High-Dose Therapy in Mantle Cell Lymphoma

ORLANDO-High-dose therapy with stem cell support improves event-free survival in patients with mantle cell lymphoma when performed in first remission, according to results of a European Intergroup study presented at the 41st Annual Meeting of the American Society of Hematology (abstract 3572).

"Mantle cell lymphoma is one of the most challenging of the lymphomas. It exhibits an indolent histology, yet an aggressive clinical course," said Martin Dreyling, MD, University Hospital, Munich. With its short survival of 2½ to 3 years, mantle cell lymphoma resembles an aggressive NHL, but it is not curable. Many chemotherapy regimens, including interferon maintenance, can induce transient responses.

‘Dismal Clinical Course’

"The disease has a dismal clinical course uninfluenced by conventional chemotherapy with single or combined agents. New therapy options are urgently needed," he said. Recently, high-dose chemotherapy with stem cell rescue and total-body irradiation has emerged as a viable treatment option (Ketterer: Ann Oncol 8:701, 1997).

Dr. Dreyling and his colleagues from the European Mantle Cell Lymphoma Intergroup (coordinator: Professor Wolfgang Hiddemann) reported preliminary results of a prospective randomized trial to answer the key question of whether high-dose therapy with transplant is better than conventional interferon maintenance therapy in patients with mantle cell lymphoma who obtained a complete or partial remission after initial cytoreductive chemotherapy.

Dr. Dreyling noted that mantle cell lymphoma is much less sensitive to high-dose chemotherapy "if it is already relapsed. Thus, we decided to evaluate the value of high-dose chemotherapy in first-line therapy."

Centers in Belgium, France, Germany, Great Britain, Italy, the Netherlands, Spain, and Switzerland enrolled 180 patients; 147 patients had confirmed mantle cell lymphoma histology, and 130 were evaluable for response. Median patient age was 53 years.

Patients were started off with a CHOP-like regimen; 73% of the evaluable patients responded to the therapy and subsequently received either myeloablative therapy plus autologous stem cell transplantation or interferon-alfa maintenance. After two cycles of cytoreductive consolidation chemotherapy, patients randomized to interferon-alfa maintenance received a standard dose of 5 × 10⁶ units three times a week.

Patients assigned to the high-dose treatment arm were mobilized with DexaBEAM-high doses of dexamethasone, BCNU, etoposide, ara-C, and melphalan plus G-CSF-followed by stem cell retrieval. Stem cells were reinfused after high-dose chemotherapy and total body irradiation. Treatment in this study was associated with minimal complications.

Event-Free Survival

The maximum follow-up in this study was 4 years. Event-free survival was significantly higher in the transplanted patients, with 17% relapsing, compared with 35% who received interferon-alfa maintenance. Overall survival is not yet statistically different, Dr. Dreyling said.

"We are quite sure that these differences will translate into improvements in overall survival rates in mantle cell lymphoma," Dr. Dreyling concluded. "This first prospective randomized trial demonstrates a highly beneficial effect of intensive treatment. Further studies to optimize the design of high-dose therapy are clearly warranted, and second-generation trials are being planned in this poor-prognosis patient population."