton’s tyrosine kinase (BTK). Objective responses were seen at 6.5 months’ follow-up in 44% of 34 patients on an 840 mg daily dose, reported Dr. Susan O’Brien, professor in the department of leukemia at the University of Texas MD Anderson Cancer Center in Houston.

The researchers had previously reported a 48% objective response rate at 6.2 months median follow-up.

Among patients who did not have a complete or partial response, a nodal partial response was noted in 19% of those in the 420-mg cohort and in 35% of those in the 840-mg group. A nodal partial response was defined as a reduction of greater than 50% in aggregate lymph node size, but with residual lymphocytosis.

Progression-free survival at 6 months is 92% in the 27 patients in the 420-mg cohort, and 90% in the 34 patients in the 840-mg group.

Although it’s still too early to tell which dose will be more effective, the evidence to date suggests that the 420-mg dose completely inhibits activity of the targeted kinase. Thus, the 840-mg dose may not be necessary, Dr. O'Brien said.

Further, PC-32765 does not cause myelosuppression, a trait noted with imatinib (Gleevec) and other tyrosine kinase inhibitors that are effective in other leukemia subtypes.

"This is a big deal in CLL because all of the treatments that we have are pretty much chemo-based or antibody-based treatments. The biggest complication in treating CLL with pretty much every therapy we have is myelosuppression and infection, and of course these people are [already] immune suppressed. To have an agent that’s not myelosuppressive and this effective is very exciting," she said in a briefing prior to her presentation of the results at a session on Tuesday, Dec.13.

A leukemia specialist who was not involved in the study said that the results are particularly impressive given the nature of the patient population.

Patients also tolerated the drug well. The incidence of serious adverse events potentially related to PCI-32765 was 10%. The most common adverse event was diarrhea, which was generally mild, easily controlled, and self-limited, Dr. O’Brien said.

PCI-32765 binds selectively and irreversibly to BTK, an essential element of the B-cell antigen receptor signaling pathway, thereby blocking receptor signaling, inducing cell death via apoptosis, and inhibiting cellular migration and adhesion of malignant B cells.

"To have an agent that’s not myelo-suppressive and this effective is very exciting."

The investigators enrolled both treatment-naive patients with CLL and those who had relapsed/refractory disease following at least two prior therapies, including fludarabine. The patients were treated with PCI-32765 administered daily for 28-day cycles until disease progression. Treatment-naive patients and 27 patients with relapsed/refractory disease were assigned to the 420-mg dose; 34 patients with relapsed/refractory disease were assigned to the 840-mg dose.

In all, 72% of patients had one or more poor-risk molecular features. Of this group, 31% had the 17p deletion, 33% had the 11q deletion, and 57% had IgV_H un-mutated.

Two patients dropped out of the trial because of adverse events (dose group not specified), and six patients (two in the 420-mg group, four in the 840-mg group) required a dose reduction.

The most frequently reported grade 1 or 2 adverse events were diarrhea, fatigue, nausea, and ecchymosis. Serious adverse events were reported in 38% of patients. Serious events potentially related to the drug occurred in 10% of all patients.

The investigators noted that, in a majority of patients "a characteristic pattern of response, with a transient phase of lymphocytosis typically peaking within the first 2 months of therapy, followed by resolution over time."

At last follow-up, 22 of 27 patients on the 420-mg dose and 28 of 34 on the 840-mg dose were still on therapy. Phase-III trials are planned.

The trial was funded by Pharmacyclics. Dr. O’Brien disclosed serving on the board of directors or advisory committee, and has received research funding from the company. All of her coauthors disclosed either receiving research funding or consulting fees from the company, or being employees and receiving equity ownership in Phamacyclics.

