New Treatment Approaches for Multiple Myeloma Patients

Maintaining Safe and Effective Treatment for Multiple Myeloma

In a recent interview with OncLive, Dr. Biran, associate professor of medicine at Hackensack Meridian School of Medicine, reminds healthcare professionals of the importance of continuing to use therapies for multiple myeloma patients in a much safer and effective way, quoting the struggle to reduce infections in patients. Understanding these challenges, Dr. Biran discusses current clinical trial data and treatment options for patients with multiple myeloma.

Unmet Needs in Multiple Myeloma Treatment

Multiple Myeloma is a chronic disease and, while significant advancement has been made in treatment options, patients ultimately relapse, and most of them die of their disease. One of the major unmet needs in multiple myeloma treatment is patients who are triple-class refractory, meaning they have become resistant to the most common agents: proteasome inhibitors, Immunomodulatory drugs, and anti-CD38 monoclonal antibodies.

Beyond BCMA-Directed Therapy

At this time, the unmet need is for those who have progressed after BCMA-directed therapy. In the DREAMM-7 trial, a combination of daratumumab, bortezomib, and dexamethasone (DVd) was compared to belantamab mafodotin-blmf (Blenrep) combined with bortezomib and dexamethasone for patients with early relapsed myeloma. Belantamab mafodotin is an important treatment that was previously approved by the FDA but was taken off the market because of potential lack of efficacy and toxicity. Results showed that belantamab mafodotin plus bortezomib and dexamethasone is superior to DVd, an existing standard-of-care regimen, and may abrogate high-risk features in the early relapse setting. This change in philosophy towards treatment after BCMA-directed therapy could result in approvals and novel therapies for multiple myeloma patients.

High-Risk Patients Receiving CAR T-Cell Therapy

In another study, the CARTITUDE-4 focused on functionally high-risk subset patients who relapse early after the transplant. The study evaluated ciltacabtagene autoleucel (cilta-cel; Carvykti), which is a BCMA-directed CAR T-cell therapy compared to standard-of-care regimens in functionally high-risk patients. Results showed a significant improvement in the median progression-free survival (PFS) and overall response rate with the use of cilta-cel compared with standard-of-care regimens. This change could create a roadmap for using CAR T-cell therapy early in relapse, particularly for high-risk patients.

New Treatment Regimen for Transplant-Ineligible Patients

For transplant-ineligible patients in the newly diagnosed stage, the standard of care has been the combination of daratumumab with lenalidomide and dexamethasone, but the IMROZ study compared isatuximab-irfc (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone (VRd) with VRd alone. The former proved both efficacy and feasibility in delivering a quadruplet regimen for this patient population. A proteasome inhibitor is crucial, particularly for high-risk patients who are unfit for transplantation.

Moving Forward in Treatment

As patients with multiple myeloma live longer, they are becoming more vulnerable to chronic infections due to chronic therapy, chronic steroid use, and, more specifically, the use of bispecific T-cell engagers, which dampen T-cell response and immune response. To address this, healthcare professionals may need to identify new antigen targets, such as FcRH5, while looking at fixed-duration therapy with bispecific T-cell engagers for 6 to 12 cycles or converting to a monthly dosing regimen to improve safety and effectiveness.

Originally Post From https://www.onclive.com/view/myeloma-data-presented-at-asco-highlight-continued-evolution-of-treatment-paradigm

Myeloma data presented at ASCO highlights continued evolution of treatment paradigm.