PET-Adapted Therapy in Classical Hodgkin Lymphoma Allows Omission of Radiation Therapy

Patients with early-stage classical Hodgkin lymphoma (cHL) and bulky disease who achieved a response after two cycles of chemotherapy were able to avoid radiation therapy, while escalated therapy led to noninferior outcomes in those who did not have an initial response, according to results from the Alliance for Clinical Trials in Oncology’s CALGB-50801 trial. In the trial, which evaluated a positron emission tomography (PET)─adapted approach to cHL therapy also led to “excellent” progression-free survival (PFS) outcomes in all patients, study authors noted.

Lead author Ann S. LaCasce, MD, from Dana-Farber Cancer Institute in Boston, Massachusetts, presented these results at the 2021 American Society of Clinical Oncology Annual Meeting.

CALGB-50801 enrolled patients ages 18 to 60 who had stage IA-IIB cHL with bulky disease >10 cm (or >0.33 max intrathoracic diameter on chest X-ray). Patients received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), then underwent PET that was centrally reviewed. Those who achieved PET negativity (defined as a Deauville score of 1-3), received four additional cycles of ABVD; those who had PET-positive scans received four cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) plus 30 Gy involved-site radiation therapy.

A total of 101 patients were enrolled between May 2010 and October 2017. After excluding patients who were found to have non-bulky or stage III disease or who had missing PET scans, 94 patients were evaluable for this analysis.

After two cycles of chemotherapy, 73 patients (78%) were considered PET-negative and 21 were considered PET-positive. Most of the patients who were PET-positive had stage IIB disease (61.9%).

Dr. LaCasce reported that therapy was “generally well tolerated.” The most common adverse event was neutropenia (93% in PET-negative patients and 100% in PET-positive patients). Grade >3 febrile neutropenia was observed in 8% of PET-negative and 10% of PET-positive patients. In the PET-negative and PET-positive groups, approximately 70% and 76% of patients received all six cycles of bleomycin, respectively. The most common pulmonary toxicity observed was any-grade cough (62% in each group).

With a median follow-up of 5.5 years, the estimated rates of three-year PFS were 93% in PET-negative patients and 90% in PET-positive patients, or 92.3% across the entire patient population. The study met its primary endpoint, as the PFS hazard ratio for PET-positivity versus PET-negativity was 1.03, less than the protocol-defined hazard ratio of 4.1, the researchers reported.

Rates of three-year overall survival were also similar (99% in PET-negative patients and 94% in PET-positive patients). Dr. LaCasce reported one death in the PET-positive group (related to pneumonia and lymphoma) and three deaths in the PET-negative group (related to lymphoma, anaplastic astrocytoma, and chronic obstructive pulmonary disease).

“Excellent PFS outcomes were observed in all patients using a PET-adapted approach that allowed omission of radiation therapy in 78% of patients,” Dr. LaCasce and coauthors concluded, who added that those with PET-positive disease did not have inferior outcomes after therapy escalation. “Unexpectedly, PET-positive patients with bulky disease appeared to have improved outcomes compared to patients with stage I/II non-bulky disease,” she added. However, this finding was limited by small patient numbers and needs to be further explored.

Study authors report no relevant conflicts of interest.

Reference

LaCasce AS, Dockter T, Ruppert AS, et al. CALGB 50801 (Alliance): PET adapted therapy in bulky stage I/II classic Hodgkin lymphoma (cHL). Abstract #7507. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.