SAN DIEGO – A novel targeted agent was associated with high objective response rates at 10 months in patients with relapsed/refractory, heavily pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

At 10.2 months’ median follow-up, objective responses (combined complete and partial responses) were seen in 70% of 27 CLL/SLL patients assigned to a 420-mg daily dose of PCI-32765, an inhibitor of Bruton’s tyrosine kinase (BTK). Objective responses were seen at 6.5 months’ follow-up in 44% of 34 patients on an 840 mg daily dose, reported Dr. Susan O’Brien, professor in the department of leukemia at the University of Texas MD Anderson Cancer Center in Houston.

The researchers had previously reported a 48% objective response rate at 6.2 months median follow-up.

Among patients who did not have a complete or partial response, a nodal partial response was noted in 19% of those in the 420-mg cohort and in 35% of those in the 840-mg group. A nodal partial response was defined as a reduction of greater than 50% in aggregate lymph node size, but with residual lymphocytosis.

Progression-free survival at 6 months is 92% in the 27 patients in the 420-mg cohort, and 90% in the 34 patients in the 840-mg group.

Although it’s still too early to tell which dose will be more effective, the evidence to date suggests that the 420-mg dose completely inhibits activity of the targeted kinase. Thus, the 840-mg dose may not be necessary, Dr. O'Brien said.

Further, PC-32765 does not cause myelosuppression, a trait noted with imatinib (Gleevec) and other tyrosine kinase inhibitors that are effective in other leukemia subtypes.

"This is a big deal in CLL because all of the treatments that we have are pretty much chemo-based or antibody-based treatments. The biggest complication in treating CLL with pretty much every therapy we have is myelosuppression and infection, and of course these people are [already] immune suppressed. To have an agent that’s not myelosuppressive and this effective is very exciting," she said in a briefing prior to her presentation of the results at a session on Tuesday, Dec.13.

A leukemia specialist who was not involved in the study said that the results are particularly impressive given the nature of the patient population.

Patients also tolerated the drug well. The incidence of serious adverse events potentially related to PCI-32765 was 10%. The most common adverse event was diarrhea, which was generally mild, easily controlled, and self-limited, Dr. O’Brien said.

PCI-32765 binds selectively and irreversibly to BTK, an essential element of the B-cell antigen receptor signaling pathway, thereby blocking receptor signaling, inducing cell death via apoptosis, and inhibiting cellular migration and adhesion of malignant B cells.

"To have an agent that’s not myelo-suppressive and this effective is very exciting."

The investigators enrolled both treatment-naive patients with CLL and those who had relapsed/refractory disease following at least two prior therapies, including fludarabine. The patients were treated with PCI-32765 administered daily for 28-day cycles until disease progression. Treatment-naive patients and 27 patients with relapsed/refractory disease were assigned to the 420-mg dose; 34 patients with relapsed/refractory disease were assigned to the 840-mg dose.

In all, 72% of patients had one or more poor-risk molecular features. Of this group, 31% had the 17p deletion, 33% had the 11q deletion, and 57% had IgV_H un-mutated.

Two patients dropped out of the trial because of adverse events (dose group not specified), and six patients (two in the 420-mg group, four in the 840-mg group) required a dose reduction.

The most frequently reported grade 1 or 2 adverse events were diarrhea, fatigue, nausea, and ecchymosis. Serious adverse events were reported in 38% of patients. Serious events potentially related to the drug occurred in 10% of all patients.

The investigators noted that, in a majority of patients "a characteristic pattern of response, with a transient phase of lymphocytosis typically peaking within the first 2 months of therapy, followed by resolution over time."

At last follow-up, 22 of 27 patients on the 420-mg dose and 28 of 34 on the 840-mg dose were still on therapy. Phase-III trials are planned.

The trial was funded by Pharmacyclics. Dr. O’Brien disclosed serving on the board of directors or advisory committee, and has received research funding from the company. All of her coauthors disclosed either receiving research funding or consulting fees from the company, or being employees and receiving equity ownership in Phamacyclics.

