MADRID—Patients with advanced Hodgkin lymphoma (HL) who are PET-negative after initial treatment with 2 cycles of eBEACOPP* should only receive 2 additional cycles of the therapy, new research suggests.
In the HD18 trial, PET-2-negative patients who received 4 cycles of eBEACOPP had non-inferior progression-free survival (PFS) and significantly better overall survival (OS) than PET-2-negative patients who received 6 or 8 cycles of the treatment.
Patients who received 4 cycles also had less severe toxicity and fewer second neoplasms than patients who received more cycles of eBEACOPP.
“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far,” said Peter Borchmann, MD, of University Hospital of Cologne in Germany.
“That’s why we recommend treatment with PET-2-guided eBEACOPP for patients with newly diagnosed, advanced-stage Hodgkin lymphoma.”
Dr Borchmann presented results from HD18 at the 22nd Congress of the European Hematology Association (EHA) as abstract S150.
Patients and treatment
Dr Borchmann and his colleagues set out to determine if they could decrease the number of eBEACOPP cycles in patients with negative PET-2 without compromising treatment efficacy.
From May 2008 to July 2014, the researchers recruited 2101 patients with newly diagnosed, advanced-stage HL.
Patients who were PET-negative after 2 cycles of eBEACOPP (n=1005) were initially randomized to receive 6 additional cycles of eBEACOPP or 2 additional cycles—a total of 8 cycles or 4 cycles, respectively. The protocol was later amended (in June 2011), and the total number of cycles in the standard therapy arm was reduced to 6.
There were 504 patients in the standard therapy arm—288 who received 8 cycles of eBEACOPP and 216 who received 6 cycles. There were 501 patients who received 4 cycles of eBEACOPP.
Sixteen patients in the standard therapy arm and 17 in the 4-cycle arm also received radiotherapy.
The median age was 32 (range, 18-60) in the standard therapy arm and 33 (range, 18-60) in the 4-cycle arm. Sixty-three percent and 62% of patients, respectively, were male.
Eight percent of patients in both arms had Ann Arbor stage IIB disease. Fifty-seven percent in the standard therapy arm and 55% in the 4-cycle arm had stage IIIA/B. And 35% and 36%, respectively, had stage IVA/B disease.
Thirty-five percent of patients in both arms had an IPS stage of 0-1. Fifty-one percent in the standard therapy arm and 52% in the 4-cycle arm had an IPS stage of 2-3. And 14% in both arms had an IPS stage of 4-7.
The median duration of therapy was 173 days (range, 41-266) for patients randomized to receive 8 cycles of eBEACOPP, 129 days (range, 35-178) in patients randomized to receive 6 cycles, and 85 days (range, 42-133) in patients randomized to receive 4 cycles.
One patient in the 6-cycle group received more than 6 cycles, and 6 patients in the 4-cycle arm received more than 4 cycles.
PFS and OS
The median follow-up was 55 months. The estimated 3-year PFS was 92.3% in the standard therapy arm and 94.8% in the 4-cycle arm. The estimated 5-year PFS was 91.2% and 91.8%, respectively. The hazard ratio was 0.88.
“[Based on these data,] we can conclude that 4 cycles are as effective as 6 or 8 cycles,” Dr Borchmann said.
The estimated 3-year OS was 95.9% in the standard therapy arm and 98.7% in the 4-cycle arm. The estimated 5-year OS was 95.4% and 97.6%, respectively. The hazard ratio was 0.36 (P=0.006).
Toxicity and second neoplasms
Grade 3/4 organ toxicity occurred in 22% of patients in the 8-cycle group, 13% in the 6-cycle group, and 8% in the 4-cycle group. Grade 4 anemia, thrombocytopenia, or infection occurred in 59%, 53%, and 38%, respectively.
Treatment-related morbidity occurred in 66% of patients in the 8-cycle group, 61% in the 6-cycle group, and 41% in the 4-cycle group.
Eighteen patients in the standard therapy arm had second neoplasms—8 with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), 5 with non-Hodgkin lymphoma (NHL), and 5 with solid tumors.
Thirteen patients in the 4-cycle arm had second neoplasms—2 with AML/MDS, 8 with NHL, and 3 with solid tumors.
Causes of death
The cause of death was HL for 0.6% of patients (n=3) in the standard therapy arm and for 0.8% of patients (n=4) in the 4-cycle arm.
The cause of death was second malignancy for 2.2% of patients (n=11) in the standard therapy arm. Five patients died of AML, 3 of NHL, and 3 of solid tumor malignancies.
One patient (0.2%) in the 4-cycle arm died as a result of a second malignancy, which was AML.
Toxicity related to study treatment was the cause of death for 1.2% (n=6) of patients in the standard therapy arm. Five of the patients died of infection, and the sixth died of ischemic stroke.
None of the patients in the 4-cycle arm died of toxicity related to study treatment.
Other causes of death included toxicity of salvage treatment (0.4%, n=2 in both arms), other disease (0.2%, n=1 in both arms), accident (1 patient [0.2%] in the 4-cycle arm), and unknown cause (2 patients [0.4%] in the standard arm).
“[With 4 cycles of therapy,] we had a significant and very relevant reduction of severe, acute hematological and non-hematological toxicities, and this was accompanied by a relevant reduction of mortality for other reasons than HL,” Dr Borchmann said. “And we’ve almost eliminated HL as a cause of death in this trial.”
*dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone