relapsed aggressive lymphoma,
Treating relapsed DLBCL - review article
Here we provide suggestions on the subject of what to do and consider when you
have an indolent lymphoma that has relapsed. The intent is
to provide discussion points to assist with the consultation you
will have with your doctor.
There are reasons to stay positive
-- because there are many effective treatment options when
the lymphoma returns, including clinical trials. The aggressive lymphomas can
still be cured; the indolent lymphomas can be managed
Staging will also be done
with imaging tests (CT or PET and CT with PET) to see
where the lymphoma is, and how far and fast it has progressed since
the last treatment.
"While most patients with new lymphadenopathy
will have recurrent lymphoma, it is certainly not true for
is often done to see if what has recurred has changed in any significant
way from the original diagnosis. This information can be vital
to making informed treatment decisions. For example, it can help
your doctors to determine if you have high- or low-risk disease.
... Pathology experts often advise that the biopsy should be of
the largest lymph node that can be safely resected (removed surgically)
to maximize the chance of getting representative cells. A
PET scan is sometimes used to guide which node or lesion to biopsy.
Consulting your oncologist ...
and if feasible an expert for a second opinion
After you have the pathology and staging information you can begin
to make an informed decision. One important goal being to
determine if the lymphoma is high- or low-risk
disease and to choose the goal of treatment accordingly.
Prepare for consults by providing information about any symptoms in
writing, and by having all pathology and staging information at hand, particularly the
latest biopsy and imaging reports and slides, and two copies of your
questions (one for you and one for your doctor).
If possible, bring along trusted loved one to the consult.
See also Optimizing Consults
Factors that determine the approach to treatment
but are not limited to:
Responsiveness to the initial treatment
did it lead to a complete response (CR)?
The duration of
response to initial treatment
For durable responses, it is sometimes feasible to use
the same therapy.
rate before and after treatment? -
is it progressing rapidly/moderately, stable, waxing and waning?
Is the lymphoma causing symptoms
fatigue, fever, b-symptoms?
lymphoma "bulky" - any lymph nodes that are larger than 8 to
The areas of involvement -
the lymphoma in a region that could affect organ function?
If certain blood counts are
Is it responsive to initial
biologic, single agent, or low dose chemotherapy
Pathology findings and blood
test markers that my suggest high- or low-risk disease
One's age, fitness,
and general health
decisions - for a list of factors that can influence
the goal, the type, or the timing of treatment.
Two basic approaches to treating relapsed indolent lymphoma:
||Management - watch & wait,
followed by judicious use of lower-toxic biologic or targeted
and/or chemotherapy agents when treatment is indicated by symptoms,
progressing disease, poor quality of life, low blood counts,
or even patient preferences.
The general idea is to treat
a lower-risk lymphoma as a chronic
to minimize toxicity, and to keep your future options
open. However, you can change to an aggressive approach
based on the efficacy of the management approaches or based on
changes to the clinical behavior.
treatment (watch and wait)
Rituxan with or without
lenalidomide (NCCN guidelines)
Clinical trial using
Low / metronomic dosing of
chemotherapy, such as
dose oral PEP-C,
Idelalisib (an oral
On July 23, 2014, the U.S. Food and Drug Administration
(FDA) approved idelalisib (Zydelig tablets for the
treatment of patients with relapsed chronic lymphocytic
leukemia (CLL), in combination with rituximab, for whom
rituximab alone would be considered appropriate therapy
due to other co-morbidities. FDA also granted
accelerated approval to idelalisib for the treatment of
patients with relapsed follicular B-cell non-Hodgkin
lymphoma (FL) or relapsed small lymphocytic lymphoma
(SLL) who have received at least two prior systemic
One of many
Investigational agents with recent encouraging clinical reports
for indolent lymphoma
Curative Approaches / Complete and Durable Response*
Use of combination of drugs or sequential therapy
(one type of therapy followed by another) - sometimes at higher doses in order to
achieve a durable complete remission, or to cure the aggressive components of the relapsed
lymphoma (such as if a
transformed lymphoma is suspected or confirmed).
objective is to achieve a
durable response to therapy, either from personal preference, or
because the lymphoma is considered high-risk -- such as the
response to the prior therapy was very short and there has been
Examples of more aggressive
approaches (depending on prior therapy):
Bendamustine + Rituxan
(chemo-immunotherapy) with or without
maintenance Rituxan, or consolidation with
CHOP + Rituxan
with or without
maintenance Rituxan, or consolidation with
Other chemotherapy combinations + Rituxan
(chemo-immunotherapy) with or without
maintenance Rituxan, with or without consolidation with
such as CHOP-R.
