Research Highlight: Changing the Landscape of Treatment for Multiple Myeloma (Part 1)

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Multiple myeloma (MM) made up close to 20% of all new blood cancer cases diagnosed in the US in 2019. This disease is characterized by the uncontrolled proliferation of abnormal monoclonal plasma cells in the bone marrow. As these abnormal cells grow in excess, they disrupt normal cell production, which can result in a range of complications, particularly in the bones, blood, kidney and immune system. People with multiple myeloma develop tumors in more than one location inside and sometimes outside of the bone marrow, hence the name ‘multiple’ myeloma.

Among the risk factors for MM is advanced age, as it is primarily a disease of older people (65 and above) and the risk of developing myeloma further increases with age. Men are also more likely to develop MM versus women. In addition family history, radiation exposure, workplace exposure, racial, and ancestral background also play a major role in MGUS, SMM and MM incidence. Both MGUS and MM are two to threefold more common in African Americans, Afro-Caribbeans, and Africans compared with persons of European ancestry. MM is the most common hematological malignancy in African Americans. For more information please visit the LLS Myeloma Link Program created to enhance Myeloma knowledge and access to latest treatments in African Americans Communities to increase access to education and treatment for myeloma in the African Americans communities.

Virtually all MM cases begin as the pre-malignant plasma cell disorders monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) and usually neither of them presents with symptoms. MGUS is present in around 3% of the general white population of age 50 and older, with people of African ancestry showing 2- to 3-fold higher prevalence. Why some people with MGUS develop MM and others do not is currently unknown. Smoldering multiple myeloma (SMM) is a slow-growing type of MM, considered an intermediate stage between MGUS and MM. For both MM precursor diseases, current clinical practice relies on careful lifelong surveillance, although experimental clinical trials are evaluating therapies for high risk patients that are typically used to treat MM. LLS supports a wide variety of grants aimed specifically of investigating these precursor states of myeloma in order to learn how MM develops and progresses.

Recently Approved Treatments of MM

Patients with active MM require therapy; such as chemotherapy, proteasome inhibitors (Bortezomib, Carfilzomib and Ixazomib), immunomodulatory IMiDs (Thalidomide, Lenalidomide and Pomalidomide), Histone deacetylase (HDAC) inhibitors (Panobinostat) and monoclonal antibodies (Daratumumab, Elotuzumab and Isatuximab). Chemotherapy plus stem cell transplant has also been the standard treatment. LLS advanced many of these to approval and current clinical use.

One of the more recent approvals for MM came July 2019, when Xpovio (Selinexor) was approved for relapsed or refractory multiple myeloma (R/R MM). This drug has received extensive support from LLS: over $4M in 9 grants for acute myeloid leukemia, chronic lymphocytic leukemia, diffuse large B-cell lymphoma and for multiple myeloma. Earlier this year in March, the FDA approved Sarclisa (isatuximab-irfc), in combination with pomalidomide and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma. Currently, one project in the SCOR grant of Robert Z. Orlowski, M.D., Ph.D. (MD Anderson) is a multi-center clinical trial of isatuximab in high-risk smoldering myeloma (SMM) exploring the use of this monoclonal anti-CD38 antibody in the precursor disease of MM. More about Dr. Orlowski’s published research at https://faculty.mdanderson.org/profiles/robert_orlowski.html.

The most recent approval of daratumumab and hyaluronidase-fihj for adult patients with newly diagnosed or relapsed/refractory multiple myeloma occurred in May 2020. Daratumumab and hyaluronidase-fihj is approved for the following indications that intravenous daratumumab had previously received: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant, in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy, in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy, as monotherapy, and in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.

For more information on treatment options, myeloma and LLS resources, please contact an Information Specialist.

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