The prognosis for patients with classical Hodgkin lymphoma
treated today is significantly better than it would have been 15
years ago. More than 90% of patients with early-stage disease and
80% with advanced-stage disease will be cured. Several factors may
be responsible for this: Splenectomy has been abandoned,
radiotherapy fields and doses have been lowered, very toxic
chemotherapy drugs have been eliminated from first-line therapy,
and patients with relapsed disease now benefit from stem cell
transplantation.
"While this evidence is indirect, population-based findings
provide credence to the idea that reducing the intensity of
first-line therapy has not resulted in worse overall outcomes for
patients with classical Hodgkin lymphoma, and supports increasing
efforts to minimize therapy further," said Nancy L.
Bartlett, MD, of the Siteman Cancer Center at Washington
University, St. Louis.
"But despite the overall excellent prognosis in most patients,
the optimal treatment for both early and advanced disease remains
controversial," she added. "Successful treatment must balance the
highest cure rate with primary therapy with the fewest
treatment-related complications."
Historically, overtreatment with both chemotherapy and
radiotherapy has been the rule in most patients, but some
investigators believe that toxicity can be reduced and good
outcomes maintained. Applying interim PET/CT after the first few
cycles of chemotherapy to assess response can potentially help. "If
current trials confirm the usefulness of midtreatment PET/CT
assessments, perhaps we can resolve the debate regarding 'too much'
or 'too little' therapy," she said.
Dr. Bartlett and Kristie Blum, MD, described
the state of the art in Hodgkin lymphoma at an educational session
at the 52nd American Society of Hematology (ASH) Annual Meeting,
held December 4-7 in Orlando, Florida.
Targeted Therapies
Greater understanding
of the biology of Hodgkin lymphoma and recognition of prognostic
biomarkers has led to the development of targeted therapies that
address the multiple pathways thought to be dysregulated or altered
in Hodgkin lymphoma. These targeted agents will be expensive, and
clinicians will want to use them upfront (at diagnosis), in
combinations, and possibly as maintenance therapy.
The pathways in question include NF-ĸB, PI3/AKT, mTOR, surface
receptor signaling through CD30, CD40, and RANK, and immunologic
defects through alterations in the tumor microenvironment. The
future of Hodgkin disease therapeutics, therefore, may involve
targeting multiple pathways simultaneously, according to Dr.
Blum.
Table 1 shows some of the agents in clinical development that
are selective for these pathways that may one day become accepted
therapeutic options for patients with relapsed or poor-prognosis
Hodgkin lymphoma. At this time, most of the focus is on rituximab
(Rituxan), brentuximab vedotin (SGN-35), lenalidomide (Revlimid),
and panobinostat in the front-line setting or as maintenance
therapy after autologous stem cell transplantation.
While several of these agents have significant single-agent
activity in relapsed disease, combinations are likely to be more
effective. Preclinical studies to determine which agents are
synergistic with chemotherapies or other targeted agents are
underway.
"These novel therapies should also eventually be incorporated
into front-line regimens or used as maintenance therapy, with the
aim of reducing toxicity in patients with very favorable disease
and improving outcomes in those at high risk for relapse," Dr. Blum
said. ■
