Multiple myeloma (MM) is considered an incurable disease with inevitable relapse and ongoing unmet needs, leaving no clear way forward. Patients face a difficult journey ahead, as every relapse they experience typically brings1-4:
Watch Dr. Joshua Richter discuss current challenges in the management of MM
Hello, I’m Dr Joshua Richter. I’m an associate professor of medicine at The Tisch Cancer Institute, Icahn School of Medicine, and the director of multiple myeloma at The Blavatnik Family Chelsea Medical Center at Mount Sinai. I will be discussing the current challenges for patients with multiple myeloma and sharing thoughts on treatment approaches for patients with relapsed/refractory disease.
What are some unmet needs for patients with relapsed/refractory multiple myeloma?
Multiple myeloma is considered an incurable disease, and relapse is unfortunately inevitable. With each relapse, the disease can become more resistant, and in turn subsequent treatments can have less deep—and therefore less durable—remissions. Throughout the disease course, most patients receive multiple lines of therapy, with not only the potential for progressive decline in clinical outcomes, but also worsening toxicities and diminishing quality of life. Toxicities can take many forms, from traditional disease and treatment-related adverse events to more global challenges such as financial, emotional, and spiritual burdens. The uncertainty, fear of relapse, and subsequent decrease in treatment options can take a considerable emotional toll. Therefore, there is a need for therapies that prolong treatment remission and maintain quality of life. New treatments, such as BCMA-directed therapies, are emerging in the clinic and have the potential of meaningful clinical responses in relapsed/refractory multiple myeloma.
How do you select a treatment approach for patients with relapsed/refractory multiple myeloma?
In multiple myeloma, the disease is complex, and the patients are diverse. As there are oftentimes multiple potential options for patients, I turn to 3 key factors that guide our treatment decisions: patient-related factors, disease-related factors, and treatment-related factors.
For patient-related factors, I typically take into account whether the patient is fit or frail, has significant comorbidities, or patient preferences. I consider whether the disease is undergoing a biochemical relapse or a clinical one, with new CRAB symptoms, whether the disease is growing fast and if there is extramedullary disease. And for treatment-related factors, I assess what therapies the patient has had before, how they responded, what they are refractory to, and what they have residual toxicities to.
Taking all this into consideration, these 3 key factors shape the current approach in selecting treatment for patients with relapsed/refractory multiple myeloma.
I hope this helps you further understand the challenges and ongoing needs of patients with multiple myeloma. I am excited for the new and emerging approaches in this field, such as BCMA-directed therapies. Thank you for joining us today and for caring for patients with multiple myeloma.
The immune system has the natural ability to recognize and eliminate tumor cells – it exerts selective pressure on susceptible tumor clones. However, in MM, if the immune response fails to completely eliminate the tumor, tumor cell variants develop which are able to resist, avoid, or suppress the antitumor immune response.6
MM cells, together with their bone marrow microenvironment, express co-inhibitory molecules and immunosuppressive cytokines, leading to immune dysfunction7,8
Watch this video to discover the role of immune dysfunction in MM
Narrator: Immunosuppression in Multiple Myeloma (MM)
For patients with multiple myeloma, each relapse after a treatment response has a higher risk of treatment resistance, shorter remission, and lesser response to standard treatments than earlier courses of therapy. New treatments are needed for relapsed and refractory multiple myeloma that counter the mechanisms for treatment resistance, including immune evasion. Bidirectional interplay of immunosuppressive factors between multiple myeloma cells and accessory cells in the tumor microenvironment suppress the immune bone marrow milieu leading to immune exhaustion. Ongoing research is investigating the benefit of therapies targeting multiple myeloma cell-surface antigens on multiple myeloma cells.
The cell-surface proteins CD38, CD138, GPRC5D, SLAMF7, TACI, and BCMA are targets for agents approved or currently under investigation for multiple myeloma.
Innovative approaches that enhance tumor-specific immune activity with the potential to provide deep and durable responses and improve QOL are urgently needed for all patients, including those with varying clinical risk factors, performance status, and prior therapies.1,4,5
Ongoing research is investigating the potential therapeutic benefit of B-cell maturation antigen (BCMA)-directed treatment approaches to elicit an antitumor immune response1,9
CD=cluster of differentiation; CRAB=hypercalcemia, renal insufficiency, anemia, bone lesions; GPRC5D=G-protein coupled receptor family C group 5 member D; SLAMF7=signaling lymphocytic activation molecule family member 7; TACI=transmembrane activator and calcium modulation ligand interactor.