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Watchful Waiting & Monitoring Indolent Lymphomas

Last update: 01/16/2014

TOPICS

About Watchful Waiting | Rationale for Observation (summary) | Related Articles

Topic Search: PubMed 

Watch and wait is sometimes called "expectant management."  It has been described as  "careful observation without initiation of therapy." 1  and it is often recommended for indolent lymphoma.

See also Monitoring Lymphomas

In the News

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* BMC, 2013: Has the time to come to leave the “watch-and-wait” -
observation strategy in newly diagnosed asymptomatic follicular lymphoma patients?
 http://bit.ly/13TUmht
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ASH Education, 2012: Is there a role for "watch and wait" in follicular lymphoma
in the rituximab era? by Dr. Brad Kahl 

About Watchful Waiting

When you have an indolent (slow growing) lymphoma that is not causing symptoms (such as fatigue) or is not putting you in danger, your doctor might recommend watchful waiting, even when the disease is at an advanced stage. 

One reason your doctor might recommend observation is that the indolent lymphomas can remain stable for long periods of time, and sometimes regress spontaneously

In other words, your quality of life can be very good when you have an advanced indolent lymphoma and there is no proven advantage in the long term to treating an indolent lymphoma as soon as possible.

Further, there have been case reports of indolent lymphomas remaining stable for as long as twenty years,  but it should be noted that most patients will receive first treatment within 1 to 3 years after diagnosis.

"For all 44 "deferred" patients, the median time before requiring treatment was 31 months, and there have been 19 patients who have not yet required therapy for periods of 3 to 104 months.1

How much comfort we have with observation varies among patients.  Some of us refer to it as  "watch and worry"; other find it comforting that we can live well and long with an indolent lymphoma as a "chronic" disease.   See for a recent patient account: Story: Barbara on W&W for MALT

(As physician do with diabetes for example - managing it with medication over time, but not trying to cure it.)

Indolent lymphomas are often responsive (sensitive) to standard treatments, but at this time they are not considered reliably curable* with aggressive approaches. So this is another reason to monitor the disease and to treat only when the condition causes symptoms or progresses to a degree that increases risk.

See also Indications of When to Treat Indolent Lymphomas  | Monitoring Lymphomas

* Indolent lymphomas are very sensitive to many types of treatments, but in the past the advanced stage (III and IV)  lymphomas were rarely cured.

While still controversial (requiring more study and longer follow up), some investigators believe that combination chemotherapy with immunotherapy may cure a small % of patients with indolent lymphomas. (See Cabinillas' presentation  

 
  http://clinicaloptions.com/Oncology/Resources/CME%20Options/NHL.aspx

EARLY STAGE FL:

"In a retrospective analysis from Stanford University, 43 patients with early-stage follicular lymphoma were identified who were observed rather than treated with immediate XRT (radiotherapy).

With a median follow-up of over 7 years, 63% of these patients had not required therapy, and the estimated survival at 10 years was 85%. ... the authors from Stanford University concluded that having no initial therapy was an acceptable approach in selected patients with early-stage follicular lymphoma.

21. Advani R, Rosenberg SA, Horning SJ: Stage I and II follicular non-Hodgkin’s lymphoma: Long-term follow-up of no initial therapy. J Clin Oncol 22:1454-1459, 2004

Hopefully, the indolent lymphoma you face will be "well-behaved" and you won't need to make a decision for many years, and that when the time to treat is at hand there will be even better therapies to make use of ... and knowledge about how to use existing treatments in better ways.

Can you watch and wait too long?

EXPERT PERSPECTIVE:

The adage of "watch and wait" has been taken to the extreme to imply a benefit of deferring on therapy for as long as possible. What it actually is meant to indicate is that it is important to wait until you identify who are the progressors from those who are not.

Once someone is determined to be a progressor, we do not have any data that holding on treatment carries any benefit.

The way I use this is to indicate that treatment should be initiated when someone has indicated that they are a progressor (the classic indications for treatment) and before they become symptomatic.

We have all seen others who have deferred on therapy too long and ended up unable to tolerate therapy because they were too sick.

Suggestion: the CLLer refusing all treatment try to be more open to hearing what is out there.

~ Furman, MD

How is the Need to Treat defined? 

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See GELF and Other Criteria

Summary:  rationale for watchful waiting (close observation)
when there are no symptoms or indications of progression

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Indolent lymphomas can remain stable for long periods of time, and sometimes regress spontaneously.   
It has been reported that  some patients never require therapy.

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Treating at diagnosis could result in treating sooner than necessary, sometimes by many years.

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Therapy can be just as effective if started when needed -- such as when symptoms begin or there's evidence of advancing disease , instead of  immediately at diagnosis.

There is no proven benefit in the long term from treating when first diagnosed.

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Treatment has side effects, which can make you feel less well and could limit future treatment options.

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It's feasible that better treatment protocols may become available when it is time to treat.

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Your doctor can use this time to judge the clinical pace of your lymphoma to help guide the choice of treatment when it is needed.  The clinical pace is estimated by comparing the baseline images with subsequent tests to see the rate of growth or stability.

NOTE: There is no standard approach to treating indolent lymphomas, but new and investigational agents may well improve the management of the disease, which is typically sensitive to many kinds of treatments. For a detailed discussion on treatment decisions, see treatment-decisions  There are now many promising investigational treatments in clinical trials to consider as well.



Related Articles:

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See also Monitoring Lymphomas
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Stage I and II Follicular Non-Hodgkin’s Lymphoma: 
Long-Term Follow-Up of No Initial Therapy
Ranjana Advani, Saul A. Rosenberg, Sandra J. Horning

http://www.jco.org/cgi/content/full/22/8/1454 


Ann Intern Med. 1979 Jan;90(1):10-3.

1) No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types.

Portlock CS, Rosenberg SA.

The question of whether initial treatment is necessary in relatively asymptomatic patients with stage III and IV non-Hodgkin's lymphomas of favorable histologic types was studied by retrospective analysis. 

Two groups of patients were studied: [1] 44 non-protocol patients, followed since 1963, in whom initial treatment was withheld until required to evaluate the pace of disease and the necessity of treatment; and [2] 112 previously untreated patients who have participated in prospectively randomized clinical trials since 1971. 

For all 44 "deferred" patients, the median time before requiring treatment was 31 months, and there have been 19 patients who have not yet required therapy for periods of 3 to 104 months. 

The median actuarial survival for all 44 patients was 121 months. At 4 years, the actuarial survival of the 44 patients with deferred treatment is 77.3%, compared with 83.2% for the 112 protocol patients (P = 0.60). 

Careful observation without initiation of therapy is an appropriate option in the management of patients with relatively asymptomatic advanced non-Hodgkin's lymphomas of favorable histologic types.

PMID: PMID: 369420

 

 
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