Researchers have uncovered the vital role that the immune system may play in determining the duration of remission and progression-free survival in patients with multiple myeloma, according to a recent study published by Coffey et al in Nature Communications. The new findings suggested that the immune system may be capable of recovering to a healthy state if patients’ disease was brought into deep remission through therapy.
Background
Multiple myeloma, a rare hematologic malignancy that affects about 6 to 7 per 100,000 individuals per year, may be more common in male patients than female patients and twofold more common in Black patients than White patients. In healthy individuals, plasma cells within the bone marrow help the immune system produce antibodies to fight infections. However, in patients with multiple myeloma, the plasma cells become cancerous, crowd out normal cells, and adversely impact the immune system—leading to anemia, bleeding, infections, and bone damage.
According to the American Cancer Society, almost 36,000 patients will be diagnosed with multiple myeloma in 2023, and more than 170,000 patients may be currently living with the disease.
Although overall survival rates for multiple myeloma have recently improved, there is still no established curative therapy for the disease and many aspects of it remain poorly understood. Current standard of care focuses on maintenance therapy with the immune-system modulator lenalidomide, but the optimal length of therapy is controversial.
“One hypothesis … is that there may be a subset of patients who can attain a functional cure and therefore halt maintenance therapy,” emphasized lead study author David Coffey, MD, a hematologic oncologist at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “But the challenge remains to properly identify those patients ready for treatment de-escalation. Our team’s new study was designed to address this important topic,” he noted.
Study Methods and Results
In a previous phase II clinical trial—published by Diamond et al in The Lancet Haematology—the researchers investigated the dynamics of measurable residual disease during maintenance therapy for patients with newly-diagnosed multiple myeloma following unrestricted first-line therapy.
For the new correlative study, the researchers comprehensively profiled the immune microenvironment of 23 patients with newly diagnosed multiple myeloma who were receiving treatment with lenalidomide. They then compared patients achieving measurable residual disease (MRD) negativity 1 year after treatment with those who never achieved a MRD-negative state or were unable to sustain it.
“We found a strong correlation between sustained MRD negativity and prolonged survival. In fact, patients who were treated with modern combination therapy and achieved and sustained MRD negativity for at least 2 years were highly likely to remain free from multiple myeloma 10 years later,” explained senior study author C. Ola Landgren, MD, PhD, Chief of the Division of Myeloma at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. He added that a small subset of the patients who converted from MRD negativity to MRD positivity within 1 year were 14 times more likely to experience disease progression.
To account for differences in treatment histories, the researchers also conducted a separate analysis to examine the potential impact of patients receiving high-dose chemotherapy followed by autologous stem-cell transplantation vs other treatment regimens.
Conclusions
“Our study underscores how critically important the immune system is to patients’ ability to respond favorably—and achieve remission—through current therapies for multiple myeloma. Moreover, we discovered that the immune systems of patients [with multiple myeloma] being treated with modern combination therapy could ultimately recover to resemble those of healthy bone-marrow donors if they were able to achieve and sustain MRD negativity,” Dr. Coffey highlighted.
The researchers plan to conduct further studies with a larger patient population to explore whether treatments aimed at enhancing the immune system can improve the response to existing multiple myeloma therapies, leading to improved patient outcomes overall.
“We have already launched a follow-up study designed to characterize [multiple] myeloma cell biology and host immune cell biology of patients with long-term, sustained MRD negativity [vs] patients who convert from MRD negativity to MRD positivity. Ultimately, we are seeking to understand underlying mechanisms to develop curative strategies,” Dr. Landgren concluded.
Disclosure: For full disclosures of the study authors, visit nature.com.
