When is denosumab an option in myeloma?

 

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

Those guidelines recommend pamidronate or zoledronic acid for patients with active symptomatic myeloma who need systemic therapy. They describe denosumab as an “alternative” based on recent noninferiority data; however, they add that denosumab is associated with less renal toxicity compared with zoledronic acid or pamidronate, and thus, “may be preferred” in that setting.

The second scenario for denosumab use is in patients who aren’t tolerating bisphosphonates: “We switch them from zoledronic acid to pamidronate, and they still have terrible acute phase reactions,” Dr. Roodman said.

Dr. Roodman’s comments on use of denosumab were in response to an audience question about when he would use denosumab, given the considerable cost difference between the RANK ligand inhibitor and bisphosphonates.

The recent ASCO guidelines, of which Dr. Roodman is a coauthor, state that denosumab “is more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions.”

Previously, ASCO guidelines recommended use of intravenous bisphosphonates for patients with myeloma and evidence of bone disease. Based on consideration of new evidence, the guideline authors eliminated the requirement for evidence of bone disease and added denosumab as an alternative treatment choice.

 

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

 

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

 

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

Those guidelines recommend pamidronate or zoledronic acid for patients with active symptomatic myeloma who need systemic therapy. They describe denosumab as an “alternative” based on recent noninferiority data; however, they add that denosumab is associated with less renal toxicity compared with zoledronic acid or pamidronate, and thus, “may be preferred” in that setting.

The second scenario for denosumab use is in patients who aren’t tolerating bisphosphonates: “We switch them from zoledronic acid to pamidronate, and they still have terrible acute phase reactions,” Dr. Roodman said.

Dr. Roodman’s comments on use of denosumab were in response to an audience question about when he would use denosumab, given the considerable cost difference between the RANK ligand inhibitor and bisphosphonates.

The recent ASCO guidelines, of which Dr. Roodman is a coauthor, state that denosumab “is more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions.”

Previously, ASCO guidelines recommended use of intravenous bisphosphonates for patients with myeloma and evidence of bone disease. Based on consideration of new evidence, the guideline authors eliminated the requirement for evidence of bone disease and added denosumab as an alternative treatment choice.

 

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

 

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

 

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

Those guidelines recommend pamidronate or zoledronic acid for patients with active symptomatic myeloma who need systemic therapy. They describe denosumab as an “alternative” based on recent noninferiority data; however, they add that denosumab is associated with less renal toxicity compared with zoledronic acid or pamidronate, and thus, “may be preferred” in that setting.

The second scenario for denosumab use is in patients who aren’t tolerating bisphosphonates: “We switch them from zoledronic acid to pamidronate, and they still have terrible acute phase reactions,” Dr. Roodman said.

Dr. Roodman’s comments on use of denosumab were in response to an audience question about when he would use denosumab, given the considerable cost difference between the RANK ligand inhibitor and bisphosphonates.

The recent ASCO guidelines, of which Dr. Roodman is a coauthor, state that denosumab “is more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions.”

Previously, ASCO guidelines recommended use of intravenous bisphosphonates for patients with myeloma and evidence of bone disease. Based on consideration of new evidence, the guideline authors eliminated the requirement for evidence of bone disease and added denosumab as an alternative treatment choice.

 

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

 

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.