Study Questions Value of Interim PET Imaging to Guide Frontline Hodgkin Treatment

HOUSTON -- Interim PET-CT imaging (PET2) had almost no impact on clinical decision-making for Hodgkin lymphoma treated with brentuximab vedotin (Adcetris), according to a small clinical study reported here.

One of 40 patients had a change in treatment based on PET2 results, regardless of whether the scans were positive or negative. Outcomes did not differ between patients with positive scans at interim imaging and negative end-of-treatment scans as compared with patients who had negative interim scans.

The findings add to those of recent studies that have shown limited value for interim PET imaging in patients treated with brentuximab, said Ravanda Samaeekia, MD, of Loma Linda University Cancer Center in California, at the Society of Hematologic Oncology (SOHO) meeting.

"We concluded that incorporation of brentuximab vedotin into frontline treatment results in superior efficacy regardless of PET2 results," he said. "Our data, along with previous studies, point to the loss of predictive value and therefore redundancy of an interim PET scan, providing evidence for safe omission of PET2 in treatment regimens containing brentuximab."

During a discussion that followed the presentation, an unidentified member of the audience pointed out that some investigators in the ECHELON-1 study that established the role of brentuximab in Hodgkin lymphoma have made similar statements regarding omission of interim PET imaging.

"I fault that statement a little bit," said the speaker. "In order to say that [about omitting PET2], you must mean that a 2-year progression-free survival of 64% [among PET-positive patients in ECHELON-1] is satisfactory in Hodgkin lymphoma. Do you mean that?"

The speaker went on to point out that four patients in the Loma Linda series had positive PET2 scans and remained positive at end of treatment.

"I hear what you're saying, but even with those patients we didn't make any changes in the regimen," Samaeekia replied. "[The treating oncologists] all sort of agreed we take a PET2 scan but since it's not going to make in difference in our management, it just makes us feel better."

Another unidentified speaker said ECHELON-1 had an older patient population and that the Loma Linda patients were more in line with pediatric population of the AHOD1331 study. Findings on PET2 also had little impact on outcomes, whether the scans were positive or negative.

To close out the discussion, SOHO session moderator Catherine Diefenbach, MD, of NY Langone Perlmutter Cancer Center in New York City, noted "that the question still remains, so what do you do with patients who are still PET positive at the end of treatment?"

Samaeekia demurred, saying that he was not involved in treatment decisions for the patients.

Interim PET-CT after two cycles of chemotherapy has been standard of care for Hodgkin lymphoma because of its prognostic value and utility in PET-adapted treatment protocols. PET-guided approaches to treatment are costly and time-consuming, and variability in scan interpretation may affect decisions, said Samaeekia. Additionally, PET2-based intensification of treatment can increase toxicity.

The value of PET2 since the incorporation of brentuximab into frontline treatment is unclear, he continued. To address the issue, investigators reviewed recent trials of frontline therapy for Hodgkin lymphoma. They also retrospectively reviewed end-of-treatment PET results for patients treated with brentuximab-containing regimens at Loma Linda.

In addition to the ECHELON-1 and AHOD1331 studies, the review included the BREACH and the ACCRU-LY1601 trials in adults with Hodgkin lymphoma. All four trials compared brentuximab-containing regimens versus chemotherapy, and all four showed that brentuximab-treated patients had better outcomes, regardless of whether PET2 scans were positive or negative.

The retrospective review of the Loma Linda cases involved 40 patients who received frontline brentuximab plus chemotherapy. The study population include 19 men, and the median age was 22. Samaeekia said 17 patients were ages 21 or younger and 18 were ages 22-45. Stage distribution consisted of 11 patients with stage II disease, 15 with stage III, and 14 with stage IV.

Of 36 patients with complete information, 24 had negative PET2 scans and 12 had positive PET2 scans. All of the patients with PET2-negative scans were also PET-negative at end of treatment, whereas four of 12 with PET2-positive results remained PET2 positive at the end of treatment.

"The results of the PET2 scan did not have any meaningful impact on management of the patients," said Samaeekia. "All 40 patient [continued brentuximab] regardless of their PET2 results. The one patient who switched continued brentuximab and nivolumab [Opdivo] was added."

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