Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients

This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) x2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD x2; those with unfavourable disease received ABVD x2 with ISRT or, alternatively, ABVD x4. Advanced-HL patients initially received ABVD x2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) x2 based on their international prognostic score (<= 2 or >= 3). PET-2-negative patients further received ABVD x4; PET-2-positive patients received EB x4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0.08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.