PET-CT Adapted Therapy after 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Interim Analysis. Preliminary Results in 102 Patients

Abstract

Background: ABVD (Doxorrubicin, Bleomycin, Vinblastine, Dacarbazine) can be considered as first line treatment for Hodgkin Lymphoma (HL). Our cooperative group has an experience of 584 patients treated with 3 or 6 cycles plus involved field radiotherapy (IFRT) with a complete remission (CR) of 91% and an event free survival and overall survival at 60 months of 79% and 95%. The new recommendations by B. Cheson define CR for HL as the lack of signs and symptoms of lymphoma with a negative PET-CT. (B Cheson et al, JCO: 25-579-586, 2007). A negative PET-CT either early during treatment of ABVD or after completion of it, has also shown to be a powerful prognostic tool (Hutchings: Blood 2006, Gallamini: Haematologica 2006). In an attempt to maintain high rate of CR and to reduce toxicity due to chemotherapy and radiotherapy we have conducted a trial with PET–CT adapted therapy. Aims: Test the feasibility and efficacy of treatment to all stages of HL adjusted to PET-CT results after 3 cycles of ABVD. Evaluate the outcome of patients who have a negative PET scan after three cycles of ABVD and receive no further treatment. Offer more intense therapy to patients who have persistent hypermetabolic lesions in PET-CT after 3 cycles of ABVD. Method: Since October 2005, 123 newly diagnosed patients with HL have been included in a prospective multicenter trial. One hundred and two have already finished treatment. Initially all patients received 3 cycles of ABVD. After the third cycle, patients were evaluated with a PET-CT. Those patients who achieved CR with a negative PET-CT received no further treatment. Patients with partial response (PR) completed 6 cycles of ABVD and IFRT on PET-CT positive areas. Those patients with less than PR after 3 cycles received high doses of chemotherapy and an autologous stem cell transplant (ASCT). All patients were reevaluated at the end of treatment. The median age at diagnosis was 33 years. Eighty-two patients (80%) had localized stage at diagnosis (I–II) and 20 (20%) presented with advanced stage (III–IV). Fifty-one (55%) patients had IPI 0–1, 37 (40%) had IPI 2–3 and 5 (5%) patients had IPI 4–5. Sixteen (16%) patients had bulky disease at diagnosis. Results. All patients completed treatment as planned. Eighty-seven (85%) achieved CR with negative PET-TC after the first 3 cycles of ABVD. Fifteen were PET positive, one with PD who achieved CR after ESHAP and ASCT. The other 14 patients completed 6 cycles of ABVD + RT. Twelve achieved CR and 2 PR. One died of progressive disease and the other one is in CR after third line treatment. Six patients relapsed, 4 are in second CR, and 2 are currently under treatment. Five of these 6 patients had achieved CR after 3 cycles of ABVD and 1 had progressive disease in PET–TC after the third cycle of treatment and received ESHAP and ASCT. With a median follow up of 17 months, 95 (93%) are in first CR, 4 (4%) in second CR and 2 in treatment. The event free survival and overall survival at 18 months are 92% and 100%. Conclusion: Treating patients with ABVD, evaluating response after 3 cycles with PET-CT, and adapting further therapy, leads to a high rate of CR avoiding potential long-term toxicity due to more aggressive chemotherapy and radiotherapy. Three courses of ABVD without radiation are adequate in patients with early CR defined by negative PET-CT. In early positive PET-CT, it is possible to intensify therapy improving the otherwise bad prognosis. These results need to be confirmed by a larger group of patients and a longer follow-up.