PET Can Identify Low-Risk Patients With Hodgkin's Lymphoma Who Need No Further Treatment Following Three Cycles of ABVD
Patients with early stage Hodgkin's lymphoma who have a negative positron emission tomography (PET) scan after 3 cycles of ABVD (doxorubicin, bleomycin sulfate, vinblastine, and dacarbazine) can forego further treatment without compromising survival, said John Radford, MD. At the 54th Annual Meeting of the American Society of Hematology, he reported the results of the United Kingdom RAPID trial, in which PET-directed therapy provided an opportunity to avoid involved field radiotherapy (IFRT), the current standard of care following abbreviated chemotherapy in early stage Hodgkin's lymphoma.
According to Dr Radford, “A response-adapted approach based on centrally reviewed PET imaging reduces treatment time and costs, improves tolerability, and most importantly removes the burden of early and late toxicity of radiotherapy from the PET-negative population.”
The study included 602 patients with newly diagnosed stage IA or IIA Hodgkin's lymphoma who underwent PET imaging after 3 courses of ABVD. The PET scan was performed at 1 of 15 quality controlled PET Scan Centers across the United Kingdom. Patients with a positive PET scan received an additional course of ABVD followed by IFRT. Patients with a negative PET scan were randomized to 1 of 2 treatment arms. In arm 1, within 6 weeks after completion of course 3 of chemotherapy, patients underwent IFRT to disease areas. In arm 2, patients received no further treatment.
A positive PET scan was defined as a score of 3, 4, or 5, as assigned at core laboratory review—a PET scan was considered negative if it had a score of 1 or 2. The trial was powered to show non-inferiority of arm 2 compared with arm 1, defined as a 7% or less difference in progression-free survival (PFS) from 95% in arm 2.
Four hundred twenty-six (74.7%) PET scans were classified as negative, and 420 patients were randomized to arm 1 or arm 2 (6 PET-negative patients were not randomized). Twenty-five of 209 patients randomized to receive IFRT did not receive it—19 patients declined after they became aware of the randomization decision, 5 patients died, and 1 patient developed pneumonia.
At a median follow-up time of 48.6 months, PFS was 94.5% in arm 1 and 90.8% in arm 2 on an intention-to-treat analysis, a hazard ratio of 1.51 in favor of IFRT, which met the criterion for non-inferiority for no further treatment, said Dr Radford, University of Manchester, Christie National Health Service Foundation Trust, Manchester, UK. Overall survival was greater in those patients with no further treatment compared with IFRT (99.5% vs 97.1%).
In a per-protocol analysis of those patients who received their allocated treatment, which included 2 patients in arm 2 who received radiotherapy, 3-year PFS was 97% in arm 1 versus 90.7% in arm 2, which again met the criterion for non-inferiority of no further treatment.
“Using PET, it is possible to identify a population of patients with stage IA and IIA Hodgkin's lymphoma who have an excellent prognosis after 3 cycles of ABVD,” said Dr Radford.