Surreal illustration of bone marrow landscape focusing on myeloma cells.

Myeloma Relapse Prediction: How a Revised Staging System Can Help

Jordan Keane in Health & Wellness December 2025 • 4 min read.

"Understand the Revised International Staging System (R-ISS) and its crucial role in predicting early relapse after autologous transplantation for multiple myeloma."

Multiple myeloma (MM) is a cancer of plasma cells, a type of white blood cell found in bone marrow. Over the past two decades, treatments for multiple myeloma have significantly improved, largely due to the incorporation of novel anti-myeloma agents like proteasome inhibitors and immunomodulatory drugs into induction therapy followed by high-dose therapy and autologous hematopoietic cell transplant (AHCT). Despite these advances, predicting which patients will experience early relapse after AHCT remains a challenge.

Early relapse, defined as relapse occurring within 24 months of AHCT, is a critical factor in determining a patient's overall survival. Patients who relapse early often have poorer outcomes, highlighting the need for reliable methods to predict and manage this risk. Identifying prognostic factors that can improve risk stratification and therapeutic decision-making is essential to ensure the best possible outcomes for patients with multiple myeloma.

The Revised International Staging System (R-ISS) is a tool developed to provide a more accurate prognostic model for newly diagnosed MM. The R-ISS integrates factors such as International Staging System (ISS) stage, serum lactate dehydrogenase (LDH) levels, and high-risk cytogenetics. This system aims to categorize patients into different risk groups, helping clinicians to tailor treatment strategies based on individual risk profiles.

What is the Revised International Staging System (R-ISS) and Why Does It Matter?

Surreal illustration of bone marrow landscape focusing on myeloma cells.

The Revised International Staging System (R-ISS) refines the original International Staging System (ISS) by incorporating genetic markers and lactate dehydrogenase (LDH) levels, providing a more nuanced assessment of risk in multiple myeloma patients. This enhanced staging system is crucial for predicting patient outcomes, especially the likelihood of early relapse after autologous hematopoietic cell transplantation (AHCT).

A recent study investigated the effectiveness of the R-ISS in predicting early relapse and its impact on post-relapse survival. The study leveraged data from the Center for International Blood and Marrow Transplant Research (CIBMTR), identifying 628 multiple myeloma patients who underwent their first AHCT within 18 months of diagnosis and had available R-ISS staging information at the time of diagnosis.

R-ISS Stage I: Patients in this group experienced a 23% cumulative incidence of early relapse.
R-ISS Stage II: This group saw a 39% cumulative incidence of early relapse.
R-ISS Stage III: Patients in the highest-risk group had a 50% cumulative incidence of early relapse.

The study also found that patients with higher R-ISS stages (II and III) had significantly shorter progression-free survival (PFS) and overall survival (OS). Moreover, the R-ISS stage was independently predictive of post-relapse overall survival, indicating its value in assessing prognosis even after relapse occurs. Additional factors such as a comorbidity index of ≥3 and the use of ≥2 induction chemotherapy lines were also associated with poorer post-relapse outcomes.

The Future of Myeloma Treatment: Personalization and Prevention

The R-ISS is a valuable tool for stratifying risk and predicting outcomes in multiple myeloma, its role in personalizing treatment plans is still evolving. Future research should focus on integrating the R-ISS with other emerging biomarkers and treatment modalities to further refine risk assessment and therapeutic strategies. By combining the R-ISS with novel therapies and preventative measures, clinicians can strive to improve the lives of patients with multiple myeloma, even in the face of early relapse.

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Everything You Need To Know

What is the Revised International Staging System (R-ISS), and why is it used in multiple myeloma?

The Revised International Staging System (R-ISS) is an updated version of the International Staging System (ISS) used for multiple myeloma. It improves risk assessment by including genetic markers and serum lactate dehydrogenase (LDH) levels in addition to the factors considered in the original ISS. The R-ISS matters because it provides a more accurate way to predict how patients will respond to treatment, especially in terms of early relapse after autologous hematopoietic cell transplantation (AHCT). This allows doctors to tailor treatment plans based on a patient's specific risk profile, with the goal of improving outcomes.

What does 'early relapse' mean in the context of multiple myeloma, and why is it so important to predict?

Early relapse, in the context of multiple myeloma, refers to the cancer returning within 24 months after autologous hematopoietic cell transplantation (AHCT). Early relapse is a critical concern because patients who experience it tend to have poorer overall survival rates. Being able to predict early relapse using tools like the Revised International Staging System (R-ISS) is important because it allows for more proactive and personalized treatment strategies to improve the patient's chances of survival after relapse. The R-ISS stage has been shown to be independently predictive of post-relapse overall survival.

What is autologous hematopoietic cell transplantation (AHCT), and how does it relate to multiple myeloma treatment?

Autologous hematopoietic cell transplantation (AHCT) is a procedure where a patient's own stem cells are collected and then re-infused after they receive high-dose chemotherapy. In the context of multiple myeloma, AHCT is used to help extend remission after initial treatment with novel anti-myeloma agents like proteasome inhibitors and immunomodulatory drugs. While AHCT can be very effective, predicting who will relapse early after the transplant remains a challenge. Tools like the Revised International Staging System (R-ISS) help to identify those at higher risk of early relapse so that doctors can consider additional or alternative treatments.

How does the Revised International Staging System (R-ISS) categorize patients, and what does that tell doctors about their risk?

The Revised International Staging System (R-ISS) categorizes patients into different risk groups based on factors such as International Staging System (ISS) stage, serum lactate dehydrogenase (LDH) levels, and high-risk cytogenetics. For example, R-ISS Stage I patients have a lower cumulative incidence of early relapse compared to R-ISS Stage III patients, who are in the highest-risk group. Knowing a patient's R-ISS stage helps doctors estimate the likelihood of early relapse after autologous hematopoietic cell transplantation (AHCT) and adjust treatment strategies accordingly to improve outcomes.

Are there other factors besides the Revised International Staging System (R-ISS) that are important for predicting outcomes in multiple myeloma?

While the Revised International Staging System (R-ISS) is a valuable tool for predicting outcomes in multiple myeloma, it's not the only factor that influences a patient's prognosis. Other considerations include the patient's overall health and comorbidity index, the specific induction chemotherapy regimen used, and the presence of other biomarkers. Future research aims to integrate the R-ISS with these emerging factors to create even more refined risk assessment and treatment strategies. It has been shown that a comorbidity index of ≥3 and the use of ≥2 induction chemotherapy lines are also associated with poorer post-relapse outcomes.