New and Upcoming Therapies for Lymphoma
New treatments for lymphomas largely involve the use of established chemotherapy and radiotherapy agents in combination with methods that capitalize on innate features of the immune system. Successful treatment of lymphoma must take into account the patient’s age and the role of nutrition in helping the body tolerate and recover from cytotoxic treatments.
Immunotherapy (e.g., Rituxan® [Rituximab]). B-cells, and therefore all lymphomas of B-cell origin, have a molecule on their surface known as CD20 (Maloney DG 2005). Rituxan® is an antibody designed to bind to CD20 on lymphoma cells (Plosker GL et al 2003). Upon the binding of Rituxan®, a process known as antibody-dependent cell cytotoxicity (ADCC) is initiated; this causes the immune system to destroy the lymphoma cell. Because normal B-cells also have CD20 on their cell surface, use of Rituxan® also leads to their destruction, and patients suffer from low B-cell numbers for approximately six months; however, these numbers return to normal 9 to 12 months after treatment (Plosker GL et al 2003).
In the US, Rituxan® is already available for the treatment of low-grade or follicular, relapsed NHL (Plosker GL et al 2003). Recent studies suggest that Rituxan® is also effective against diffuse large B-cell lymphoma (Nakai S et al 2005).
Chemoimmunotherapy (e.g., Rituxan® and CHOP). Recent studies have shown the use of Rituxan® in combination with CHOP chemotherapy to be more effective than CHOP chemotherapy alone in elderly patients with diffuse large B-cell lymphoma (Feugier P et al 2005). This therapy is also effective in previously untreated mantle cell lymphoma and aggressive recurrent pediatric B-cell large-cell NHL (Jetsrisuparb A et al 2005; Lenz G et al 2005). Although Rituxan® in combination with CHOP is approved in Europe for the treatment of diffuse large B-cell lymphoma (the most common aggressive form of NHL), it is yet to be approved for this use in the US (Plosker GL et al 2003).
Radioimmunotherapy. Radioimmunotherapy is the use of antibodies that target the CD20 molecule on lymphoma cells to specifically deliver the radiation required to destroy the cancer cell (DeNardo GL 2005). Two such radio-labeled antibodies to CD20 (iodine-131 tositumomab and yttrium-90 [90Y] ibritumomab tiuxetan) have been tested against NHL (Dillman RO 2003). In 2002, 90Y ibritumomab tiuxetan was approved in the US for the treatment of relapsed or refractory low-grade, follicular, or transformed lymphoma; it is commercially available as Zevalin® (Dillman RO 2003; Forero A et al 2003; Grillo-Lopez AJ 2005; Lewington V 2005; Wiseman GA et al 2005). The second radioimmunotherapy agent, I-131 tositumomab, has also been approved in the US and is commercially available as Bexxar® (Lewington V 2005).
According to a recent New York Times report, two potentially lifesaving drugs are languishing in obscurity, largely due to market forces. The drugs, Zevalin and Bexxar, have been approved by the Food and Drug Administration for the treatment of lymphoma, including non-Hodgkins lympohoma; the fifth most common cancer in the United States. But only about 10 percent of eligible patients are receiving the drugs, despite some remarkable results among those few who have been treated with them. Although patients are more likely to respond to Zevalin or Bexxar than to older, more commonly-used lymphoma treatments -- and the newer drugs are better tolerated, with fewer side effects (Riley MB 2004) -- oncologists have been slow to embrace them.
Part of the problem stems from the fact that the drugs are the first members of a promising new class of treatments, known as radioimmunotherapies. These drugs utilize cutting-edge monoclonal antibody technology to deliver radioactive particles directly to tumor cells. But, while radioactivity is the key to their effectiveness, it is also a stumbling block that has rendered many oncologists reluctant to prescribe them. Due to their radioactivity, they must be administered in a hospital setting. As a result, oncologists must abandon financial incentives they might otherwise reap for prescribing older chemotherapy drugs, and they must coordinate their efforts with additional clinicians. Patients taking the new drugs must also be monitored for changes in blood cell counts.
A single treatment may cost about $25,000. But one treatment is often all that is required to effect remission. The more common alternative -- treatment with months of chemotherapy, followed by a commonly prescribed drug, Rituxan -- costs about the same.
But Bexxar or Zevalin are often more effective at stopping the deadly disease. A recent study found the drugs offer “…impressive clinical outcomes (approximately 20%-40% complete response rates and 60%-80% overall response rates for patients with [non-Hodgkins lymphoma].” (Macklis RM 2007) Another study reported similar results. (Witzig TE et al 2007) An older study compared the newer drugs to Rituxan and found an overall response rate of “…80% for the [Zevalin] group versus 56% for the [Rituxan] group.” The same study found that 30% of Zevalin patients experienced complete remission, as opposed to 16% of patients receiving Rituxan (Witzig TE et al 2002).
Advocates worry the drugs’ makers may abandon production if physicians don’t overcome their reluctance to use them soon. They hope the as-yet-unreleased results of ongoing clinical trials, designed to assess the efficacy of the drugs among large groups of patients, may finally convince oncologists to embrace their use. According to the New York Times, some lymphoma patients have been forced to take matters into their own hands, demanding access to the drugs, often with remarkable results.
Vaccine Therapy. The use of vaccination as a treatment for lymphoma is also being investigated. Further details on vaccine therapy for lymphoma can be found in the Cancer Vaccines and Immunotherapy protocol.