SAN DIEGO – A novel targeted agent was associated with high objective response rates at 10 months in patients with relapsed/refractory, heavily pretreated chronic lymphocytic leukemia/small lymphocytic lymphoma, investigators reported at the annual meeting of the American Society of Hematology.

At 10.2 months’ median follow-up, objective responses (combined complete and partial responses) were seen in 70% of 27 CLL/SLL patients assigned to a 420-mg daily dose of PCI-32765, an inhibitor of Bruton’s tyrosine kinase (BTK). Objective responses were seen at 6.5 months’ follow-up in 44% of 34 patients on an 840 mg daily dose, reported Dr. Susan O’Brien, professor in the department of leukemia at the University of Texas MD Anderson Cancer Center in Houston.

The researchers had previously reported a 48% objective response rate at 6.2 months median follow-up.

Among patients who did not have a complete or partial response, a nodal partial response was noted in 19% of those in the 420-mg cohort and in 35% of those in the 840-mg group. A nodal partial response was defined as a reduction of greater than 50% in aggregate lymph node size, but with residual lymphocytosis.

Progression-free survival at 6 months is 92% in the 27 patients in the 420-mg cohort, and 90% in the 34 patients in the 840-mg group.

Although it’s still too early to tell which dose will be more effective, the evidence to date suggests that the 420-mg dose completely inhibits activity of the targeted kinase. Thus, the 840-mg dose may not be necessary, Dr. O'Brien said.

Further, PC-32765 does not cause myelosuppression, a trait noted with imatinib (Gleevec) and other tyrosine kinase inhibitors that are effective in other leukemia subtypes.

"This is a big deal in CLL because all of the treatments that we have are pretty much chemo-based or antibody-based treatments. The biggest complication in treating CLL with pretty much every therapy we have is myelosuppression and infection, and of course these people are [already] immune suppressed. To have an agent that’s not myelosuppressive and this effective is very exciting," she said in a briefing prior to her presentation of the results at a session on Tuesday, Dec.13.

A leukemia specialist who was not involved in the study said that the results are particularly impressive given the nature of the patient population.

Patients also tolerated the drug well. The incidence of serious adverse events potentially related to PCI-32765 was 10%. The most common adverse event was diarrhea, which was generally mild, easily controlled, and self-limited, Dr. O’Brien said.

PCI-32765 binds selectively and irreversibly to BTK, an essential element of the B-cell antigen receptor signaling pathway, thereby blocking receptor signaling, inducing cell death via apoptosis, and inhibiting cellular migration and adhesion of malignant B cells.

"To have an agent that’s not myelo-suppressive and this effective is very exciting."

The investigators enrolled both treatment-naive patients with CLL and those who had relapsed/refractory disease following at least two prior therapies, including fludarabine. The patients were treated with PCI-32765 administered daily for 28-day cycles until disease progression. Treatment-naive patients and 27 patients with relapsed/refractory disease were assigned to the 420-mg dose; 34 patients with relapsed/refractory disease were assigned to the 840-mg dose.

In all, 72% of patients had one or more poor-risk molecular features. Of this group, 31% had the 17p deletion, 33% had the 11q deletion, and 57% had IgV_H un-mutated.

Two patients dropped out of the trial because of adverse events (dose group not specified), and six patients (two in the 420-mg group, four in the 840-mg group) required a dose reduction.

The most frequently reported grade 1 or 2 adverse events were diarrhea, fatigue, nausea, and ecchymosis. Serious adverse events were reported in 38% of patients. Serious events potentially related to the drug occurred in 10% of all patients.

The investigators noted that, in a majority of patients "a characteristic pattern of response, with a transient phase of lymphocytosis typically peaking within the first 2 months of therapy, followed by resolution over time."

At last follow-up, 22 of 27 patients on the 420-mg dose and 28 of 34 on the 840-mg dose were still on therapy. Phase-III trials are planned.

