Rituximab Benefits Younger Patients with Good-Prognosis Diffuse Large-B-Cell LymphomaKey Words
Non-Hodgkin’s lymphoma, large-B-cell lymphoma, CHOP, rituximab (Rituxan®), monoclonal antibody, targeted therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Addition of the drug rituximab (Rituxan®, a monoclonal antibody) to a standard chemotherapy regimen for diffuse large-B-cell lymphoma significantly increased survival for patients with good-prognosis disease who were younger than 60.
Source
The Lancet Oncology, published online April 5, 2006; in print May 2006 (see the journal abstract)
(Lancet Oncol. 2006 May;7(5):379-91)
Background
B-cell lymphoma is a cancer of the B cells, a type of white blood cell. As part of the immune system, normal B cells make
antibodies and help fight infections. B-cell lymphoma is the most common type of non-Hodgkin's lymphoma.
The chemotherapy regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, known as CHOP, is currently the standard treatment for B-cell lymphoma. The addition of the drug etoposide to CHOP (CHOEP) improves survival, but is more toxic than CHOP alone and is not generally used in the United States.
Rituximab is a monoclonal antibody that binds to a specific
protein (CD20) on the surface of many B cells, thus tagging those cells for destruction by the patient’s own immune system. Targeted therapies such as rituximab tend to be less toxic than other kinds of systemic treatments that affect a variety of normal tissues.
A previous study showed that the addition of rituximab to CHOP increased survival for elderly patients. The trial described here evaluated whether the addition of rituximab to CHOP, CHOEP, and related chemotherapy regimens in younger patients with good-prognosis disease provides a similar benefit.
The Study
Patients were enrolled in this phase III trial if they had untreated diffuse large-B-cell lymphoma that tested positive for CD20 (the rituximab target) and that fell into categories known to pose a low or intermediate risk of recurrence after treatment. The participants ranged in age from 16 to 60 years old.
Researchers with the trial randomly assigned participants to receive either six cycles of CHOP-like chemotherapy plus rituximab or six cycles of CHOP-like chemotherapy alone. Some participants in both groups also received radiation therapy as needed for bulky disease, following their country’s national standards.
The researchers measured the time before patients’ disease progressed (called event-free survival), as well as overall survival and toxicity of the therapy. Patients returned for follow-up every three months for the first two years and then every six months thereafter.
The trial was a cooperative effort of the MabThera International Trial (MInT) Group, with sites in Europe, Latin America, Australia, and Israel. The lead author is Michael Pfreundschuh, M.D. of the University Clinic of Saarland, in Homburg, Germany.
Results
From 2000 to 2003, investigators from 18 countries enrolled 824 patients. In November 2003, at the first planned analysis of the data before the end of the study, the difference in event-free survival between groups was significant enough for the researchers monitoring the trial to recommend that the trial be stopped early and rituximab be offered to all participants.
Five months after starting treatment, 86 percent of those patients receiving rituximab and any CHOP-like chemotherapy regimen had experienced complete remission of their cancer, compared to 68 percent of patients receiving CHOP-like chemotherapy alone.
Around the three-year mark, 79 percent of the rituximab patients were alive and had yet to see their disease progress, compared to 59 percent of the chemotherapy-only patients. Overall survival at three years was also significantly greater in patients receiving both rituximab and any CHOP-like chemotherapy (93 percent versus 84 percent).
Among patients receiving chemotherapy alone, use of the CHOEP regimen resulted in higher three-year event-free survival than use of CHOP. However, CHOEP’s advantage over CHOP disappeared with the addition of rituximab.
Finally, toxic effects were low and were about the same across all the groups, regardless of treatment.
Comments
“This is the result we would have anticipated from what we know about the biology of the disease,” says John Janik, M.D., co-director of the National Cancer Institute’s Clinical Trials Team. Clinicians now know for certain that “…rituximab works well in older patients and works equally well in younger patients.”
The MInT investigators wrote that “to our knowledge, these findings are the best reported for this group of patients to date in a randomised trial….[T]he proportion of young patients who need salvage treatment – usually high-dose chemotherapy with haemopoietic stem-cell transplantation – could be halved with the addition of rituximab.”
Janik also notes that a new chemotherapy regimen called EPOCH (etoposide, vincristine, and doxorubicin with bolus doses of cyclophosphamide and oral prednisone) plus rituximab is now being tested in clinical trials against CHOP plus rituximab. In preliminary studies, the EPOCH regimen “appears to have better impact than CHOP chemotherapy and generally eliminates the requirement for radiation in patients with bulky disease.”
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