Role for PET Imaging in Reducing Tx Toxicity in Advanced Hodgkin Lymphoma?

There is new hope of reduced treatment toxicity in the management of advanced Hodgkin lymphoma (HL). It may be possible to use positron emission tomography (PET) to inform treatment de-escalation in a significant number of patients.

French investigators reported at 23rd Congress of the European Hematology Association (EHA, abstract S110) that a strategy of de-escalated treatment may be possible in patients with advanced HL who reach a metabolic response after only 2 cycles of escalated BEACOPP (an intensified regimen consisting of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Results from their phase III trial showed that  patients who received a de-escalated regimen were able to gain disease control similar to that achieved with 6 cycles of escalated BEACOPP, but with lower toxicity rates.

Olivier Casasnovas, MD, from the department of hematology at the Hôpital François Mitterrand, Dijon, France, presented the final analysis of a randomized phase III study comparing an early PET-driven treatment de-escalation against a non–PET-monitored strategy in patients with advanced stages of HL. Dr. Casasnovas and colleagues noted that treatment with 6 cycles of BEACOPP is known to provide better long-term disease control than ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) in advanced HL. However, it is also associated with more frequent hematological toxicity and a higher risk of myelodysplasia/acute leukemia and infertility.

The AHL2011 randomized phase III study demonstrated that a de-escalation treatment with a switch from BEACOPP to ABVD is possible after 2 cycles of BEACOPP in most patients (84%) who reached a negative PET scan after 2 cycles of BEACOPP. The de-escalation regimen in these patients was associated with maintaining the same level of disease control but significantly reducing the risk of treatment toxicity compared with patients who received the standard 6 cycles of BEACOPP.

The findings from the study suggest that a de-escalation approach based on the early response assessment using functional imaging (PET) may improve management of advanced HL, by providing a better balance between the tolerability and efficacy of BEACOPP-based treatment. The study also demonstrated that this approach led to excellent patient outcomes, with a 5-year progression free survival (PFS) rate of greater than 85% and an overall survival (OS) rate of  over 95%.

The trial included 823 previously untreated patients with advanced classical HL; 413 were randomized to standard BEACOPP and 410 were randomized to the experimental arm. Dr. Casasnovas and colleagues found 84% of the patients in the experimental arm reached a negative PET after 2 cycles of treatment, and then received a de-escalated therapy. When the investigators compared the patient groups, they found that disease control was similar in both arms. The PFS rates were 85.7% in the BEACOPP arm and 86.2% in the de-escalated patients. The OS findings were also similar; 5-year OS was 96.4% for the BEACOPP arm and 95.2% in the de-escalated group.

The investigators concluded that PET scans performed after 2 cycles of BEACOPP can be safely used to guide subsequent treatment in patients with advanced HL. Adopting this approach, they said, may allow patients to switch to 4 cycles of ABVD without impairing disease control while receiving an added benefit of significantly reduced treatment-related toxicity.