ASH Hematologic Malignancies

CHICAGO – Subcutaneous and intravenous bortezomib performed comparably well in patients with newly diagnosed multiple myeloma, according to a review of 372 cases.

The findings, which showed a trend toward higher cumulative dosage and improved outcomes with the subcutaneous route, are consistent with those from a phase III study (Lancet Oncology. 2011;12[5]:431-40) of patients with relapsed or refractory multiple myeloma, Dr. Robert M. Rifkin reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.

Median treatment duration in 248 patients who received subcutaneous bortezomib and 124 who received intravenous bortezomib was similar at 4.4 and 4.1 months, respectively. Dose reductions were required in the first 16 weeks in 10% and 13% of patients in the groups, respectively, and median time to dose reduction was 49 days in both groups, said Dr. Rifkin of the Rocky Mountain Cancer Center, McKesson Specialty Health/US Oncology Network, Denver.

Median relative dose intensities were the same in the two groups, but the subcutaneous group had a higher median cumulative dose (25.8 mg/m² vs. 22.9 mg/m²). When dichotomized by median cumulative dose, those in the subcutaneous group were more likely to have received the higher dose (52% vs. 48%), he said, noting that a higher cumulative dose was associated with longer improved response and progression-free survival (PFS) at 12 weeks. The odds ratio for improved objective response with greater vs. less than 24.7 mg/m² was 2.20 and the hazard ratio for PFS was 0.34.

Two-year overall survival was similar at 81% and 78%; 2-year PFS was 75% and 70% in the groups, respectively.

Among 204 patients who were evaluable with respect to response, the complete response/very good partial response rates at a median of 19.1 and 20.8 months were16% and 22% in the subcutaneous and intravenous groups, respectively, Dr. Rifkin said.

Adverse events included neuropathy in 34% and 38%, thrombocytopenia in 13% and 10%, neutropenia in 10% and 5%, and anemia in 25% and 24% of patients in the groups, respectively.

The previously observed noninferiority of subcutaneous vs. intravenous bortezomib has the potential to affect treatment outcomes in the clinical setting, but there was a lack of comparative effectiveness data on the two treatment approaches as initial therapy in newly diagnosed multiple myeloma patients, he noted.

The current findings, based on adults treated between Jan. 1 and Dec. 31, 2012, within the McKesson Specialty Health/US Oncology Network, demonstrate a trend toward higher cumulative dose in the subcutaneous group, which was associated with improved response and PFS. The findings support extended therapy for higher cumulative dosage and better treatment outcomes, he concluded.

Dr. Rifkin is a board or advisory committee member for Celgene, Millenium: The Takeda Oncology Company, and Onyx.

[email protected]

CHICAGO – Subcutaneous and intravenous bortezomib performed comparably well in patients with newly diagnosed multiple myeloma, according to a review of 372 cases.

The findings, which showed a trend toward higher cumulative dosage and improved outcomes with the subcutaneous route, are consistent with those from a phase III study (Lancet Oncology. 2011;12[5]:431-40) of patients with relapsed or refractory multiple myeloma, Dr. Robert M. Rifkin reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.

Median treatment duration in 248 patients who received subcutaneous bortezomib and 124 who received intravenous bortezomib was similar at 4.4 and 4.1 months, respectively. Dose reductions were required in the first 16 weeks in 10% and 13% of patients in the groups, respectively, and median time to dose reduction was 49 days in both groups, said Dr. Rifkin of the Rocky Mountain Cancer Center, McKesson Specialty Health/US Oncology Network, Denver.

Median relative dose intensities were the same in the two groups, but the subcutaneous group had a higher median cumulative dose (25.8 mg/m² vs. 22.9 mg/m²). When dichotomized by median cumulative dose, those in the subcutaneous group were more likely to have received the higher dose (52% vs. 48%), he said, noting that a higher cumulative dose was associated with longer improved response and progression-free survival (PFS) at 12 weeks. The odds ratio for improved objective response with greater vs. less than 24.7 mg/m² was 2.20 and the hazard ratio for PFS was 0.34.

Two-year overall survival was similar at 81% and 78%; 2-year PFS was 75% and 70% in the groups, respectively.

Among 204 patients who were evaluable with respect to response, the complete response/very good partial response rates at a median of 19.1 and 20.8 months were16% and 22% in the subcutaneous and intravenous groups, respectively, Dr. Rifkin said.

Adverse events included neuropathy in 34% and 38%, thrombocytopenia in 13% and 10%, neutropenia in 10% and 5%, and anemia in 25% and 24% of patients in the groups, respectively.

The previously observed noninferiority of subcutaneous vs. intravenous bortezomib has the potential to affect treatment outcomes in the clinical setting, but there was a lack of comparative effectiveness data on the two treatment approaches as initial therapy in newly diagnosed multiple myeloma patients, he noted.

The current findings, based on adults treated between Jan. 1 and Dec. 31, 2012, within the McKesson Specialty Health/US Oncology Network, demonstrate a trend toward higher cumulative dose in the subcutaneous group, which was associated with improved response and PFS. The findings support extended therapy for higher cumulative dosage and better treatment outcomes, he concluded.

