What is the maintenance drug for myeloma? A guide to therapy

October 5, 2025 •

4 min read

Maintenance therapy significantly prolongs progression-free survival for many multiple myeloma patients after initial treatment. For many years, the primary and most recognized maintenance drug for myeloma has been lenalidomide, though personalized medicine is introducing new alternatives and combination approaches.

Quick Summary

The standard maintenance drug for multiple myeloma is lenalidomide, used to prolong remission after initial therapy like a stem cell transplant. Newer agents, including combinations, are also used based on individual risk factors, disease status, and treatment goals.

Key Points

Standard Maintenance Drug: Lenalidomide (Revlimid) is the primary maintenance drug for multiple myeloma, especially after autologous stem cell transplant.
Improved Progression-Free Survival (PFS): Lenalidomide maintenance therapy has been shown to significantly extend the period of remission, delaying disease progression.
Other Options Exist: For high-risk patients or those who can't tolerate lenalidomide, other drugs like ixazomib and daratumumab are used, sometimes in combination.
Individualized Treatment: Maintenance therapy is highly personalized, with choices based on a patient's cytogenetic risk, prior treatments, and response to therapy.
Balancing Benefits and Risks: While effective, lenalidomide carries risks like low blood counts and a small increased risk of secondary malignancies, which must be balanced against the benefit of long-term disease control.
Duration of Treatment Varies: Maintenance therapy is often continued indefinitely until disease progression, but optimal duration is still being studied, especially for those achieving deep responses like MRD negativity.

The Cornerstone of Myeloma Maintenance: Lenalidomide (Revlimid)

Lenalidomide, sold under the brand name Revlimid, has long been the standard of care for multiple myeloma maintenance therapy, particularly following an autologous stem cell transplant (ASCT). As an immunomodulatory drug (IMiD), it works by both killing myeloma cells directly and enhancing the body's immune response to target residual cancer cells. Multiple clinical trials have shown lenalidomide maintenance to be highly effective in delaying disease progression and, in many cases, improving overall survival compared to observation alone. The oral administration of lenalidomide makes it a convenient option for long-term treatment.

The Efficacy of Lenalidomide

Research has solidified lenalidomide's role in extending remission. In a landmark meta-analysis of three major clinical trials, lenalidomide maintenance after ASCT significantly prolonged both progression-free survival (PFS) and overall survival (OS) compared to placebo or observation.

Extends remission: The analysis showed that lenalidomide extended median PFS from 23.5 months to 52.8 months. At a median follow-up of nearly 80 months, the OS was significantly improved as well.
Deepens response: Many patients who are not completely free of minimal residual disease (MRD) after transplant can achieve MRD-negative status while on lenalidomide maintenance, which is associated with better outcomes.

Administration and Side Effects

Lenalidomide is typically taken orally in 28-day cycles, with dose adjustments based on individual tolerance. Maintenance often begins a few months after an ASCT and continues indefinitely until the disease progresses or side effects become unmanageable. Common side effects include:

Fatigue and weakness
Gastrointestinal issues (diarrhea, constipation, nausea)
Low blood counts (neutropenia, thrombocytopenia, anemia)
Increased risk of thromboembolism (blood clots)
An increased, albeit small, risk of secondary primary malignancies (SPMs) over time.

Other Medications and Combination Approaches

For patients with high-risk multiple myeloma (HRMM) or those who cannot tolerate lenalidomide, other options are explored. The trend is moving towards more intensive, personalized maintenance strategies.

Alternative Maintenance Agents

Ixazomib (Ninlaro): An oral proteasome inhibitor (PI) that has shown a PFS benefit in clinical trials for both transplant-eligible and non-transplant-eligible patients. It is often considered for patients with high-risk cytogenetic features.
Bortezomib (Velcade): Another proteasome inhibitor, administered as an injection, that has shown efficacy, particularly in high-risk patients. Its side effect profile, especially neuropathy, can limit its long-term use compared to oral options.
Daratumumab (Darzalex): A monoclonal antibody that targets CD38 on myeloma cells. Clinical trials have explored its use in combination with other agents, including lenalidomide, for maintenance, showing improved PFS.
Isatuximab (Sarclisa): Also an anti-CD38 monoclonal antibody, currently being investigated in combination regimens with lenalidomide for maintenance therapy.

