Just as symptoms of Waldenstrom macroglobulinemia (WM) vary greatly among people who have the disease, so does response to treatment and duration of response. Currently, there is no way to accurately predict how good or how long a response will be for any given individual. One of the goals of WM research is to better determine how each person will respond to a particular treatment based on their unique genetic makeup and disease biology.
How will my response to treatment be evaluated?
After receiving treatment for Waldenstrom macroglobulinemia, your doctor will assess your response based on the results of a number of tests. These will likely include a physical exam, blood tests, and CT scans of your chest, abdomen, and pelvis. Response to treatment is largely determined by your IgM level; however, it is not the only factor. Your doctor will also consider whether you have any new or worsening symptoms of WM, as symptom relief is one of the main goals of treatment.
Caution is advised in the early evaluation of treatment results since some medications can cause IgM levels to fluctuate. This makes it difficult to determine if the cancer is, or is not, responding to therapy. For instance, rituximab (Rituxan®) can cause an increase in IgM levels that is temporary (called IgM flare) and does not necessarily imply disease progression. Conversely, bortezomib (Velcade®) can cause IgM levels to decrease without actually killing the cancer cells, giving a false impression of response to treatment. And some medications simply take longer than others to lower IgM levels. Your doctor will take these factors into consideration when evaluating your response to therapy.
What are the possible responses to treatment?
Experts in Waldenstrom macroglobulinemia developed a framework to categorize how well a person with WM responds to treatment. Generally speaking, response to treatment can result in either improvement in disease status, stabilization of disease, or disease progression. These response categories are further broken down by specific criteria, as follows:
- Complete response
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- Normal IgM level
- Enlarged lymph nodes and enlarged spleen, if present at baseline, have returned to normal size
- No sign of cancer in bone marrow
- No signs or symptoms of WM
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- Very good partial response
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- IgM level reduced by 90 percent or more from baseline
- Enlarged lymph nodes and enlarged spleen, if present at baseline, have returned to normal size
- No new signs or symptoms of WM
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- Partial response
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- IgM level reduced by half or more (but less than 90 percent) from baseline
- Enlarged lymph nodes and enlarged spleen, if present at baseline, have gotten smaller
- No new signs or symptoms of WM
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- Minor response
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- IgM level reduced by less than half from baseline
- No new signs or symptoms of WM
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- Stable disease
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- IgM level stayed about the same (less than 25 percent reduction) from baseline
- Enlarged lymph nodes or enlarged spleen, if present at baseline, have stayed the same
- No new signs or symptoms of WM
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- Progressive disease
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- IgM level increased 25 percent or more from baseline, or
- The signs and symptoms of WM have gotten worse
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What happens if I don’t have a good response to treatment?
Doctors use the response categories outlined above to determine whether or not you need more treatment.
If you had a complete response to therapy no further treatment is needed. Your IgM level will be monitored at regular intervals. If your treatment regimen contained rituximab (Rituxan®), your doctor may recommend maintenance therapy with rituximab alone. This may help you stay cancer-free longer. If at some point your IgM level increases beyond the normal range, it does not mean you must start treatment. More treatment is only needed if symptoms of WM return.
If your cancer responded to treatment, but not completely (meaning you had a very good, partial, or minor response), you’ll only need more treatment if you have symptoms that haven’t improved. Changing to a different treatment regimen may be recommended. If you don’t have symptoms, no further treatment is needed. Your IgM level will be monitored at regular intervals. If you had rituximab (Rituxan®) as part of your therapy, maintenance therapy with rituximab alone may be an option.
If the cancer did not respond to treatment – meaning the disease remained about the same (stable disease) or got worse (progressive disease), changing to a different treatment regimen is recommended.
What if I feel better after treatment, but my IgM level remains high?
If you appear to be responding to treatment, but your IgM level remains high – even after the period of time when IgM levels should stop fluctuating following therapy – your doctor may order additional tests, including a bone marrow biopsy, to get more information. Although uncommon, it is possible that a slow-growing lymphoma like WM transforms into a more aggressive lymphoma, such as diffuse large B-cell lymphoma. This may occur because the cancerous WM cells acquire additional mutations over time that cause them to change.
Signs of transformation to a more fast-growing lymphoma include a change in symptoms, such as worsening fatigue, unexplained fever, night sweats, or significant weight loss. Other symptoms can include rapidly enlarging lymph nodes and organs (liver and spleen). If testing indicates that WM has transformed, there are effective treatments available for more aggressive lymphomas, but they must be started promptly.