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Progress in the Treatment of Multiple Myeloma

Insights From: Kenneth C. Anderson, MD, Dana-Farber Cancer Institute and Harvard Medical School; Rafael Fonseca, MD, Mayo Clinic; Noopur S. Raje, MD, Massachusetts General Hospital Cancer Center
Published: Thursday, Jan 17, 2019



Transcript: 

Kenneth C. Anderson, MD: In myeloma there has literally been a revolution in new therapies over the last 15 to 20 years. Before that time, we treated myeloma with conventional chemotherapy, either low-dose or high-dose in stem cell transplantation. But now in the last 15 to 20 years we have the development of the immunomodulatory drugs lenalidomide and pomalidomide; the proteasome inhibitors bortezomib, carfilzomib, and ixazomib; an HDAC [histone deacetylase] inhibitor panobinostat; and the monoclonal antibodies daratumumab and elotuzumab. And those agents either used alone or in combinations now at all the different stages of disease, from newly diagnosed to relapse to relapse/refractory to maintenance, have literally transformed patient outcome. The progression-free survival is now 3 to 4 times longer than it was.

Even more excitingly there’s great hope for the future in novel agents. So many people now with myeloma actually can grow old and live a normal lifespan and celebrate the milestones of life with their families.

Smoldering multiple myeloma patients right now do not receive systemic therapy outside of a clinical protocol. It turns out in myeloma since we have these effective agents—the immunomodulatory drugs, proteasome inhibitors, and HDAC inhibitor and monoclonal antibodies—they’re effective and don’t have a lot of adverse effects. We have changed the definitions of who has active myeloma. To be more clear, patients in the past were only treated when they developed complications of the disease—high blood calcium, kidney problems, anemia, or bone disease. But nowadays even in the absence of those clinical sequelae, we treat patients who have more than 60% bone marrow plasma cells, a higher kappa/lambda ratio 100-fold or greater, or who have bone lesions on sensitive imaging.

Those patients are now treated. So the patients who have smoldering multiple myeloma traditionally are not treated. However, in that group of smoldering myeloma, if they have more than 20% plasma cells, if they have a kappa/lambda ratio of 20-fold abnormal or greater and still don’t have the calcium, kidney, anemia and bone disease, they are at high risk to transform or to progress to myeloma. So those patients are treated on protocol.

For example, there is one particular protocol I’ll mention to you, from our institution, the elotuzumab monoclonal antibody combined with lenalidomide and dexamethasone given to 50 patients who have this risk of progressing to active disease. And when that was given we have high response rates, as you would expect, monoclonal proteins decreasing 84% of the time. And we have very few if any progression to active myeloma at this time, although it’s still very early. But the concept is here. We can now take active medicines, move them earlier, and we may be able to delay, and maybe someday prevent, the development of active disease.

Transcript Edited for Clarity 
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Transcript: 

Kenneth C. Anderson, MD: In myeloma there has literally been a revolution in new therapies over the last 15 to 20 years. Before that time, we treated myeloma with conventional chemotherapy, either low-dose or high-dose in stem cell transplantation. But now in the last 15 to 20 years we have the development of the immunomodulatory drugs lenalidomide and pomalidomide; the proteasome inhibitors bortezomib, carfilzomib, and ixazomib; an HDAC [histone deacetylase] inhibitor panobinostat; and the monoclonal antibodies daratumumab and elotuzumab. And those agents either used alone or in combinations now at all the different stages of disease, from newly diagnosed to relapse to relapse/refractory to maintenance, have literally transformed patient outcome. The progression-free survival is now 3 to 4 times longer than it was.

Even more excitingly there’s great hope for the future in novel agents. So many people now with myeloma actually can grow old and live a normal lifespan and celebrate the milestones of life with their families.

Smoldering multiple myeloma patients right now do not receive systemic therapy outside of a clinical protocol. It turns out in myeloma since we have these effective agents—the immunomodulatory drugs, proteasome inhibitors, and HDAC inhibitor and monoclonal antibodies—they’re effective and don’t have a lot of adverse effects. We have changed the definitions of who has active myeloma. To be more clear, patients in the past were only treated when they developed complications of the disease—high blood calcium, kidney problems, anemia, or bone disease. But nowadays even in the absence of those clinical sequelae, we treat patients who have more than 60% bone marrow plasma cells, a higher kappa/lambda ratio 100-fold or greater, or who have bone lesions on sensitive imaging.

Those patients are now treated. So the patients who have smoldering multiple myeloma traditionally are not treated. However, in that group of smoldering myeloma, if they have more than 20% plasma cells, if they have a kappa/lambda ratio of 20-fold abnormal or greater and still don’t have the calcium, kidney, anemia and bone disease, they are at high risk to transform or to progress to myeloma. So those patients are treated on protocol.

For example, there is one particular protocol I’ll mention to you, from our institution, the elotuzumab monoclonal antibody combined with lenalidomide and dexamethasone given to 50 patients who have this risk of progressing to active disease. And when that was given we have high response rates, as you would expect, monoclonal proteins decreasing 84% of the time. And we have very few if any progression to active myeloma at this time, although it’s still very early. But the concept is here. We can now take active medicines, move them earlier, and we may be able to delay, and maybe someday prevent, the development of active disease.

Transcript Edited for Clarity 
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