Safely Skip PET2 After Brentuximab in Hodgkin Lymphoma?

Neil Osterweil

September 13, 2023

HOUSTON — It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda University Medical Center in California.

These studies, including one conducted by Samaeekia's team, provide "evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin," Samaeekia, who presented the data at SOHO on September 8, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, "there are obviously challenges associated with implementing a PET-guided approach," said Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients' risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Samaeekia's team analyzed findings from three trials — ECHELON-1, AHOD1331, and BREACH — which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2-negative (94.9% vs 90.6%; hazard ratio [HR], for death, 0.54) as well as those who were PET2-positive (95% vs 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab — 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab "eliminated the predictive value of the interim PET assessment." The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Samaeekia and colleagues found that 24 were PET2-negative and 12 were PET2-positive. All patients who were PET2-negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET-positive at the end of treatment. Only one patient overall changed regimens following PET2.

Samaeekia's team concluded that PET2 scan results "did not have any meaningful impact" on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Hutchings, from the Rigshospitalet in Copenhagen, Denmark, pointed out that four of the 12 PET2-positive patients treated at Loma Linda were still PET-positive at the end of treatment.

Even so, Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make "us feel better," but it ultimately doesn't "make any difference in our management."

In the AHOD1331 study, "the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative," added session co-moderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester Medical Center in New York.

The study by Samaeekia and colleagues was internally funded. Samaeekia reports no relevant financial relationships. Hutchings has previously reported consultancy and research funding from numerous companies. Friedberg reports no relevant financial relationships.

Society of Hematologic Oncology 2023. Abstract HL-642. Presented Sept. 8, 2023.

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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