A PET-guided de-escalation treatment strategy is noninferior to standard care in patients with advanced Hodgkin lymphoma, according to phase 3 results published in the Journal of Clinical Oncology.1

Researchers observed no difference in efficacy outcomes with PET-guided de-escalation of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) compared with the standard 6 cycles of BEACOPP. In addition, the PET-guided strategy reduced toxicity.

The phase 3 AHL2011 trial (ClinicalTrials.gov Identifier: NCT01358747) was designed to investigate whether PET monitoring could allow for de-escalation by switching BEACOPP to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in early responders without loss of disease control.


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The trial enrolled 823 patients — 413 randomly assigned to standard treatment and 410 to the PET-driven strategy. Baseline characteristics were similar between the arms. The median age was 31 years in the standard arm and 29 years in the PET-driven arm (overall range, 16-60 years).

All patients received 2 cycles of BEACOPP induction. In the standard arm, patients completed 4 additional cycles of BEACOPP, regardless of their PET findings. In the PET-driven arm, patients who had positive PET2 results received 4 additional cycles of escalated BEACOPP, and those with negative PET2 results were switched to ABVD.  

Results

In the previously published primary analysis, progression-free survival (PFS) was similar between the standard and PET-driven arms, but early toxicity was reduced in the PET-driven arm.2

In the current analysis, the median follow-up was 67.2 months. Both PFS and overall survival (OS) were similar with the PET-driven approach and standard care, and late toxicity was reduced in the PET-driven arm.

The 5-year PFS rate in the intent-to-treat population was 87.5% in the standard arm and 86.7% in the PET-driven arm (hazard ratio [HR], 1.07; 95% CI, 0.74-1.57; P =.67). The 5-year OS rate was 97.7% in both arms (HR, 1.012; 95% CI, 0.50-2.10; P =.53).

Since the primary analysis, 1 patient in the standard arm developed grade 2 peripheral neuropathy. No adverse events of grade 3 or higher were reported during extended follow-up.

At last follow-up, 22 patients (2.7%) had developed a second primary malignancy — 13 (3.2%) in the standard arm and 9 (2.2%) in the PET-driven arm.

There were 109 pregnancies in the overall cohort — 44 in the standard arm and 65 in the PET-driven arm. Assisted reproductive technology was required more often in the standard arm than the PET-driven arm — 20.5% and 10.8%, respectively.

“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,” the researchers wrote.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Casasnovas RO, Bouabdallah R, Brice P, et al.Positron emission tomography-driven strategy in advanced Hodgkin lymphoma: Prolonged follow-up of the AHL2011 phase III Lymphoma Study Association study. J Clin Oncol. Published online January 6, 2022. doi:10.1200/JCO.21.01777
  2. Casasnovas R-O, Bouabdallah R, Brice P, et al. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): A randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2019;20(2):202-215. doi:10.1016/S1470-2045(18)30784-8