The Rise of Doublet and Triplet Therapies

For high-risk myeloma, doublet (two-drug) and even triplet (three-drug) maintenance regimens are increasingly being considered to achieve deeper, more durable remissions. A significant development has been the use of lenalidomide combined with another agent, such as a proteasome inhibitor or a monoclonal antibody, based on a patient's specific risk factors.

Comparison of Maintenance Therapies


Feature	Lenalidomide (Revlimid)	Ixazomib (Ninlaro)	Daratumumab (Darzalex)
Drug Class	Immunomodulatory Drug (IMiD)	Proteasome Inhibitor (PI)	Monoclonal Antibody (anti-CD38)
Formulation	Oral capsule	Oral capsule	Intravenous (IV) infusion or subcutaneous injection
Mechanism	Modulates immune system, promotes myeloma cell apoptosis	Inhibits proteasomes, disrupts cell cycle	Binds to CD38 on myeloma cells, triggers immune cell activity
Standard Use	Standard of care, especially post-ASCT for all-comers	Alternative for high-risk disease	Increasingly used in combination regimens
Key Side Effects	Fatigue, neutropenia, risk of SPMs and blood clots	Neutropenia, thrombocytopenia, neuropathy	Infusion reactions, infections (pneumonia), neutropenia

The Role of Personalized Treatment and Optimal Duration

Modern myeloma treatment emphasizes customizing therapy based on a patient's individual disease characteristics. For instance, cytogenetic risk status is a major factor, with high-risk patients potentially benefiting more from bortezomib- or daratumumab-based maintenance. Response to therapy is also a key factor, with minimal residual disease (MRD) testing increasingly used to guide duration decisions. Some data suggest that patients who achieve sustained MRD negativity might be able to stop maintenance therapy earlier, but more research is needed.

The question of optimal maintenance duration remains debated. While studies show continued benefit beyond several years, this must be weighed against cumulative toxicity and a potentially increased risk of SPMs over the long term. Current consensus often suggests continuing therapy until disease progression or intolerance, allowing for ongoing disease control and symptom management.

Conclusion: Prolonging Remission with Personalized Care

For many years, the standard maintenance drug for myeloma has been lenalidomide, given its proven ability to prolong remission and, in some cases, overall survival. However, the landscape of maintenance therapy is continually evolving. Alternatives like oral ixazomib and newer antibodies such as daratumumab are emerging as viable options, especially for high-risk patients or as part of combination regimens. The decision on which therapy to use is now a personalized one, based on a patient's specific risk factors and tolerance. The ultimate goal is to achieve the longest, highest quality of life possible while minimizing side effects. Ongoing research into optimal maintenance duration and novel combinations, including isatuximab, is further refining strategies for managing this complex disease. National Comprehensive Cancer Network provides detailed guidelines and information on the latest treatment standards for multiple myeloma.

Frequently Asked Questions

Maintenance therapy is necessary because it is used to prolong remission after initial treatment, like a stem cell transplant. It suppresses any remaining cancer cells (minimal residual disease) to delay or prevent a relapse of the disease.

While lenalidomide (Revlimid) is the only drug currently approved by the FDA specifically for maintenance after an autologous stem cell transplant, other agents like ixazomib, bortezomib, and daratumumab are used, particularly for high-risk patients or as part of combination regimens.

The duration of maintenance therapy is not fixed and is often continued indefinitely until the disease progresses or side effects become unacceptable. Ongoing studies are investigating if a fixed duration might be possible for patients who achieve deep, minimal residual disease-negative remissions.

Common side effects include fatigue, diarrhea, low blood cell counts (neutropenia and thrombocytopenia), and an increased risk of blood clots. A small but increased risk of second primary malignancies is also a consideration with long-term use.

Lenalidomide is an immunomodulatory drug that works by activating the body's immune system to attack myeloma cells and also by directly promoting the death of the cancer cells. This dual mechanism helps keep the disease in check after initial treatment.

High-risk patients may receive a more intensive maintenance regimen that includes lenalidomide in combination with another agent, such as a proteasome inhibitor (like bortezomib or ixazomib) or a monoclonal antibody (like daratumumab).

Yes, some studies have shown that patients who are MRD-positive after initial therapy can convert to MRD-negative status with prolonged lenalidomide maintenance. Achieving MRD negativity is associated with improved outcomes.