Dr. Rifkin is a board or advisory committee member for Celgene, Millenium: The Takeda Oncology Company, and Onyx.

[email protected]

CHICAGO – Subcutaneous and intravenous bortezomib performed comparably well in patients with newly diagnosed multiple myeloma, according to a review of 372 cases.

The findings, which showed a trend toward higher cumulative dosage and improved outcomes with the subcutaneous route, are consistent with those from a phase III study (Lancet Oncology. 2011;12[5]:431-40) of patients with relapsed or refractory multiple myeloma, Dr. Robert M. Rifkin reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.

Median treatment duration in 248 patients who received subcutaneous bortezomib and 124 who received intravenous bortezomib was similar at 4.4 and 4.1 months, respectively. Dose reductions were required in the first 16 weeks in 10% and 13% of patients in the groups, respectively, and median time to dose reduction was 49 days in both groups, said Dr. Rifkin of the Rocky Mountain Cancer Center, McKesson Specialty Health/US Oncology Network, Denver.

Median relative dose intensities were the same in the two groups, but the subcutaneous group had a higher median cumulative dose (25.8 mg/m² vs. 22.9 mg/m²). When dichotomized by median cumulative dose, those in the subcutaneous group were more likely to have received the higher dose (52% vs. 48%), he said, noting that a higher cumulative dose was associated with longer improved response and progression-free survival (PFS) at 12 weeks. The odds ratio for improved objective response with greater vs. less than 24.7 mg/m² was 2.20 and the hazard ratio for PFS was 0.34.

Two-year overall survival was similar at 81% and 78%; 2-year PFS was 75% and 70% in the groups, respectively.

Among 204 patients who were evaluable with respect to response, the complete response/very good partial response rates at a median of 19.1 and 20.8 months were16% and 22% in the subcutaneous and intravenous groups, respectively, Dr. Rifkin said.

Adverse events included neuropathy in 34% and 38%, thrombocytopenia in 13% and 10%, neutropenia in 10% and 5%, and anemia in 25% and 24% of patients in the groups, respectively.

The previously observed noninferiority of subcutaneous vs. intravenous bortezomib has the potential to affect treatment outcomes in the clinical setting, but there was a lack of comparative effectiveness data on the two treatment approaches as initial therapy in newly diagnosed multiple myeloma patients, he noted.

The current findings, based on adults treated between Jan. 1 and Dec. 31, 2012, within the McKesson Specialty Health/US Oncology Network, demonstrate a trend toward higher cumulative dose in the subcutaneous group, which was associated with improved response and PFS. The findings support extended therapy for higher cumulative dosage and better treatment outcomes, he concluded.

Dr. Rifkin is a board or advisory committee member for Celgene, Millenium: The Takeda Oncology Company, and Onyx.

[email protected]

CHICAGO – Statin use is associated with a decrease in the prevalence of skeletal-related events in patients with stage I multiple myeloma, findings from a review of 120 cases suggest.

The prevalence of skeletal-related events (SREs) was 35% in 54 patients who had been treated with statins, compared with 56% in 66 statin-naive patients. The difference between the groups remained significant after adjusting for bisphosphonate use, calcium and vitamin D supplementation, history of osteoporosis, and second malignancy, Dr. Fernando Vargas of the University of Miami reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.

Study subjects were adults with multiple myeloma seen at a single institution between 2007 and 2012. Those with statin use prior to the development of SREs – defined as pathologic fractures, necessity of orthopedic intervention, radiation therapy, or spinal cord compression – were included. Patients with smoldering myeloma or monoclonal gammopathy of indeterminate significance were excluded.

The statin-experienced and statin-naive groups were similar with respect to smoking history, alcohol abuse, documented diagnosis of osteoporosis, coexistent malignancy, hypothyroidsim, Paget’s disease of the bone, and use of bisphosphonates or calcium plus vitamin D supplementation. The groups also were similar with respect to distribution of cancer staging, and after correcting for International Surgical Staging stage, the SRE risk reduction associated with statin use was significant only in patients with stage I multiple myeloma. One patient with stage I disease (10%) in the statin-experienced group developed SREs, compared with 6 (62%) in the statin-naive group, Dr. Vargas said.

SREs are associated with significant morbidity and mortality in patients with multiple myeloma, and the results of studies assessing the effect of statins on overall disease response in myeloma patients undergoing chemotherapy have been conflicting, he explained, noting that “this analysis was proposed on the grounds that statins inhibit the mevalonic acid pathway upstream from the site of action of bisphosphonates (i.e. famesyl diphosphate synthase blockade), an integral part of multiple myeloma supportive treatment.”

He and his colleagues hypothesized that, given their site of action, statins would have bone protective effects.

Indeed, statins were found to be associated with a decrease in the prevalence of SREs in patients with stage I multiple myeloma, he said.

