Multiple Myeloma: Considering First-Line Treatment Options

September is Blood Cancer, Leukemia, and Lymphoma Awareness Month, and the Association of Community Cancer Centers (ACCC) is collaborating with the Leukemia & Lymphoma Society to offer programs focused on improving care for patients with hematologic malignancies, including multiple myeloma.

Multiple myeloma is a rare cancer of plasma cells. Abnormal plasma cells accumulate in the bone marrow, crowding out healthy cells and causing low blood counts, bone lesions, high calcium levels, infections, and kidney damage or failure. Although rare (accounting for 1% of cancer cases overall), it is the third most prevalent blood cancer after non-Hodgkin’s lymphoma and leukemia.

Currently, there is no cure for multiple myeloma, but there are treatment options that can help people with the disease live longer, healthier lives. Stem cell transplant is a standard of care for eligible patients. However, over half of those who are newly diagnosed with multiple myeloma are not eligible for transplant due to age or other major health problems, such as heart, lung, liver, or kidney disease. 

To raise awareness among cancer programs and practices about treatment options for newly diagnosed patients with multiple myeloma who are ineligible for transplant, ACCC developed an educational initiative: Changing Treatment Paradigms for Patients with Multiple Myeloma.

Key topics this initiative intends to cover include: 

• Advent of subcutaneous forms of medication 
• Combination medications (all oral-based combinations) 
• Triplet vs. quadruplet regimens for first-line treatment  
• Treatment sequencing for multiple myeloma.

ACCCBuzz spoke with Dan Vogl, MD, MSCE, director of the Abramson Cancer Center Clinical Research Unit at Penn Presbyterian Medical Center – Abramson Cancer Center, and associate professor of Medicine at the University of Pennsylvania. He specializes in hematologic cancers, including multiple myeloma.

ACCCBuzz: What is the primary treatment for multiple myeloma?

Dr. Vogl: The primary approach of modern myeloma therapy is to combine chemotherapy agents to create regimens that produce deep and durable responses with low levels of toxicity. Typical treatment regimens consist of three or four agents, each from a different class of medication. 

ACCCBuzz: What are anti-CD38 (cluster of differentiation 38) antibodies, and what do they do for patients? 

Dr. Vogl: Monoclonal antibodies are one class of anti-cancer agents. They are immune proteins produced in a laboratory that bind to a specific target, usually on the surface of cancer cells, to induce an immune response that then kills the cancer cells. The main important target of monoclonal antibodies on the surface of multiple myeloma cells is a protein called CD38, and there are two anti-CD38 antibody medications currently approved by the FDA [U.S. Food and Drug Administration] for the treatment of multiple myeloma: isatuximab and daratumumab, incusing the daratumumab and hyaluronidase-fihj combination.

Overall, these anti-CD38 antibody medications are very well tolerated and can be very effective. The main side effects are infusion reactions (often with the first dose) and immune suppression (which also occurs from multiple myeloma itself). 

ACCCBuzz: Why would these be used over some of the other treatment options?

Dr. Vogl: With many medications available to treat multiple myeloma, I think that the most important question is not which medication should be used, but which combinations of drugs work best. The current standard of care is to include an anti-CD38 monoclonal antibody in either first- or second-line treatment of multiple myeloma. The combination of effectiveness and low side effects makes these agents particularly good choices for almost all patients. These anti-CD38 monoclonal antibodies are typically combined with immunomodulatory drugs, such as lenalidomide or pomalidomide; with proteasome inhibitors like bortezomib or carfilzomib; as well as with steroid medications, such as dexamethasone.

ACCCBuzz: There are some that note this treatment helps reduce the time patients spend in the chair (getting treated). Can you explain how this helps?

Dr. Vogl: When anti-CD38 antibodies first became part of multiple myeloma therapy in 2015, the only option was intravenous daratumumab. It had a pretty high rate of infusion reactions, causing reactions in about half of patients during the first dose. These infusion reactions are different in each patient but usually include symptoms like fever, chills, shortness of breath, wheezing, itching, hives, and/or low blood pressure. Severe reactions are very rare, and the reactions are usually managed by stopping the infusion, waiting for the reaction to subside, and then restarting it at a slower rate. Because of this, intravenous daratumumab needed to be given very slowly, over about eight hours. The risk of infusion reactions got much lower with later doses, which could be given as quickly as 3.5 hours. 

Isatuximab, which is also provided as an intravenous option, can be given faster than intravenous daratumumab, with about the same frequency of infusion reactions. Isatuximab takes about 3.5 hours for the first dose and as fast as 1.25 hours for later doses, which definitely represents an improvement in convenience.

Daratumumab is now available in a subcutaneous formulation (injected under the skin) as daratumumab and hyaluronidase-fihj. This subcutaneous daratumumab is even faster, taking only about five minutes to administer and has less frequent reactions, affecting just over 10 percent of patients. So the subcutaneous formulation of daratumumab has been a major advance in convenience for both patients and infusion units.

ACCCBuzz: What are the overall benefits and risks to patients?

Dr. Vogl: Anti-CD38 antibodies have been shown to lead to multiple myeloma responses, even when just given on their own, and they have been shown to improve the depth and duration of responses when given in combination with other anti-multiple myeloma agents. Patients should expect that they could have an infusion reaction with the first dose, but later doses usually do not cause any side effects. Immune suppression is a concern with these medications, and we typically recommend that patients take an anti-viral antibiotic to prevent reactivation of the chicken pox virus as shingles while they are receiving an anti-CD38 antibody. 

Overall, isatuximab and daratumumab, including daratumumab and hyaluronidase-fihj, are great treatment options for multiple myeloma, and they are typically used in combination with other anti-myeloma agents.

Learn More

For more information on this multiple myeloma program, contact Regina Gibson-Burtnick, ACCC assistant program manager, or visit ACCC’s website.

To access multiple myeloma education and support resources for your patients, including booklets, videos, financial support, and peer to peer support, encourage them to visit the Leukemia & Lymphoma Society's website. Healthcare professionals can also access podcasts about treating multiple myeloma by visiting the society's podcast page.

The Changing Treatment Paradigms for Patients with Multiple Myeloma education initiative is made possible by support from Johnson & Johnson.