PET -CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Preliminary Results in 193 Patients

Positron emission tomography using 18F-fluoro-2-deoxy-d-glucose (FDG-PET-CT) is an important tool for treatment response assessment in Hodgkin Lymphoma (HL) treated with ABVD. It can predict response and overall outcome. The negative predictive value for PET-CT in patients (pts.) with HL is 90–94%. New recommendations define complete remission (CR) for HL as the lack of signs and symptoms of lymphoma with a negative PET-CT. OBJECTIVES: Reduce therapy in pts. who achieve early CR with negative PET-CT. Intensify treatment, only in pts. with positive PET-CT after 3 cycles of ABVD. Achieve CR, event free survival (EFS) and overall survival (OS), as good as in our historical control, when we used 3 or 6 cycles of ABVD plus involved field radio therapy (IFRT) in all pts.(LH-96) PATIENTS AND METHOD: Since October 2005, 200 newly diagnosed pts. with HL have been included in a prospective multicenter clinical trial (LH-05) All pts. received 3 cycles of ABVD and were then evaluated with a PET-CT (PET-CT +3) Pts. with a negative PET-CT+3 and absence of other signs or symptoms of lymphoma were considered in CR and received no further therapy. Pts with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions were considered in partial response (PR) and completed 6 cycles of ABVD and IFRT on PET-CT positive areas. Pts with less than PR received high doses of chemotherapy and an autologous stem cell transplant (ASCT). All pts were re-evaluated at the end of treatment with a new PET CT. One hundred and ninety three pts. have been evaluated. The median age at diagnosis was 29 years. One hundred and twenty five (65%) had localized stage (I-II) non bulky and 68 (35%) presented with advanced stage (III-IV), or bulky disease, 33 (17%) had bulky disease. RESULTS: One hundred and forty-eight (77%) achieved CR with negative PET-CT + 3. Forty-five (21%) were PET-CT+3 positive, 5 showed progressive disease. The other 40 pts. were in PR and completed a total of 6 ABVD + IFRT in PET-CT positive areas. Twenty eight achieved CR and 12 persisted with hypermetabolic lesions. Three died of progressive disease. After finishing planned treatment 178 pts. (92%) were in CR. With a median follow up of 39 months the EFS and OS at 36 months is 80% and 97% respectively. Patients with negative PET-CT +3 have an EFS of 86% compared to 61% for pts. with positive PET-CT+3 (P=0,001). We perform a multivariate analysis for EFS which included age, stage, IPS, bulky disease, extranodal areas and the result of the PET –CT+ 3. This last parameter together with age were the only ones with statistical significance (p=0.001 and 0.046 respectively). When comparing the results LH-05 with LH-96 there is no difference in EFS and OS at 36 months (83% vs. 85% and 97 vs. 96%) but in LH-05 only 23% received 6 cycles of ABVD and IFRT compared to 61% and 100% in LH-96. This reduces the exposure to chemo and radiotherapy. CONCLUSION: With PET-CT adapted therapy after 3 cycles of ABVD, 148 pts.(77%) received only 3 cycles of ABVD as initial therapy with an EFS and OS of 80% and 97% at 36 months. In the Cox regression model, PET-CT at completion of treatment was the most significant factor associated to EFS. In this interim analysis of PET-CT adapted therapy to all stages of HL, treatment with 3 cycles of ABVD can be adequate for pts. with negative PET-CT+3. Continuing with ABVD after a positive PET-CT +3 can be considered insufficient. A longer follow-up and a larger number of pts. are necessary to confirm these results.

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