“Given the well documented safety profile of statins and their ease of use, we suggest that a prospective study be done to further assess their role in the prevention of SREs in multiple myeloma patients,” he concluded, noting that the findings in ISS stage I patients also suggest a possible role for statin use in patients with high-risk smoldering myeloma.

Dr. Vargas reported having no disclosures.

[email protected]

CHICAGO – Statin use is associated with a decrease in the prevalence of skeletal-related events in patients with stage I multiple myeloma, findings from a review of 120 cases suggest.

The prevalence of skeletal-related events (SREs) was 35% in 54 patients who had been treated with statins, compared with 56% in 66 statin-naive patients. The difference between the groups remained significant after adjusting for bisphosphonate use, calcium and vitamin D supplementation, history of osteoporosis, and second malignancy, Dr. Fernando Vargas of the University of Miami reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.

Study subjects were adults with multiple myeloma seen at a single institution between 2007 and 2012. Those with statin use prior to the development of SREs – defined as pathologic fractures, necessity of orthopedic intervention, radiation therapy, or spinal cord compression – were included. Patients with smoldering myeloma or monoclonal gammopathy of indeterminate significance were excluded.

The statin-experienced and statin-naive groups were similar with respect to smoking history, alcohol abuse, documented diagnosis of osteoporosis, coexistent malignancy, hypothyroidsim, Paget’s disease of the bone, and use of bisphosphonates or calcium plus vitamin D supplementation. The groups also were similar with respect to distribution of cancer staging, and after correcting for International Surgical Staging stage, the SRE risk reduction associated with statin use was significant only in patients with stage I multiple myeloma. One patient with stage I disease (10%) in the statin-experienced group developed SREs, compared with 6 (62%) in the statin-naive group, Dr. Vargas said.

SREs are associated with significant morbidity and mortality in patients with multiple myeloma, and the results of studies assessing the effect of statins on overall disease response in myeloma patients undergoing chemotherapy have been conflicting, he explained, noting that “this analysis was proposed on the grounds that statins inhibit the mevalonic acid pathway upstream from the site of action of bisphosphonates (i.e. famesyl diphosphate synthase blockade), an integral part of multiple myeloma supportive treatment.”

He and his colleagues hypothesized that, given their site of action, statins would have bone protective effects.

Indeed, statins were found to be associated with a decrease in the prevalence of SREs in patients with stage I multiple myeloma, he said.

“Given the well documented safety profile of statins and their ease of use, we suggest that a prospective study be done to further assess their role in the prevention of SREs in multiple myeloma patients,” he concluded, noting that the findings in ISS stage I patients also suggest a possible role for statin use in patients with high-risk smoldering myeloma.

Dr. Vargas reported having no disclosures.

[email protected]

CHICAGO – Statin use is associated with a decrease in the prevalence of skeletal-related events in patients with stage I multiple myeloma, findings from a review of 120 cases suggest.

The prevalence of skeletal-related events (SREs) was 35% in 54 patients who had been treated with statins, compared with 56% in 66 statin-naive patients. The difference between the groups remained significant after adjusting for bisphosphonate use, calcium and vitamin D supplementation, history of osteoporosis, and second malignancy, Dr. Fernando Vargas of the University of Miami reported in a poster at the American Society of Hematology Meeting on Hematologic Malignancies.

Study subjects were adults with multiple myeloma seen at a single institution between 2007 and 2012. Those with statin use prior to the development of SREs – defined as pathologic fractures, necessity of orthopedic intervention, radiation therapy, or spinal cord compression – were included. Patients with smoldering myeloma or monoclonal gammopathy of indeterminate significance were excluded.

The statin-experienced and statin-naive groups were similar with respect to smoking history, alcohol abuse, documented diagnosis of osteoporosis, coexistent malignancy, hypothyroidsim, Paget’s disease of the bone, and use of bisphosphonates or calcium plus vitamin D supplementation. The groups also were similar with respect to distribution of cancer staging, and after correcting for International Surgical Staging stage, the SRE risk reduction associated with statin use was significant only in patients with stage I multiple myeloma. One patient with stage I disease (10%) in the statin-experienced group developed SREs, compared with 6 (62%) in the statin-naive group, Dr. Vargas said.

SREs are associated with significant morbidity and mortality in patients with multiple myeloma, and the results of studies assessing the effect of statins on overall disease response in myeloma patients undergoing chemotherapy have been conflicting, he explained, noting that “this analysis was proposed on the grounds that statins inhibit the mevalonic acid pathway upstream from the site of action of bisphosphonates (i.e. famesyl diphosphate synthase blockade), an integral part of multiple myeloma supportive treatment.”

He and his colleagues hypothesized that, given their site of action, statins would have bone protective effects.

Indeed, statins were found to be associated with a decrease in the prevalence of SREs in patients with stage I multiple myeloma, he said.

“Given the well documented safety profile of statins and their ease of use, we suggest that a prospective study be done to further assess their role in the prevention of SREs in multiple myeloma patients,” he concluded, noting that the findings in ISS stage I patients also suggest a possible role for statin use in patients with high-risk smoldering myeloma.

Dr. Vargas reported having no disclosures.

[email protected]