Multiple myeloma (MM) is a currently incurable blood cancer that begins in plasma cells, a type of white blood cell, that produce antibodies to fight bacteria and viruses entering the body.
When plasma cells become cancerous myeloma cells, they are unable to perform their usual function, and their increased numbers make less room for healthy red blood cells, white blood cells and platelets—a condition that may cause anemia and increases the patient’s risk of infection. The myeloma cells often form tumors primarily, appearing similar to holes in the bone, aka lytic lesions.
The OSUCCC – James has a team of physicians who specialize in diagnosing and treating MM. With diagnostic, research and treatment areas under one roof, these experts can quickly translate scientific advances to innovative patient care that extends lives and offers hope for patients and families.
The Multiple Myeloma Program’s research focuses on:
- Evaluating new targeted therapies for multiple myeloma that have shown some benefit in other studies
- Designing innovative clinical trials that efficiently combine novel and standard anticancer agents for multiple myeloma and its complications
- Applying discoveries in the laboratory to develop novel therapies for multiple myeloma
Here are examples of recent grants awarded to OSUCCC – James researchers for multiple myeloma treatment:
Personalizing Multiple Myeloma Treatment
Funded by a $100,000, two-year Idea Grant from revenue generated by Pelotonia, an annual grassroots bicycle tour that raises money for cancer research at the OSUCCC – James.
PIs: Mitch Phelps, PhD; Ming Poi, Pharm D, PhD; Craig Hofmeister, MD, MPH
- Develop a personalized calculator to help clinicians individualize dosing of a drug called melphalan to maximize the killing of myeloma cells while minimizing the drug’s harsh side effects in patients with myeloma
A Phase I/II trial of CT-011 and lenalidomide for multiple myeloma
Funded by a four-year $720,000 grant from the American Cancer Society.
PI: Don Benson, MD, PhD
- Conduct a Phase I/II study of CT-011 and len in patients with relapsed/refractory multiple myeloma
- Assess the correlative effects of combination therapy with CT-011 and len on T cells and NK cells in patients with relapsed/refractory multiple myeloma
NCCN Senior Adult Oncology: Myeloma Comprehensive Geriatric Assessment and Biomarkers of Aging Investigation
Funded by a two-year $150,000 grant from the National Comprehensive Cancer Network to improve the quality, effectiveness, and efficiency of care provided to people with cancer.
PI: Ashley Rosko, MD
- Pilot an electronic comprehensive geriatric assessment (eCGA) to measure fitness in pre-AHSCT myeloma patients
- To determine the ability of p16 expression in peripheral blood T- lymphocytes to measure patient fitness and predict return to function post-AHSCT
Clinical Trials for Multiple Myeloma
(OSU-13128) Phase I/II Study of Lenalidomide in Combination With Anti-PD-1 monoclonal antibody CT-011 in Patients With Relapsed/Refractory Multiple Myeloma
PI: Yvonne Efebera, MD
- Determine maximum tolerated dose (MTD), safety and efficacy of CT-011 (pidilizumab) in combination with lenalidomide (Revlimid), and assess effectiveness in terms of overall response rate in patients with relapsed/refractory multiple myeloma
(OSU-13192) A Multicenter, Randomized, Open-Label, Phase II Study of Carfilzomib With or Without ARRY-520 in Patients With Advanced Multiple Myeloma
PI: Craig Hofmeister, MD
- Determine the effectiveness of both single-agent carfilzomib and carfilzomib plus the investigational study drug filanesib in treating patients with advanced multiple myeloma
Allow patients to cross over from single-agent carfilzomib to carfilzomib + filanesib if disease progression occurs
Recent Clinical Research Accomplishments
Circulating miRNA Markers Show Promise as New Prognosticators for Multiple Myeloma. One approach to improving risk prognostication in patients with multiple myeloma (MM) MM is to use new technologies to stratify them based on distinct outcomes. There is evidence that small non-coding RNAs, or microRNAs (miR), are involved in MM pathogenesis, but their predictive role needs to be evaluated. An international study co-led by the OSUCCC – James showed that circulating miR-16 and miR-25 are independent prognosticators of overall survival more than progression-free survival in newly diagnosed MM. Researchers aim to validate these biomarkers for use with the International Staging System to better stratify patients. This study was published in the journal Leukemia.
Modified Treatment Regimen Reduces Side Effects for Multiple Myeloma Patient. A phase II study at the OSUCCC – James found that adding the drug aprepitant to the treatment regimen for multiple myeloma (MM) patients receiving high-dose melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT) resulted in low rates of delayed nausea/vomiting associated with this treatment. Because of this study, which involved 26 MM patients age 18 or older undergoing high-dose melphalan followed by PBSCT, the use of aprepitant has become standard practice for these patients at the OSUCCC – James. This study was published in the journal Support Cancer Care.
Phase I Study Shows Antibody as Safe and Effective in Multiple Myeloma Treatment. Natural killer (NK) cells in the body’s immune system work to destroy multiple myeloma (MM) cells, but MM cells can evade this process by producing molecules with killer immunoglobulin-like receptors (KIRs) to inhibit NK cells. However, a phase I study at the OSUCCC – James that involved 32 patients with relapsed or treatment-resistant MM demonstrated that an anti-KIR antibody called IPH2101 is safe, tolerable and effective, thus warranting further development. This study was published in the journal Blood.
Translational Research Accomplishments
Form of Immune Therapy Might Be Effective For Multiple Myeloma. A preclinical study by OSUCCC – James researchers provided evidence that genetically modifying immune cells might effectively treat multiple myeloma. They grew the modified cells in the lab to increase their numbers and then injected them into an animal model, where they again killed human myeloma cells. “Our study presents a novel strategy for treating this disease, and we hope to bring it to patients as part of a phase I clinical trial,” says co-principal investigator (PI) Craig Hofmeister, MD, MPH. Jianhua Yu, PhD, was co-PI. The findings were published in the journal Clinical Cancer Research.
Study Identifies Key Molecules in Multiple Myeloma. OSUCCC – James researchers linked three molecules to a critical tumor-suppressor gene that is often turned off in multiple myeloma. The researchers believe their findings might offer a new strategy for treating this disease and other blood cancers. The study, published in the journal Cancer Cell, suggests that reactivating these three molecules triggers expression of the P53 tumor-suppressor gene. This, in turn, slows the growth and leads to the death of myeloma cells. Carlo Croce, MD, was principal investigator.
Elotuzumab Directly Enhances NK Cell Cytotoxicity Against Myeloma Via CS1 Ligation: Evidence for Augmented NK Cell Function Complementing ADCC. Elotuzumab is a monoclonal antibody being developed for treating multiple myeloma (MM) by targeting CS1, a cell surface glycoprotein expressed on MM cells. In preclinical models, elotuzumab showed anti-MM efficacy via natural killer (NK)-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In this study, researchers at the OSUCCC – James found that elotuzumab has additional mechanisms of action via ligation of CS1 on NK cells that complement ADCC activity. Their data suggest that elotuzumab may enhance NK cell function directly and confer anti-MM efficacy by means beyond ADCC alone. This study was published in the journal Cancer Immunology, Immunotherapy.