Radioimmunotherapy - Zevalin
as single agent or following chemotherapy
chemotherapy with stem cell rescue (from self -
from donor - allogeneic)
- an allogeneic type depending on the availability
of a donor stem cells that are a good match.
One of many
Evidence-based best practice
Adult Non-Hodgkin’s Lymphoma ~ Best Practice
decisions - factors that can influence the goal,
type, and timing of treatments
2000: Managing Indolent Lymphomas in Relapse
Working Our Way Through a Plethora of Options
The front-line management
of stage IV indolent non-Hodgkin's lymphoma has ranged from the
watch-and-wait approach to intensive experimental regimens such
as high-dose chemotherapy and bone marrow transplant. With this
broad spectrum of regimens to choose from the decision has
become a challenging exercise for both patients and oncologists.
Fernando Cabanillas, (Chair), Sandra Horning, Mark Kaminski
and Richard Champlin
In this review of the alternative therapies a panel of three
each discuss their approach to
the management of a 49-year-old patient with
relapsed indolent follicular lymphoma.
2000: Treatment options after
relapse of indolent lymphoma
Dr Leonard, Dr. Coleman, and Dr. O'Conner
Limitations of pathology findings: The pathology reports
can have limitations. Sometimes small cleaved indolent behaves aggressively.
Sometimes mixed, large, and small cell lymphomas (sometimes called grade 2) behaves indolently.
The clinical behavior can be as important as the diagnostic tests,
which do not yet account for all factors that contribute to
how the lymphoma will behave.
Staging: A second scan at two months
following relapse could be appropriate to
estimate how clinically aggressive the lymphoma is. If the clinical behavior is indolent,
watch & wait might be recommended ...
just like many do when originally diagnosed. It's not
uncommon for a relapse to appear abruptly, but then slow down and
stabilize. It can take time to judge the true clinical
behavior of the relapsed disease.
treatment evaluations: "Specifically, assessing response
[with PET] may be useful in two possible situations: to evaluate tumor response at the end of a full course of treatment, or to predict tumor response early in the course of a prolonged treatment regimen. In the first instance, early detection of treatment failure may permit a physician to institute a second-line therapeutic approach. In the second instance, accurately predicting treatment failure may allow the physician to substitute an alternative regimen, without subjecting the patient to the toxicity of the full course.
Keep abreast of clinical trials for agents that have low toxicity
and little risk of precluding subsequent treatments. These
may be best tried when treatment is not required -- as an alternative
to watch & wait.
If the lymphoma is refractory (resistant) to
standard treatments, you might
have to consider stronger measures or novel combinations of cancer
therapies. Low dose chemo regimens like PEP-C, investigational
clinical trials and
Trials of Interest however, these are not complete lists of
protocols to consider. Be sure to consult experts in the
Know what clinical trials are available and what seems
promising and low toxic. Consult with non-treating lymphoma experts
who have intimate knowledge of your disease, treatment history,
and all available standard and emerging treatments. Educate
yourself about the potential risks and benefits of new approaches.
Honesty. It's important that patient and doctor pay attention to the
"messages," or trends of the clinical course of your
lymphoma. Waiting until you get sick or very advanced
disease can limit options and work against benefiting optimally
from some treatments.
Talk to your doctor about collecting stem cells before or after the treatments you are
considering as a further precaution and use in the future, particularly if
you have high-risk disease and stem cell rescue is an
option for you down the road because of your age and fitness.
Important note: Only your doctors
have the clinical details necessary to help you to make informed
decisions. But do not limit your horizon to the perspectives
of one doctor. It can be helpful to consult outside lymphoma experts as
do not rely on the anecdotes and theories of
See also Factors that determine the
and timing of treatment
Communicating honestly with your doctor and becoming informed about the
potential risks and benefits of all the treatments appropriate to
your diagnosis are keys to managing lymphoma and
treating it effectively in a timely manner.
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