Intensive Induction Is Beneficial for High Risk Younger Patients with Aggressive B-Cell Lymphoma, While Frontline ASCT Brings No Benefit: Final Analysis of MegaCHOP-BEAM and MegaCHOP-ESHAP-BEAM Studies.

Objectives. Both high-dose induction and front-line ASCT have been tested for improvement of treatment results in younger patients with aggressive lymphomas. Since 1998, Czech Lymphoma Study Group is testing these approaches in Phase II prospective studies. We present mature data from two studies conducted in the pre-Rituximab era.

Methods. In 1998–1999, patients up to 65 years of age with all types of aggressive lymphomas except Burkitt and lymphoblastic lymphoma and age-adjusted (aa)IPI 2 or 3 were recruited to MegaCHOP-BEAM protocol, which consisted of 3–4 cycles of high-dose CHOP (cyclophosphamide, 3 g/m², adriamycine, 75 mg/m², vincristine, 2 mg and prednisolone 300 mg/m² + G-CSF every two weeks) followed with BEAM and ASCT. From 2000, 3 cycles of MegaCHOP were followed with 3 cycles of ESHAP and BEAM consolidation. Peripheral blood progenitor cells were collected after 2nd or 3rd MegaCHOP in first and after 1st ESHAP in the second protocol. Analyses were performed on intention to treat principle.

Results. 21 patients were recruited to MegaCHOP-BEAM and 30 patients to MegaCHOP-ESHAP-BEAM protocol, respectively. Median age was 41 years (range, 21–66 years), 29 patients were males (57%). 47% of patients had diffuse large B-cell lymphoma (DLBCL), 33% primary mediastinal B-cell lymphoma (PMBCL), 16% peripheral T-cell lymphoma and 4% grade 3 follicular lymphoma. 53 % of patients had aaIPI 2 and 47% of patients had IPI 3. Overall response rate was 93% and 70% of patients achieved complete remission. Treatment related mortality was 4% (2 patients). 67% of patients proceeded to transplant and in 21%, protocol was changed because of toxicity. Median follow up is 63 months (range, 32–96) for living patients. Median overall survival or progression-free survival have not been reached and actuarial overall survival is 66 ± 13% in three years with no differences between the two protocols. Patients with PMBCL had better outcome than patients with DLBCL and patients of other histologies (3-year survival 94% v. 60% v. 30%, p = 0,001). Interestingly, patients with aaIPI 3 apparently benefited from addition of ESHAP (3-year survival 77% in MegaCHOP-ESHAP-BEAM v. 30% in MegaCHOP-BEAM, p = 0,03) while aaIPI 2 patients had the same survival with both protocols. Omission of ASCT or protocol change because of toxicity did not seem to influence patients outcome.

Conclusions. Full-lenght intensified induction improved treatment results in high-risk patients with aggressive B-cell lymphomas, particularly with aaIPI 3, while ASCT did not seem to have an impact. For T-cell lymphomas, other treatment strategies have to be sought.