Positron Emission Tomography–Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study

Abstract

PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.

Hodgkin lymphoma: 2023 update on diagnosis, risk‐stratification, and management

“…However, as outlined below, the FDG-PET results during or after frontline treatment may have greater prognostic significance than the abovementioned pretreatment risk stratification. [28][29][30]…”

“…[31][32][33] A positive interim FDG-PET scan after 2 cycles of treatment may result in intensification of therapy and a positive PET scan at the end of treatment may result in the addition of consolidation radiotherapy to the positive sites. 30,32,33 A positive PET scan at any point may also result in a repeat biopsy to confirm or exclude persistent disease. 34 The use of PET scans in this fashion is based on studies showing that patients with a positive FDG-PET scan at the completion of treatment have a significantly higher recurrence rate regardless of the findings of the CT scan.…”

“…The AHL2011 and RATHL studies are illustrative of this approach. 30,33 In the AHL2011 study, patients were prospectively randomized between 6 cycles of BEACOPP and a PETdriven arm after 2 cycles of BEACOPP, delivering 4 cycles of ABVD in PET2 negative patients and 4 cycles of BEACOPP in PET2 positive patients. In long-term follow-up, the PFS and OS were similar in both arms.…”

“…To improve clinical outcomes, studies have utilized FDG‐PET scans to identify patients who may benefit from intensification or de‐escalation of therapy. The AHL2011 and RATHL studies are illustrative of this approach 30,33 . In the AHL2011 study, patients were prospectively randomized between 6 cycles of BEACOPP and a PET‐driven arm after 2 cycles of BEACOPP, delivering 4 cycles of ABVD in PET2 negative patients and 4 cycles of BEACOPP in PET2 positive patients.…”

“…A negative interim FDG‐PET may allow for de‐escalation of therapy by abbreviating the number of cycles given, omitting radiation therapy, or excluding bleomycin from the treatment to avoid pulmonary toxicity 31–33 . A positive interim FDG‐PET scan after 2 cycles of treatment may result in intensification of therapy and a positive PET scan at the end of treatment may result in the addition of consolidation radiotherapy to the positive sites 30,32,33 . A positive PET scan at any point may also result in a repeat biopsy to confirm or exclude persistent disease 34 .…”