The National Comprehensive Cancer Network (NCCN) recently updated its guidelines for non-Hodgkin's lymphoma (NHL) to include
new therapeutic options, as well as changes to diagnostic criteria and staging. NHL encompasses a large group of cancers of
the immune system that can strike at almost any age. Generally speaking, NHL is much less predictable than Hodgkin's lymphoma
and has a higher tendency to disseminate to extranodal sites.
NHL has been one of the most rapidly increasing types of cancer in the past few decades, and it is estimated that more than
63,000 new cases of NHL will be diagnosed in the United States in 2007. The increase is only partly explained by the concomitant
development of NHL in the setting of HIV infection. Although NHL can manifest as several different types, it is generally
classified as either T-cell or B-cell NHL.
The more common type, B-cell NHL, includes Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic
large cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma. T-cell NHLs include mycosis fungoides,
anaplastic large cell lymphoma, and precursor T-lymphoblastic lymphoma. Prognosis and treatment of NHL depend on the stage
and type of disease.
The updated guidelines from NCCN include new recommendations for peripheral T-cell lymphomas (TCEL-1)—particularly aggressive
NHLs. In addition, the NCCN panel added guidelines for mycosis fungoides and Sezary syndrome, which are otherwise known as
cutaneous T-cell lymphomas (CTCLs). Cutaneous disease typically progresses from an indolent eczematous patch covering less
than 10% of the body surface to severe tumors that undergo necrotic ulceration and subsequent generalized erythroderma. Patients
with stage III through stage IV CTCL disease have a median survival of less than five years. Fortunately, however, CTCL patients now have a new treatment option available with the approval of Merck's vorinostat (Zolinza).
Vorinostat is a member of a relatively new class of agents known as the histone deacetylase (HDAC) inhibitors, which modulate
the expression of genes by causing an increase in histone acetylation and ultimately induce cancer cell death. Interestingly,
the well-known antiepileptic drug valproic acid (VPA) has also been shown to be a class I selective HDAC inhibitor, and there
have been some recent studies to evaluate its efficacy in chemotherapy regimens. Vorinostat was approved in 2006 for the treatment
of cutaneous manifestations in patients with progressive, persistent, or recurrent CTCL.
"Vorinostat is a welcome addition to the treatment armamentarium for CTCL, and patients are pleased that they only need to
take one dose by mouth daily," said Nermin Boles-Attia, pharmacy supervisor at The University Hospital in Newark, N.J. Healthcare
practitioners should be aware that vorinostat can increase the risk of developing deep vein thrombosis and pulmonary embolism.
In addition, severe thrombocytopenia and gastrointestinal bleeding have been reported with concomitant use of vorinostat and
other HDAC inhibitors. Therefore, it is recommended that platelet counts be monitored every two weeks during the first two
months of treatment with vorinostat.
Another change to the NHL guidelines is the addition of alemtuzumab (Campath, Genzyme), an anti-CD52 humanized monoclonal
antibody, as a first-line therapy option for certain patients with chronic lymphocytic leukemia (CLL) and small lymphocytic
lymphoma (SLL). Specifically, patients with the 17-p mutation are eligible for first-line treatment with alemtuzumab, which
is approved for the treatment of relapsed and refractory CLL.
For patients without the mutation, rituximab (Rituxan, Genentech/Biogen Idec) was added to first-line therapy options in combination
with chlorambucil (Leukeran, GlaxoSmithKline), cyclophosphamide, or CVP (cyclophosphamide, vincristine, and prednisone). Fludarabine
with or without rituximab is still considered appropriate for first-line therapy of CLL/SLL. Rituximab was also added as an
option for relapsed or refractory diffuse large B-cell lymphoma when used as part of a combination regimen.
With regard to diagnostic testing, the NCCN panel recommended that hepatitis B testing be included as part of the "essential"
workup obtained in all patients with B-cell lymphomas. This comes largely as a result of findings that patients with B-cell
NHL, but not those with T-cell NHL, have a higher prevalence of hepatitis B virus infection when compared with those who have
other cancers.
To view the updated NCCN NHL guidelines in their entirety, go to http://www.nccn.org/.
Practice Tools
