PET-Guided De-escalation a Safe, Effective Approach in Advanced Hodgkin Lymphoma

Olivier Casasnovas, MD

Olivier Casasnovas, MD

In patients with untreated advanced-stage classical Hodgkin lymphoma, PET can be safely used to guide treatment after 2 cycles of upfront de-escalated BEACOPP (BEAesc), according to the final analysis of the phase III LYSA study presented at the 2018 European Hematology Association Congress.^1,2

In the randomized study, presented by lead author Olivier Casasnovas, MD, 823 patients were enrolled; there were 413 patients in the standard arm and 410 patients in the experimental arm, which was driven by PET. In the experimental arm, PET2-negative patients received 4 cycles of ABVD after 2 BEAesc cycles, and PET2-positive patients received 4 cycles of BEAesc after the initial 2 cycles of BEAesc. The standard arm comprised of 6 cycles of BEAesc with no PET-driven strategy.

Investigators aimed to evaluate whether de-escalation of BEACOPP in patients with advanced Hodgkin lymphoma would be beneficial without diminishing disease control. PET positivity in the standard arm and the experimental arm were comparable (12% vs 13%).

“The purpose of this study was to evaluate the strategy of escalated treatment in patients with advanced Hodgkin lymphoma, said Casasnovas, of Clinique Centre Hospitalier Universitaire de Dijon in Dijon, France. “[Patients received] 2 cycles of BEAesc in order to obtain disease control similar to 6 cycles of BEAesc with lower toxicity.”

The 5-year progression-free survival (PFS) was 85.7% in the experimental arm, which was comparable with the 5-year PFS in the standard arm (86.2%). Additionally, the 5-year overall survival (OS) in the experimental arm slightly edged out the 5-year OS in the standard arm (96.4% vs 95.2%), according to Casasnovas.

Historically, BEAesc has been shown to improve PFS, but it has not demonstrated an improvement in OS versus ABVD in patients with advanced Hodgkin lymphoma.

“The disease control was similar in both arms, and PFS was quite satisfactory with a 5-year PFS of 85.7% in the experimental arm. The overall survival was also similar in both arms,” said Casasnovas.

The estimated 4-year PFS at a median follow-up of 50 months in the PET-driven experimental arm was comparable to the standard arm (87.1% vs 87.4%). In the overall population, PET2-positive patients had a significantly lower 4-year PFS compared with patients who were PET2-negative (70.7% vs 90.4%;P<.0001). This was also true in both randomized arms (75.1% vs 94% and 70.8% vs 91.6% in the standard and PET-driven arms, respectively;P<.0001 for both). The OS was similar in both arms.

The PET scan was analyzed centrally in real-time, which Casanovas said makes this approach quite easy to implement in practice. Based on these results, 346 (84%) patients in the experimental arm received 4 cycles of ABVD and 51 (12%) received 4 additional cycles of BEAesc.

"PET performed after 2 cycles of BEAesc can be safely used to guide subsequent treatment and supports the response-adapted strategy [of] delivering 4 cycles of ABVD for patients with negative PET2,&rdquo; said Casasnovas.

Findings showed that treatment can be reduced in 84% of patients without impairing the disease control, allowing a significant reduction in treatment-related toxicity in most patients.

Toxicity was higher in patients who received 6 cycles of BEAesc compared with patients who received 2 cycles of BEAesc plus 4 cycles of ABVD. Serious adverse events (AEs) were reported in both arms, although the rates of these AEs were notably lower in the experimental arm.

&ldquo;The toxicity in the experimental arm, including serious AEs was significantly reduced,&rdquo; said Casasnovas. &ldquo;We reduced the risk over serious AEs about 40%.&rdquo;

The most frequent grade &ge;3 AEs were anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%) in the standard arm and experimental arm, respectively. Of the 823 patients enrolled, 204 serious treatment-related AEs were reported in 119 (26%) of patients in the standard arm, and 102 serious treatment-related AEs were reported in 62 (17%) patients in the experimental arm. Subsequently, there were 6 deaths in the standard arm and 2 in the experimental arm

"This approach allows us to provide similar patient outcomes compared with standard BEACOPP treatment," said Casasnovas. "It is probably the new standard of treatment in this disease."

These are encouraging data for patients with PET2-negative advanced-stage Hodgkin lymphoma, noted investigators. Conversely, the findings showed a higher risk of disease progression for patients who were PET-positive after 2 cycles of BEAesc. Investigators have suggested that these results should encourage the field to develop new treatment options for patients with advanced-stage classical Hodgkin lymphoma who are PET2-positive.

References:

1. Casasnovas O, Brice P, Bouabdallah R, et al. Final analysis of the AHL2011 randomized phase III LYSA study comparing an early PET driven treatment de-escalation to a not PET-monitored strategy in patients with advanced stages Hodgkin lymphoma. In: Proceedings from the 2018 European Hematology Association Congress; June 14-17, 2018; Stockholm, Sweden. Abstract S110.
2. Casasnovas, O. Outstanding disease control with a minimized BEACOPP exposure and toxicity in patients with advanced Hodgkin lymphoma. In: Proceedings from the 2018 European Hematology Association Congress; June 14-17, 2018; Stockholm, Sweden. Session AHL2011.