How Patient Characteristics Shape Outcomes in the United States
Multiple myeloma, a complex cancer of plasma cells in the bone marrow, represents approximately 1.8% of all new cancer cases in the United States, with an estimated 36,110 Americans expected to be diagnosed in 2025 2 . While considered relatively rare, this malignancy has undergone a remarkable transformation in treatment approaches over the past two decades, leading to significantly improved survival rates. The overall five-year survival rate has now reached 62.4%, quadrupling from historical figures 2 8 .
Despite these advances, multiple myeloma remains incurable for most patients, with complex treatment patterns that vary significantly based on patient characteristics, prior therapies, and response patterns. This article explores the real-world treatment landscape of multiple myeloma in the United States, examining how patient factors influence therapeutic decisions and ultimately shape outcomes.
The management of multiple myeloma has evolved dramatically from the days of conventional chemotherapy. The introduction of proteasome inhibitors (e.g., bortezomib, carfilzomib), immunomodulatory drugs (e.g., lenalidomide, pomalidomide), and monoclonal antibodies (e.g., daratumumab, isatuximab) has fundamentally changed how we approach this disease 6 8 .
These breakthroughs have transformed multiple myeloma from a rapidly fatal disease to a manageable condition for many patients, with treatment strategies becoming increasingly personalized based on individual patient factors, disease characteristics, and response patterns.
Despite these advances, relapse remains virtually inevitable for most patients. The disease often becomes refractory to available treatments, creating complex clinical challenges. As patients move through multiple lines of therapy, their cancer cells evolve resistance mechanisms, making each subsequent relapse more difficult to treat 6 9 .
Recent real-world studies have highlighted that patients who become refractory to lenalidomide (an immunomodulatory drug) and anti-CD38 monoclonal antibodies (like daratumumab) face particularly poor outcomes, with limited treatment options available 9 .
Conventional chemotherapy with limited efficacy
Introduction of first proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide)
Second-generation proteasome inhibitors (carfilzomib) and immunomodulatory drugs (pomalidomide)
Monoclonal antibodies (daratumumab, elotuzumab), HDAC inhibitors, and CAR-T cell therapies
While randomized clinical trials provide essential evidence for treatment efficacy, they often include highly selected patient populations that may not represent the broader myeloma community. Real-world evidence helps bridge this gap by examining how treatments perform in diverse clinical settings across varied patient populations 1 3 .
Studies using databases like the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, Flatiron Health database, and National Cancer Registration and Analysis Service (NCRAS) in England provide invaluable insights into actual treatment patterns and outcomes 1 3 6 .
Real-world analyses have consistently demonstrated that outcomes vary significantly based on patient characteristics such as:
These factors collectively influence treatment decisions, tolerance to therapy, and ultimately, survival outcomes 1 9 .
A pivotal 2025 study published in Clinical Lymphoma, Myeloma and Leukemia analyzed data from the SEER-Medicare database to examine treatment patterns and outcomes in lenalidomide-refractory multiple myeloma patients with 1-3 prior lines of therapy 1 .
The researchers identified 1,297 patients diagnosed between 2014-2019 who met specific criteria:
Patients were followed from initiation of their first subsequent line of therapy after meeting eligibility criteria until death, end of Medicare enrollment, or December 31, 2020 1 .
The study revealed several important patterns in real-world treatment approaches:
| Treatment Characteristic | Finding | Implication |
|---|---|---|
| Median age | 75 years | Highlights focus on elderly population |
| Comorbidity burden | 81% had ≥1 comorbidity | Patients had complex medical needs |
| Treatment regimens | Singlet, doublet, triplet each ∼30% | No clear consensus on optimal approach |
| Most common regimens | Daratumumab-pomalidomide (15%), pomalidomide (13%), daratumumab (12%) | Anti-CD38 antibodies and newer IMiDs preferred |
| Time to next treatment | 8.5 months median | Rapid disease progression post-treatment |
The research yielded sobering insights into outcomes for this patient population:
| Prior Lines of Therapy | Median Time to Next Treatment (months) | Median Overall Survival (months) |
|---|---|---|
| 1 prior LOT | 11.0 | Not reached |
| 2 prior LOT | 8.5 | 29.3 |
| 3 prior LOT | 6.1 | Not reached |
| Overall | 8.5 | 29.3 |
The decreasing time to next treatment with each successive line of therapy illustrates the increasing aggressiveness of relapsed disease and development of treatment-resistant clones 1 .
