PET‐adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH‐05 trial

Abstract

Summary The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I–IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3‐negative patients received no further therapy. PET3‐positive patients received three additional cycles of ABVD plus involved‐field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re‐evaluated by PET scan (PET6). Study endpoints were 3‐year progression‐free survival (PFS) and overall survival (OS) rates. Two hundred and thirty‐nine patients with early‐stage and 138 with advanced‐stage were evaluable. Overall, 260 patients (70%) were PET3‐negative and had higher 3‐year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3‐positive patients. All PET3‐negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90–91%; P = 0·76) and OS (97–99%). The only independent prognostic factor for PFS was PET3‐negativity (Hazard ratio 3·8; 95% confidence interval 2·4–6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.

PET/CT Imaging of Lymphoma Outside the Western World

“…When comparing the results of LH-05 with our previous clinical trial (LH-96) (17) there was no difference in EFS and OS at 5 years but in LH-05 only 31% received more than 3 cycles of ABVD and IFRT compared to 61% and 100% in LH-96, thus demonstrating that an iPET adapted approach reduces exposure to chemo and radiotherapy without compromising the long-term treatment outcome.…”

“…601 HL patients were enrolled: 316 had stage III-IV and 285 were favorable patients, 60 (15%) of this latter (15%) were slow-responders. The 5-years event-free survival (EFS) of patients entering CR after 3 cycles of ABVD in the favorable group was significantly higher (89%) with respect to the slow responders (66%) and to the advanced-stage group (72%; P < .001) treated with 6 ABVD courses +/-IFRT (17).…”

“…After this first experience demonstrating the prognostic relevance of an early complete remission, and thanks to the scientific evidence of the very good outcome of ABVD-treated patients in HL with a negative interim PET and the possibility to easily access PET/CT scanning in Argentina, in 2005 GATLA launched the first PET adapted trial in HL patients, the LH-05 trial (17). This was a prospective, phase 2, non-randomized study conducted in 17 clinical sites in Argentina enrolling adult patients with newly classic HL.…”

Prognostic significance of interim PET/CT response for the treatment of advanced-stage marginal zone lymphoma in the post-rituximab era

“…The clinical significance of fluorine-18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in the diagnosis or management of lymphoma is gradually becoming important 1 , 2 . Although it remains controversial, several previous studies reported that the interim PET/CT response could predict long-term clinical outcomes in cases of Hodgkin lymphoma (HL), aggressive non-Hodgkin lymphoma (NHL), and follicular lymphoma 3 – 5 . However, the role of 18 F-FDG PET/CT assessment in indolent lymphomas other than follicular lymphoma is unclear due to variable 18 F-FDG avidity 6 .…”

“…Although it remains controversial, several previous studies reported that the interim PET/CT response could predict long-term clinical outcomes in cases of Hodgkin lymphoma (HL), aggressive non-Hodgkin lymphoma (NHL), and follicular lymphoma [3][4][5] . However, the role of 18 F-FDG PET/CT assessment in indolent lymphomas other than follicular lymphoma is unclear due to variable 18 F-FDG avidity 6 .…”