Treatments for Early Relapse

Most patients with myeloma will experience periods of sustained response or remission with intermittent relapse, or progression, over the course of the disease. Based on a patient’s response to treatments, their healthcare team may consider adjustments to therapies. Therapies are typically approved, or classified, based on the number of relapses — for example, first relapse, second relapse, third relapse, and so forth. 

What Is Early Relapse?

In general, the term “early relapse” refers to the first, second or third time the myeloma stops responding to treatment. Early relapse signifies disease progression that occurs during treatment, or shortly after stopping therapy. (What is a line of therapy? One example is induction therapy followed by autologous stem cell transplant and maintenance.)  

What Does It Mean to Experience a Very Early Relapse? 

The terms “early relapse” and “very early relapse” can be confusing. In recent years, frontline therapy has improved considerably. These improvements have led to better outcomes for myeloma patients.  

Unfortunately, a small percentage of patients still relapse very early after diagnosis. For example, some may relapse as early as nine months into treatment. A patient may relapse even after receiving new and effective treatments. Very early relapse, also known as primary refractory or functional high risk, refers to the following: 

• myeloma that does not respond at all to frontline therapy. 
• myeloma that responds well to therapy initially. Yet, it progresses during or within 60 days after completing frontline therapy. This is common with high-risk disease. 
• Soon after completing or receiving their first treatment regimen, some patients may have a relapse. 

Relapse in Standard-Risk Patients

For patients with standard-risk disease, the first period of response can last 2–3 years or even longer.  

For patients who have had an autologous stem cell transplant (ASCT) followed by a remission that lasted 2-3 years or longer, a second transplant at relapse is a reasonable option. This option is possible if the patient’s stem cells are available. The pros and cons of a second ASCT versus other novel combinations must be discussed carefully with the treating physician. Management can include the following options: 

• Simply tweaking ongoing maintenance. For example, an adjustment to the dosage of Revlimid®. Another option may be adding dexamethasone (dex).  
• The patient may be directed to re-use the initial therapy if that therapy produced a remission. One example is adding Velcade and dex to Revlimid.  
• Another example is switching to a whole new regimen. 

For non-transplant patients, a first relapse may occur after a remission.  A remission is a period off therapy for at least 6 months to 1 year. The first strategy is to consider re-using the therapy that produced the remission. 

Approximately 50% of patients will experience a second remission with the same therapy that produced the first remission. This is often true for those patients whose remission lasted a year or longer. 

If a patient receiving Revlimid has a non-aggressive relapse, it may be possible to restore their response to treatment. To do so, dexamethasone and another agent may be added to the Revlimid treatment. 

What Are Drug Therapy Options for Early Relapse?

The most important step in determining how to treat your early relapse is to meet with your multiple myeloma specialist or hematologist/oncologist. 

As many myeloma specialists agree, there is no one right answer for every patient. Effective combination regimens are usually selected from the three major classes of drugs: 

• proteasome inhibitors (PIs), 
• immunomodulatory drugs (IMiDs), and 
• monoclonal antibodies (mAbs). 

The IMF's Chief Medical Office Dr. Jospeh Mikhael, MD commented on these three major classes of drugs in this article in Cancer Therapy Advisor. 

Furthermore, drugs that are currently approved for use after 1-3 prior therapies that are also used in the frontline setting include: 

• Velcade® (bortezomib), a PI 
• Revlimid® (lenalidomide), an IMiD 
• Cytoxan (cyclophosphamide), an alkylating agent, and 
• Thalomid® (thalidomide), an IMiD. 

Drugs that are approved for one or more prior lines of therapy, but are not yet approved as frontline therapy include: 

• Kyprolis® (carfilzomib), a PI 
• Darzalex® (daratumumab), a mAb 
• Empliciti® (elotuzumab), a mAb, and 
• Ninlaro® (ixazomib), a PI 
• Pomalyst® (pomalidomide), a IMiD 

Use of an effective and fast-acting therapy is essential for patients who relapse early. These kinds of therapies are especially important for those with high-risk cytogenetic abnormalities (HRCA). These HRCA are deletions and translocations of genetic material from chromosomes in myeloma cells during cell division, including t(4;14), t(14;16); t(14;20), 1q+, and 17p-). 

If not refractory to any of these treatments, the approved combinations that are effective in early relapse include: 

• Darzalex, Revlimid, and dexamethasone  
• Darzalex, Velcade, and dexamethasone  

Other three-drug combinations that are new to the patient may also be considered. Current practice is to include dexamethasone as part of the treatment regimen. 

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