Early Positron Emission Tomography Response–Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial

Abstract

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated-according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)-stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET-361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.

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

“…Interim analysis of the H10 study (Raemaekers et al , ) demonstrated a superior PFS for patients receiving involved‐nodal RT (INRT). In recently published final results, no significant difference in PFS was demonstrated between patients with EUF‐HL and negative PET‐2 who did or did not receive INRT (HR 1·45 95% CI 0·84–2·5) (André, ). The non‐inferiority of the results observed in the arm not receiving INRT was refuted due to the broad 95% CI.…”

FDG-PET–driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study

“…For each patient, PET0, PET2, and PET4 images were sent within 24 hours to 3 central panel PET experts (M.M., A.B.-R., or S.B.). PET2 and PET4 were binary interpreted as positive or negative, as per international harmonization project (IHP) criteria, 14 with the previously published precision 13,15,16 : the "clearly increased activity relative to the reference background," which defines positive residual uptake in the IHP criteria, should be at least 25% higher than this background. A central review was performed within 72 hours of receiving PET2 images, and the final result was sent back to the investigator to allow planning of stem cell harvest after cycle 3 in case of positive PET2.…”

18F-FDG PET/CT in Lymphoma: Has Imaging-Directed Personalized Medicine Become a Reality?

“…The 3-y progression-free survival (PFS) was 97.1% for patients receiving involved-field radiotherapy versus 90.8% for no further treatment in a perprotocol analysis (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.13 to 4.95; P 5 0.02). Similar results were reported in the H10 trial; patients who were in CMR after 2 cycles of ABVD were randomized using a PET-driven schema to either standard therapy (3-4 cycles of ABVD followed by involved-node radiotherapy, for favorable and unfavorable disease, respectively) or 4-6 cycles of ABVD alone (for favorable and unfavorable disease, respectively) (6 [unfavorable]; P 5 0.03). Combined-modality therapy thus resulted in a small improvement in disease control in both trials, although the high PFS and lack of effect on overall survival (OS) suggest that many patients may be cured using chemotherapy alone.…”