Adding Adcetris (brentuximab vedotin) to frontline chemotherapy for patients with Hodgkin lymphoma led to improved outcomes, regardless of post-therapy PET scan results, which are typically used to predict outcomes, according to research presented at the 2023 School of Hematologic Oncology (SOHO) Annual Meeting.
Findings from the review showed that among the 40 patients treated with Adcetris plus doxorubicin, vinblastine and dacarbazine — a combination known as BvAVD — 24 were PET2 negative, meaning that the second PET scan detected cancer, and 12 were PET2 positive. All the patients who were PET2 negative had a negative end-of-treatment-PET, which indicated no progression of cancer. Of the 12 PET-positive patients, four had a positive end-of-treatment PET.
No meaningful impact on the management of patients was noted with the results of PET2 scans, and only one patient had a change in chemotherapy regimen after PET2 among all 40 patients who started on the BvAVD regimen initially. Additionally, no differences were observed in outcomes between the patients who were PET2 positive with a negative end-of-treatment-PET vs PET2-negative patients.
“We concluded that incorporation of (Adcetris) into frontline treatment results in superior efficacy, regardless of PET2 results. Our data, along with previous studies, points to the loss of predictive value, and therefore, redundancy of an interim PET2 scan, providing the evidence for safe omission of PET2 in treatment regimens containing (Adcetris),” Dr. Ravand Samaeekia, chief resident at Loma Linda University Internal Medicine, said during the presentation.
The standard-of-care for patients with Hodgkin lymphoma is interim PET2 due to its prognostic value and utility in PET-adapted treatment protocols. However, with the incorporation of Adcetris, a novel, anti-CD30 antibody-drug conjugate, into frontline treatment, the value of PET2 imaging is uncertain.
Investigators sought to determine whether interim PET assessment after two cycles of treatment still has predictive value for patients with Hodgkin lymphoma by reviewing frontline trials incorporating Adcetris and reported interim PET data. These trials were evaluated for three years, between December 2018-December 2022, and patients were from Loma Linda University Cancer Center. PET2 and end-of-treatment PET results of patients with Hodgkin lymphoma treated with BvAVD in the same period were also reviewed.
In three studies which have already been performed, ECHELON-1, AHOD1331 and BREACH, Adcetris was incorporated into the frontline and interim PET data were assessed. Each of these studies showed that progression-free survival or overall survival rates were significantly higher with Adcetris among patients with PET2-negative or PET2-positive disease.
In the ACCRU-LY study, which examined Adcetris with Opdivo (nivolumab) as a frontline treatment for patients with Hodgkin lymphoma, preliminary data showed a 97% rate of interim PET negativity with a 100% PFS rate at two years. The combination, which eliminated chemotherapy, was also well tolerated; however, some neuropathy concerns were noted.Although this trial did not meet its prespecified activity criteria, as the overall response rate noted was 61% instead of 80%, the combination was active in older patients.
“All these clinical trials are supporting the idea that receiving Adcetris has benefits, regardless of being a PET-positive or PET-negative patient,” said Samaeekia.
In the review presented at SOHO 2023, 40 patients were included and treated with BvAVD. A total of 24 were PET2-negative, and 12 were PET2-positive. Nineteen (48%) patients were male, and the median age was 22 years (range, 11-83). At initial diagnosis, 11 patients (28%) had Ann Arbor Stage 2 disease, 15 (37%) had stage 3 and 14 (35%) had stage 4 disease. Nineteen percent of patients had a low (0-2) International Prognostic Score while 21% had a high score (3-7), and the majority of patients (68%) had an ECOG performance status of 0-1, meaning that they could independently perform all or most of their daily activities.
All 24 patients with PET2-negative disease and eight patients with PET2-positive disease with a negative end-of-treatment PET remained in complete remission at the end of treatment.
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