Bleomycin can be safely omitted after negative PET2 in HL
Photo by Jens Maus
LUGANO—Results of the RATHL trial indicate that bleomycin can be omitted from ABVD therapy following a negative interim FDG-PET scan in patients with Hodgkin lymphoma.
Progression-free survival (PFS) and overall survival (OS) were the same at 3 years for patients who were PET-negative after 2 cycles of ABVD and then continued therapy with or without bleomycin.
These results were presented at the 13th International Conference on Malignant Lymphoma (13-ICML).
Investigators based the RATHL study on the principles that it’s desirable to de-escalate treatment in the best responders to avoid late toxicity and that PET scans after 2 cycles of ABVD are highly predictive.
The team enrolled 1214 patients from 6 countries, 861 of whom were in the UK. Patients received a PET scan at staging, 2 cycles of ABVD, and then a second PET scan (PET2).
If patients were negative after PET2, they were randomized to receive 4 more cycles of ABVD or AVD and no radiotherapy.
If they were positive after PET2, patients received 4 cycles of BEACOPP-14 or 3 cycles of escalated BEACOPP. These patients then received a third PET scan, and the positive patients went on to receive radiotherapy or a salvage regimen.
The PET3-negative patients received 2 more cycles of BEACOPP-14 or one of escalated BEACOPP without radiotherapy.
Peter W. Johnson, MD, of the University of Southampton in the UK, presented the results of these treatment regimens during the plenary session of 13-ICML as abstract 008.
Patient characteristics
Patients were a median age of 33 (range, 18-79), and 55% were male. They had disease stages of II (41%), III (31%), or IV (28%).
Seventy-four percent of patients had a performance status of 0. Almost half (49%) had an IPS score of 2 to 3, and 18% had an IPS score of 4 or more. Thirty-two percent had bulky disease.
Investigators followed the patients for a median of 34.7 months (range, 1 day to 68.2 months).
Results after PET2
Seventy-seven patients were missing a second PET scan, mostly due to PET protocol violations of having to use the same scanner for the baseline and second scan and the same acquisition time.
“We were very strict on our quality control,” Dr Johnson said, “because we wished to make sure this was reproducible data.”
So the results after 2 cycles of ABVD treatment were based on 1137 patients.
PET-negative patients
More than 80% of patients were PET-negative after 2 cycles. Four hundred and sixty-nine patients were randomized to receive ABVD and 466 to AVD.
The groups were well-balanced in terms of median age, performance status, stage, B symptoms, bulky disease, and IPS score.
There was a significant excess of neutropenic fever (P=0.032) and infection (P=0.040) in those patients continuing on ABVD compared to AVD. And any hematologic toxicity was highly significantly different between the 2 arms (P<0.001).
“So we have demonstrated that continuing with bleomycin beyond cycle 2 is accompanied by significantly more toxicity,” Dr Johnson said.
Ninety-eight percent of patients in both cohorts received at least 6 cycles of therapy post-randomization.
At a median follow-up of 36.3 months, 65% of patients in the ABVD arm and 69% in the AVD arm achieved a complete remission (CR) or unconfirmed CR (CRu).
Fourteen patients died in each of the arms. Seven patients died of their disease in the AVD arm, compared with 1 in the ABVD arm. Slightly more patients died from toxicity in the ABVD arm.
The primary endpoint of PFS showed very little difference between the 2 arms. The 3-year PFS in the intent-to-treat analysis was 85.4% for patients in the ABVD arm and 84.4% for those in the AVD arm.