The trial was funded by Pharmacyclics. Dr. O’Brien disclosed serving on the board of directors or advisory committee, and has received research funding from the company. All of her coauthors disclosed either receiving research funding or consulting fees from the company, or being employees and receiving equity ownership in Phamacyclics.

SAN DIEGO – Long after the event, hematopoietic stem cell recipients still bear a heavier burden of physical and emotional problems than do their siblings, and greater use of specialized health care, according to investigators at the annual meeting of the American Society of Hematology.

In all, 74% of transplant survivors reported having a chronic health condition at least 10 years on, compared with 39% of age-matched siblings in the Bone Marrow Transplant Survivor Study.

"The difference was especially prominent for severe or life-threatening conditions: 25% of the survivors versus 8% of the siblings reported having a severe, life threatening condition," said Dr. Can-Lan Sun, director of survey research at City of Hope Medical Center in Duarte, Calif., on behalf of coauthors at a press briefing.

"Survivors were five times more likely to report a severe life-threatening condition than siblings," she added.

The cumulative incidence of chronic health conditions over 15 years of follow-up was 71%, and the cumulative incidence of severe, life-threatening events was 40%, the authors found.

"We have many more survivors than we used to, and we’re very thankful for that, but I think it’s important to realize that once a transplant is over, it’s not really over – and that there are some long-term effects either because of the transplant procedure, or because of the chemotherapy that the patient had to get to the transplant," commented Dr. Stephanie J. Lee, professor of medicine at the University of Washington, and a transplant specialist at the Fred Hutchinson Cancer Research Center, both in Seattle.

Dr. Lee moderated the briefing but was not involved in the study.

The authors conducted a retrospective study that surveyed 366 hematopoietic cell transplantation (HCT) survivors of at least 10 years’ duration and compared outcomes of chronic health conditions and psychological health with those of 309 aged-matched siblings. The severe and/or life-threatening conditions they considered included:

• Impaired hearing (loss not corrected by hearing aids).

• Legal blindness.

• Dialysis support.

• Gastrointestinal problems (surgery for intestinal obstruction, rectal or anal strictures, or cirrhosis.

• Cardiovascular disease (coronary artery disease, congestive heart failure, stroke).

• Joint replacement.

• Diabetes.

• Subsequent cancers.

The majority of survivors (65%) had received allogeneic transplants from a relative, 27% had autologous transplants, and 8% received HCT from unrelated donors. In all, 72% of patients had a conditioning regimen with total body irradiation and cyclophosphamide or etoposide, or both.

Indications for transplant were acute myeloid leukemia (28%), chronic myeloid leukemia (17%), acute lymphocytic leukemia (17%), non-Hodgkin’s lymphoma (11%), Hodgkin’s lymphoma (7%), aplastic anemia, or others (10%).

In an analysis adjusted for age at questionnaire, sex, race/ethnicity, education level attained, income and insurance status, they found that the relative risk (RR) for survivors to have any grade 1-4 condition was 2.16. The RR for having a grade 1 or 2 condition was 2.24, and for having a grade 3 or 4 condition was 5.64 (P less than .001 for all comparisons).

In addition, an analysis of adverse psychological outcomes, adjusted for the same factors, showed that survivors had an RR for somatic distress (unexplained physical symptoms such as pain, fatigue, etc.) of 2.73 (P = .03).

"Among survivors, females, those with low income, and those with poor health status were more likely to report somatic distress," Dr. Sun said.

In contrast, there were no significant differences between survivors and siblings in risk for anxiety, depression, or global distress.

Survivors also reported high use of health care services, with 78% reporting receiving a general physical examination within the past 2 years, and nearly two-thirds reporting that they had returned to the cancer center for ongoing care.

"As HCT continues to be a curative option for a variety of hematological malignancies, the burden of long-term physical and emotional morbidity formed by HCT recipients who have survived at least 10 years is substantial," Dr. Sun concluded.

