Nilanjan Ghosh, MD, PhD
PET-adapted therapy has been incorporated for the last 5 to 7 years in Hodgkin lymphoma, says Nilanjan Ghosh, MD, PhD, a physician at Levine Cancer Institute.
A recent study published in the Journal of Clinical Oncology
) showed that the use of PET-adapted therapy was successfully implemented in determining whether patients with stage IIB to IVB Hodgkin lymphoma should go from receiving doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP).
After receiving 2 cycles of ABVD, patients received an interim PET scan. Those who presented with PET2 positivity were given BEACOPP. Patients with PET2-positivity saw a 3-year progression-free survival (PFS) rate of 60% (95% CI, 51%-68%) and a 3-year overall survival (OS) rate of 89% (95% CI, 82%-93%). In the PET2-negative patients, the 3-year PFS rate was 87% (95% CI, 84%-89%) and the 3-year OS rate was 99% (95% CI, 97%-99%). At least 2 other studies incorporating PET adaptive therapy, S0816 and RATHL, have shown similar outcomes.
About 20% of patients are PET positive after 2 cycles of ABVD in advanced Hodgkin lymphoma and, despite dose escalation to BEACOPP, their outcomes don’t appear to be as good as those who are interim PET negative. However, there are patients who relapse, despite a negative interim PET scan. Therefore, interim PET scan is not perfect in predicting outcome, Ghosh says.
As the use of PET-adapted therapy continues to be refined, so do immunotherapy efforts and clinical trial designs that will examine combinations of chemotherapy and PD-1 inhibitors.
In an interview during the 2018 OncLive®
State of the Science Summit™
on Hematologic Malignancies, Ghosh discussed the advances and ongoing research in frontline treatment of patients with Hodgkin lymphoma.
OncLive: Please provide an overview of your presentation.
: I spoke about the frontline treatment of early-stage and advanced-stage Hodgkin lymphoma. I presented some of the data about PET-adapted treatment in newly diagnosed Hodgkin lymphoma, as well as the introduction of brentuximab vedotin (Adcetris) with adriamycin, vinblastine, and dacarbazine (AVD). Brentuximab vedotin with AVD is a non-PET–adapted treatment and has been recently FDA approved in the frontline treatment of patients with stage III and IV Hodgkin lymphoma.
I discussed ways and means by which many investigators have worked on, either reducing bleomycin exposure or trying to get rid of bleomycin from the frontline [setting] of Hodgkin lymphoma. I also explored the role of radiation in frontline treatment, especially for patients who get a negative PET scan at the end of treatment.
Can you speak to the efficacy of PET-adapted therapy?
There have been multiple clinical trials that have utilized PET-adapted therapy. A little more than a decade ago, a paper was published by Gallamini et al in JCO
showing that patients who had a positive PET scan after 2 cycles of ABVD, known as the interim PET scan, had very poor outcomes compared with patients who had a negative PET. That almost trumped the standard prognostic factor, called the International Prognostic Score in Hodgkin Lymphoma.
Many clinical trials were designed to look at ways to improve the outcomes of PET-positive patients after the interim PET scan. In most studies, interim PET-positive patients were dose escalated up to BEACOPP. There was 1 trial where [investigators] dose-escalated patients to a regimen called ifosfamide, gemcitabine, and vinorelbine (IGEV) followed by autologous transplant to try to improve outcomes in this group. Those trials showed that the interim PET-positive patients achieved a PFS in the 60% to 75% range after dose escalation, whereas the PET-negative patients were in the 80% to 85% range. The results showed a significant improvement from not doing PET-adapted [therapy]. As a proportion, there are more patients who relapse in the PET-positive group, but there is still a significant number of patients who relapse after obtaining interim negative PET scan.
How has the approval of brentuximab vedotin impacted sequencing strategies?
We haven't seen sequencing strategies because there has not been long-term follow-up after brentuximab plus AVD.