Redefining Cure in Multiple Myeloma: Are We Chasing a Moving Target?

Area of Science:

• Hematology
• Oncology
• Immunotherapy

Background:

• Multiple myeloma (MM) is an incurable plasma cell malignancy.
• Advances in immunotherapies like CAR-T therapy and bispecific antibodies have improved outcomes but not eradicated the disease.
• Therapeutic resistance is driven by intratumoral heterogeneity and the bone marrow microenvironment.

Purpose of the Study:

• To reevaluate the concept of
• cure
• in MM, moving beyond a binary definition.
• To propose a dynamic, patient-centric model for MM management.
• To align clinical goals with biological realities and improve patient quality of life (QoL).

Main Methods:

• Review of current literature on MM pathophysiology.
• Critique of existing cytotoxic and immunomodulatory treatment paradigms.
• Exploration of emerging strategies like precision medicine, single-cell genomics, and AI-driven risk stratification.

Main Results:

• Novel immunotherapies achieve high rates of minimal residual disease (MRD) negativity.
• Relapse remains a challenge due to subclonal evolution and dormant MM clones.
• Current treatments do not fully address the biological complexities of MM.

Conclusions:

• Reframing cure as a spectrum offers a more realistic framework for MM management.
• Integrating precision medicine and QoL considerations can foster durable remissions.
• A paradigm shift is needed to embrace biological complexity and redefine success in MM therapy.