The study was supported by a National Institutes of Health grant and a Leukemia & Lymphoma Society Scholar award to Dr. Sun. Neither she nor Dr. Lee had reported conflicts of interest.

SAN DIEGO – Long after the event, hematopoietic stem cell recipients still bear a heavier burden of physical and emotional problems than do their siblings, and greater use of specialized health care, according to investigators at the annual meeting of the American Society of Hematology.

In all, 74% of transplant survivors reported having a chronic health condition at least 10 years on, compared with 39% of age-matched siblings in the Bone Marrow Transplant Survivor Study.

"The difference was especially prominent for severe or life-threatening conditions: 25% of the survivors versus 8% of the siblings reported having a severe, life threatening condition," said Dr. Can-Lan Sun, director of survey research at City of Hope Medical Center in Duarte, Calif., on behalf of coauthors at a press briefing.

"Survivors were five times more likely to report a severe life-threatening condition than siblings," she added.

The cumulative incidence of chronic health conditions over 15 years of follow-up was 71%, and the cumulative incidence of severe, life-threatening events was 40%, the authors found.

"We have many more survivors than we used to, and we’re very thankful for that, but I think it’s important to realize that once a transplant is over, it’s not really over – and that there are some long-term effects either because of the transplant procedure, or because of the chemotherapy that the patient had to get to the transplant," commented Dr. Stephanie J. Lee, professor of medicine at the University of Washington, and a transplant specialist at the Fred Hutchinson Cancer Research Center, both in Seattle.

Dr. Lee moderated the briefing but was not involved in the study.

The authors conducted a retrospective study that surveyed 366 hematopoietic cell transplantation (HCT) survivors of at least 10 years’ duration and compared outcomes of chronic health conditions and psychological health with those of 309 aged-matched siblings. The severe and/or life-threatening conditions they considered included:

• Impaired hearing (loss not corrected by hearing aids).

• Legal blindness.

• Dialysis support.

• Gastrointestinal problems (surgery for intestinal obstruction, rectal or anal strictures, or cirrhosis.

• Cardiovascular disease (coronary artery disease, congestive heart failure, stroke).

• Joint replacement.

• Diabetes.

• Subsequent cancers.

The majority of survivors (65%) had received allogeneic transplants from a relative, 27% had autologous transplants, and 8% received HCT from unrelated donors. In all, 72% of patients had a conditioning regimen with total body irradiation and cyclophosphamide or etoposide, or both.

Indications for transplant were acute myeloid leukemia (28%), chronic myeloid leukemia (17%), acute lymphocytic leukemia (17%), non-Hodgkin’s lymphoma (11%), Hodgkin’s lymphoma (7%), aplastic anemia, or others (10%).

In an analysis adjusted for age at questionnaire, sex, race/ethnicity, education level attained, income and insurance status, they found that the relative risk (RR) for survivors to have any grade 1-4 condition was 2.16. The RR for having a grade 1 or 2 condition was 2.24, and for having a grade 3 or 4 condition was 5.64 (P less than .001 for all comparisons).

In addition, an analysis of adverse psychological outcomes, adjusted for the same factors, showed that survivors had an RR for somatic distress (unexplained physical symptoms such as pain, fatigue, etc.) of 2.73 (P = .03).

"Among survivors, females, those with low income, and those with poor health status were more likely to report somatic distress," Dr. Sun said.

In contrast, there were no significant differences between survivors and siblings in risk for anxiety, depression, or global distress.

Survivors also reported high use of health care services, with 78% reporting receiving a general physical examination within the past 2 years, and nearly two-thirds reporting that they had returned to the cancer center for ongoing care.

"As HCT continues to be a curative option for a variety of hematological malignancies, the burden of long-term physical and emotional morbidity formed by HCT recipients who have survived at least 10 years is substantial," Dr. Sun concluded.

The study was supported by a National Institutes of Health grant and a Leukemia & Lymphoma Society Scholar award to Dr. Sun. Neither she nor Dr. Lee had reported conflicts of interest.