This study highlighted that elderly patients with comorbidities and lenalidomide-refractory disease after 1-3 lines of therapy receive suboptimal regimens, have poor outcomes, and move rapidly through treatments 1 . These findings underscore the critical need for more effective treatments for this difficult-to-treat population.
Multiple myeloma research relies on sophisticated tools and reagents that enable scientists to understand disease mechanisms and develop new therapies:
| Research Tool | Function | Application in Multiple Myeloma |
|---|---|---|
| Flow cytometry | Cell analysis and sorting | Identification of plasma cell populations, minimal residual disease detection |
| Interphase FISH (iFISH) | Genetic abnormality detection | Identification of high-risk genetic features such as del(17p), t(4;14), t(14;16) |
| Next-generation sequencing | DNA/RNA analysis | Mutation profiling, clonal evolution tracking |
| ELISA and mass spectrometry | Protein quantification | Measurement of monoclonal immunoglobulins, biomarker discovery |
| Animal models | In vivo disease modeling | Preclinical drug testing, studying tumor microenvironment interactions |
| CAR-T cells | Cellular immunotherapy | Engineering immune cells to target myeloma antigens like BCMA |
| Phthalimidopyrrole | C12H8N2O2 | |
| Boc-ile-N(och3)CH3 | 87694-51-7 | C13H26N2O4 |
| 1,2-Cyclodecadiene | 4415-98-9 | C10H16 |
| 4-Propylnonan-4-ol | 5340-77-2 | C12H26O |
| 1-Phenyldecan-2-ol | C16H26O |
Recent advances in semi-automated interphase FISH (iFISH) spot scoring have shown particular promise, with validation studies demonstrating high accuracy and efficiency in detecting genetic abnormalities in multiple myeloma 5 . This technology represents an important step toward standardizing genetic risk assessment in clinical practice.
The treatment landscape continues to evolve with several promising approaches:
Treatment decisions are increasingly becoming more personalized, incorporating individual patient characteristics such as age, disease stage, genetic risk factors, and prior therapies 2 . There's also growing emphasis on achieving minimal residual disease (MRD) negativity as a treatment goal, which correlates with longer progression-free survival 2 7 .
The DETER study exemplifies this personalized approach, investigating early intervention with daratumumab in smoldering myeloma to prevent progression to active disease 7 . This proactive strategy represents a paradigm shift from watchful waiting to preemptive treatment for high-risk patients.
Significant disparities exist in multiple myeloma care and outcomes. Black Americans develop multiple myeloma at more than twice the rate of white Americans and experience higher mortality 7 .
The multiple myeloma drug market is expected to reach $33 billion by 2030 4 . This economic burden creates challenges for healthcare systems and patients alike.
A 2025 analysis revealed that medical writing bias (MWB) has increased substantially in multiple myeloma research, from 4% of papers in 2007-2008 to 44% by 2023 4 .
The real-world multiple myeloma landscape in the United States reveals both remarkable progress and persistent challenges. While novel therapies have dramatically improved outcomes, patients who become refractory to key drug classes like lenalidomide and anti-CD38 monoclonal antibodies face limited options and poor survival 9 .
The future of myeloma care lies in several promising directions:
As research continues to unravel the complexity of multiple myeloma, the integration of real-world evidence with clinical trial data will be essential to guide treatment decisions and improve outcomes for all patients affected by this challenging disease.
"The Center of Excellence for Multiple Myeloma at Mount Sinai is recognized globally as a leader in patient care and translational research. We have built the largest multiple myeloma program in New York City and one of the largest in the country. Our team is specially equipped to provide expert care. Multiple myeloma is a complex disease, and it is best treated by specialists who see myeloma patients daily and have a deep understanding of its biology."