ADC, bsAb, and CAR-T Therapy Compete for Multiple Myeloma Market Touching USD 12 Billion

Multiple Myeloma (MM) is a malignant tumor, which is caused by malignant proliferation of plasma cells, extensive infiltration and secretion of monoclonal immunoglobulin. As the second most common malignant tumor of the hematological system, MM accounts for about 10% of hematological malignancies. It occurs mostly in old age and its common clinical symptoms are myeloma-related organ damage, that is, CRAB symptoms, including Calcium elevation, Renal insufficiency, Anemia, Bone disease, and secondary Amyloidosis and so on.

MM is still incurable to some extent since recurrence and treatment refractory are still the main problems. This has prompted people to constantly search for new molecular targets and carefully design drugs that regulate the effects of these targets. In the past decade, the focus has shifted from systemic treatments (such as chemotherapy) to targeted treatments (such as immunotherapy). CAR-T cell therapy, antibody-drug conjugate, bispecific antibodies and other innovative targeted therapies are progressing rapidly for MM treatment.

Monoclonal Antibody

A monoclonal antibody is produced by cloning a single B cell and targets only one specific antigen. It is usually prepared by hybridoma technology, which combines sensitized B cells with the ability to secrete specific antibodies and myeloma cells with immortal proliferation into B cell hybridoma based on cell fusion technology.

The first immunotherapies approved for MM treatment were monoclonal antibodies, Daratumumab and Elotuzumab. The third monoclonal antibody, Isatuximab, was approved for relapsed refractory MM in March 2020.

CAR-T Cell Therapy

Another type of immunotherapy for MM is to target another target on the surface of myeloma cells—B cell maturation antigen (BCMA), which is not found on healthy cells. The most promising of BCMA targeted therapy is chimeric antigen receptor T cell (CAR-T cell) therapy.

Many pharmaceutical companies are in clinical trials for anti-BCMA CAR-T therapy for MM, and there is no corresponding CAR-T product on the market. Although the results of clinical trials are encouraging, CAR-T therapy can not completely eliminate MM, and the high cost will be the main factor determining the availability of CAR-T therapy. It is estimated that the cost of each dose is about hundreds of thousands of dollars, and as MM may relapse, one dose may not be enough.

Antibody-drug Conjugate

Although CAR-T therapy has received the greatest attention from the media, it is not the only promising immunotherapy. Researchers are also interested in antibody-drug conjugates (ADCs). For example, the United States Food and Drug Administration (FDA) has accelerated the approval of GlaxoSmithKline (GSK)'s Blenrep (belantamab mafodotin) as a monotherapy for adult patients with relapsed or refractory MM, which is the first approved anti-BCMA ADC.

Compared with CAR-T therapy, ADCs are inexpensive, easy to manufacture and manage. They also do not cause cytokine release syndrome. However, they may still cause adverse reactions, such as corneal disease, nausea, fever, and fatigue.

Bispecific Antibody

Another antibody-based treatment for MM is a bispecific antibody (bsAb) that binds to the BCMA antigen and CD3 protein on the surface of T cells. This combination activates T cells and brings them close to the tumor, thereby killing the tumor. But so far, the response rate to patients with MM of it has been lower than CAR-T therapy.

A key benefit of bsAbs is that no conditional chemotherapy is required before treatment. In contrast, people receiving CAR-T cells must first receive a chemotherapy that reduces lymphocytes to give CAR-T cells the best chance to fight cancer. However, bsAbs do have some of the same side effects as CAR-T cell therapy, including cytokine release syndrome and neurotoxicity.

According to Datamonitor Healthcare’s forecast, the scale of mainstream MM drugs in major countries (the United States, Japan, France, Germany, Italy, Spain, and the United Kingdom) totals approximately $12 billion, and will maintain a growth of 5-8% in the next 3-5 years. Different innovative drugs will enter this blue ocean, and with the right combination of drugs, we can finally find effective treatments for most patients with MM.