By John C. Byrd, MD
2009-07-01
Dr. Byrd indicated no relevant conflicts of interest.
Martin P, Chadburn A, Christos P et al. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol. 2009;27:1209-13.
For many years prior to immunophenotyping and detailed molecular
characterization, mantle-cell lymphoma was identified as an indolent
lymphoma and treated according to the paradigm of treatment
intervention only when symptoms develop. The watch-and-wait paradigm
for treatment of low-grade lymphoma is derived from many clinical
trials demonstrating no benefit in terms of survival with early
intervention. This contrasts with more aggressive lymphomas, in which
treatment cures a subset of patients and improves survival.
Identification of mantle-cell lymphoma as a distinct molecular
diagnosis was followed by clinical studies, noting relatively short
overall survival times as compared to other types of low-grade
lymphoma. Mantle-cell lymphoma was re-classified as an aggressive
lymphoma with many adapting an approach of treating the disease early,
often with very aggressive therapies. Unfortunately, current treatment
of mantle-cell lymphoma, including very aggressive approaches, still
does not cure the disease. Breaking from this newly established
paradigm of early treatment of mantle-cell lymphoma is challenging,
however, since it has been adapted by many in practice and no published
studies document the safety of the “old” watch-and-wait approach.
In this regard, Martin, Leonard, and colleagues from Weill Cornell
Medical College – New York Presbyterian Hospital have reviewed their
institutional experience, which includes a treatment philosophy of
watching asymptomatic mantle-cell lymphoma patients without therapy
until disease symptoms develop. They identified approximately a third
of patients who could be managed in this manner with a subset not
requiring therapy for a year or more. Examining clinical parameters, no
measure of harm to this patient population was noted. Indeed, the
asymptomatic group of patients had a significantly better survival rate
than patients who were treated immediately. Many limitations arise from
this trial, including the retrospective design and lack of
randomization between early and delayed treatment that would allow
definitive determination of the ideal treatment approach for this
patient population. Given the low frequency of mantle-cell lymphoma and
the small subset of patients who are asymptomatic, such a trial will
likely never be performed.
This paper is very important because it provides
published evidence that it is acceptable to monitor asymptomatic
mantle-cell lymphoma patients without institution of therapy. For the
asymptomatic patients with mantle-cell lymphoma, close observation
without therapy can be viewed as an acceptable treatment choice based
upon these data and lack of survival advantage or cure with currently
available therapy.
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