SAN DIEGO – Long after the event, hematopoietic stem cell recipients still bear a heavier burden of physical and emotional problems than do their siblings, and greater use of specialized health care, according to investigators at the annual meeting of the American Society of Hematology.

In all, 74% of transplant survivors reported having a chronic health condition at least 10 years on, compared with 39% of age-matched siblings in the Bone Marrow Transplant Survivor Study.

"The difference was especially prominent for severe or life-threatening conditions: 25% of the survivors versus 8% of the siblings reported having a severe, life threatening condition," said Dr. Can-Lan Sun, director of survey research at City of Hope Medical Center in Duarte, Calif., on behalf of coauthors at a press briefing.

"Survivors were five times more likely to report a severe life-threatening condition than siblings," she added.

The cumulative incidence of chronic health conditions over 15 years of follow-up was 71%, and the cumulative incidence of severe, life-threatening events was 40%, the authors found.

"We have many more survivors than we used to, and we’re very thankful for that, but I think it’s important to realize that once a transplant is over, it’s not really over – and that there are some long-term effects either because of the transplant procedure, or because of the chemotherapy that the patient had to get to the transplant," commented Dr. Stephanie J. Lee, professor of medicine at the University of Washington, and a transplant specialist at the Fred Hutchinson Cancer Research Center, both in Seattle.

Dr. Lee moderated the briefing but was not involved in the study.

The authors conducted a retrospective study that surveyed 366 hematopoietic cell transplantation (HCT) survivors of at least 10 years’ duration and compared outcomes of chronic health conditions and psychological health with those of 309 aged-matched siblings. The severe and/or life-threatening conditions they considered included:

• Impaired hearing (loss not corrected by hearing aids).

• Legal blindness.

• Dialysis support.

• Gastrointestinal problems (surgery for intestinal obstruction, rectal or anal strictures, or cirrhosis.

• Cardiovascular disease (coronary artery disease, congestive heart failure, stroke).

• Joint replacement.

• Diabetes.

• Subsequent cancers.

The majority of survivors (65%) had received allogeneic transplants from a relative, 27% had autologous transplants, and 8% received HCT from unrelated donors. In all, 72% of patients had a conditioning regimen with total body irradiation and cyclophosphamide or etoposide, or both.

Indications for transplant were acute myeloid leukemia (28%), chronic myeloid leukemia (17%), acute lymphocytic leukemia (17%), non-Hodgkin’s lymphoma (11%), Hodgkin’s lymphoma (7%), aplastic anemia, or others (10%).

In an analysis adjusted for age at questionnaire, sex, race/ethnicity, education level attained, income and insurance status, they found that the relative risk (RR) for survivors to have any grade 1-4 condition was 2.16. The RR for having a grade 1 or 2 condition was 2.24, and for having a grade 3 or 4 condition was 5.64 (P less than .001 for all comparisons).

In addition, an analysis of adverse psychological outcomes, adjusted for the same factors, showed that survivors had an RR for somatic distress (unexplained physical symptoms such as pain, fatigue, etc.) of 2.73 (P = .03).

"Among survivors, females, those with low income, and those with poor health status were more likely to report somatic distress," Dr. Sun said.

In contrast, there were no significant differences between survivors and siblings in risk for anxiety, depression, or global distress.

Survivors also reported high use of health care services, with 78% reporting receiving a general physical examination within the past 2 years, and nearly two-thirds reporting that they had returned to the cancer center for ongoing care.

"As HCT continues to be a curative option for a variety of hematological malignancies, the burden of long-term physical and emotional morbidity formed by HCT recipients who have survived at least 10 years is substantial," Dr. Sun concluded.

The study was supported by a National Institutes of Health grant and a Leukemia & Lymphoma Society Scholar award to Dr. Sun. Neither she nor Dr. Lee had reported conflicts of interest.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.