A response-adapted, PET-guided first-line strategy that used nivolumab (Opdivo) plus chemotherapy produced promising response rates and allowed for the omission of radiotherapy in patients with advanced-stage classical Hodgkin lymphoma, according to data from the phase 2 FINISH-HL trial (NCT07209059), which were presented at the
Patients in the trial had previously untreated advanced-stage classical Hodgkin lymphoma and received PET assessment after 2 cycles of nivolumab plus chemotherapy. Those with complete metabolic responses (CMRs) underwent chemotherapy de-escalation, and those with partial metabolic responses (PMRs) continued treatment for up to 6 cycles.
Among patients who underwent PET assessment (n = 43), 83% achieved CMR, and 17% achieved PMR. At a median follow-up of 9.1 months (range, 2.2-18.8) among evaluable patients in the trial (n = 35), this strategy led to an end-of-treatment CMR rate of 100%. Moreover, all of these patients omitted radiotherapy and did not experience relapse or progression of their disease.
“This PET-adapted nivolumab-based strategy demonstrated high early metabolic response rates and enabled chemotherapy de-escalation with radiotherapy omission in advanced-stage classical Hodgkin lymphoma,” Hunan Julhakyan, MD, PhD, and coauthors wrote in a poster of the data. “PET2 may remain clinically informative for treatment adaptation during nivolumab-containing therapy when preceded by intensive induction.”
Julhakyan is a senior researcher at the National Research Center for Hematology in Moscow, Russia.
The prospective, single-center study enrolled patients who were between 18 and 60 years with previously untreated classical Hodgkin lymphoma.2 Patients also needed to have at least 1 measurable lesion that was at least 15 mm in diameter, an ECOG performance status of 2 or less, and adequate organ function, including serum creatinine levels of 0.2 mmol/L or lower.
If patients had active hepatitis B or C infections, prior or active autoimmune disease that required systemic therapy, positive testing for HIV, or a history of non-infectious pneumonitis requiring corticosteroids, they were not enrolled in the trial.
All patients received induction with 40 mg of nivolumab every 2 weeks plus 2 cycles of etoposide at 100 mg/m² on days 1 to 3, 25 mg/m² of doxorubicin on day 1, 650 mg/m² of cyclophosphamide on day 1, 1.4 mg/m² of vincristine on day 8, 40 mg/m² of prednisolone on days 1 to 7, and 375 mg/m² of dacarbazine on day 1 (N40-EACOPD-14), for 14 day cycles followed by PET2 assessed per LYRIC criteria.1
Patients who achieved a CMR folllowing PET assessment de-escalated to 2 cycles of nivolumab plus doxorubicin, vinblastine, and dacarbazine followed by 2 cycles of single-agent nivolumab. Patients with a PMR continued N40-EACOPD-14 for up to 6 total cycles.
At baseline (n = 43), the median patient age was 29 years (range, 18-43), 56% of patients had bulky mediastinal disease, 49% of patients had stage III or IV disease, 30% of patients had extranodal involvement, 51% of patients had B symptoms, and 14% of patients had an International Prognostic Score of 3 or higher. Three patients had a pre-existing autoimmune disease, 2 of whom had autoimmune thyroiditis, and 1 of whom had multiple sclerosis.
The investigators noted that treatment was generally well tolerated. Grade 3 to 4 neutropenia occurred in 17% of patients, and febrile neutropenia occurred in 10% of patients; grade 3 infections were not observed. Grade 3 immune-related adverse effects (AEs) occurred in 8% of patients, consisting of thyroiditis in 2 patients and periarthritis in 1; these AEs were described as manageable and resolved without nivolumab discontinuation. Among the 3 patients with a pre-existing autoimmune disease at baseline, no reactivation was observed during treatment.
