Adding Immunotherapy to Chemotherapy Benefits Patients With Various Types of NHL

June 5, 2004

Three new studies suggest that adding rituximab (Rituxan), a monoclonal antibody therapy, to chemotherapy is an effective treatment for several types of non-Hodgkin lymphoma (NHL). Monoclonal antibodies are laboratory-made substances that recognize and attach to specific proteins (called antigens) on the outside of lymphocytes (white blood cells). Rituximab binds to an antigen on lymphoma cells called CD20. Researchers think that this action helps the body's immune system destroy the cancer cells.

In the first study, researchers found that two years of maintenance therapy with rituximab increases the time it takes for the cancer to progress after chemotherapy in patients with advanced indolent lymphoma. Indolent lymphoma is a slow-growing cancer that initially responds well to therapy, but eventually recurs in most patients. Maintenance therapy is given after chemotherapy to "maintain" a tumor's response to that drug and keep the cancer from returning.

"We had hoped to see an improvement in time to progression, and the effect was even more robust than we hoped," said Howard Hochster, MD, lead author of the study and Professor of Medicine at New York University School of Medicine. In fact, the results were so good, the study was stopped early so that all patients could receive rituximab.

In this phase III clinical trial, 149 patients with stage III or IV follicular and small lymphocytic lymphoma received chemotherapy, and 154 patients received chemotherapy followed by rituximab treatment. The chemotherapy regimen used in this trial was CVP (cyclophosphamide, vincristine, and prednisone).

After two years, cancer did not progress in 74% of the patients who received rituximab, compared with 42% of the patients who received only chemotherapy. After four years, cancer did not progress in 58% of the patients who received rituximab, compared with 34% of the patients in the other group. These differences did not appear to be related to tumor cell type (histology), the presence of cancer left behind after chemotherapy (residual disease), or the amount of cancer in the patient's body (tumor burden).

"We hope this will eventually translate into improved survival in this disease. No treatment to date has shown survival improvement in indolent lymphoma," said Dr. Hochster. Because these tumors grow slowly, Dr. Hochster estimated that another five years of follow up might be necessary to know whether this therapy increases overall survival.

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In another trial, researchers found that adding rituximab to chemotherapy improves survival in younger patients with low-risk diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma. The usual treatment for DLBCL is chemotherapy based on a chemotherapy regimen called CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab added to chemotherapy has already been shown to be an effective treatment in patients over age 60, so this trial was designed to learn if rituximab would have a similar benefit in younger patients with DLBCL.

More than 700 patients aged 18 to 60 with low-risk DLBCL who had not yet been treated were randomized into two groups: half received CHOP-like chemotherapy and the other half received CHOP-like chemotherapy and rituximab. These results were observed at 15 months:

• More patients who received chemotherapy plus rituximab continued to respond to their treatment (84%), compared with those who received only chemotherapy (63%).



• Eighty-five percent (85%) of the patients who received both chemotherapy and rituximab experienced a complete remission (CR), compared with 66% of the patients who received only chemotherapy.



• Of the patients treated with chemotherapy and rituximab, cancer in 6.3% of the patients progressed, compared with cancer in 17.7% of the patients treated with chemotherapy alone.



• Overall survival was 98.5% in the patients who received chemotherapy plus rituximab, and 92% in those who received chemotherapy alone.

Because these younger, low-risk patients start with a relatively good prognosis (chance of recovery), the investigators were surprised that they were able to improve the results in these patients. "The combination of a CHOP-like chemotherapy with rituximab has achieved the best results reported ever for young patients with low-risk aggressive lymphoma," said the study's lead author Michael Pfreundschuh, MD, Director of Medical Oncology at Saarland University Medical School in Homburg, Germany. If doctors continue to see positive results in the next several years, Dr. Pfreundschuh speculates that lymphoma in this set of younger patients could be considered curable.

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In the third study involving lymphoma, investigators found that adding rituximab to chemotherapy can slow the progression of mantle cell lymphoma (MCL). This subtype of non-Hodgkin lymphoma is most common in people over the age of 60 and does not often respond to treatment.

This study included 122 patients with newly diagnosed MCL. Sixty patients received CHOP chemotherapy and 62 patients received CHOP plus rituximab.

• Thirty-four percent (34%) of the patients who received CHOP plus rituximab experienced a complete remission (CR) compared with only 7% of the patients who received CHOP.



• Ninety-four percent (94%) of the patients who received CHOP plus rituximab experienced either a CR or a partial remission (PR) compared with 75% of the people who received CHOP alone.



• The time until the treatment stopped being effective was 22 months for the patients taking CHOP plus rituximab compared with 14 months for the patients receiving CHOP alone.



• There was no significant difference in treatment-associated side effects.

"Combining immunotherapy and chemotherapy may represent the new gold standard for treating MCL," said one of the study's lead authors, Martin Dreyling, MD, of the University of Munich in Germany. "Whereas rituximab alone has limited activity against MCL, combining it with chemotherapy improves treatment effectiveness considerably without any clinically significant increase in toxicity."

What This Means For Patients

These studies show that adding the monoclonal antibody therapy rituximab to current therapies is effective in treating patients of various ages, subtypes, and stages of non-Hodgkin lymphoma (NHL). The first study shows that rituximab is an effective maintenance therapy for people with indolent NHL. The second study shows that adding rituximab to chemotherapy improves survival in young, low-risk people with DLBCL. Finally, the third study demonstrates that adding rituximab to chemotherapy slows the progression of cancer in people with MCL. In each case, doctors will continue to study the long-term treatment response and side effects of rituximab.