Dose Escalation shows no benefit compared to continuing ABVD in Hodgkin's lymphoma patients with an interim PET deauville score of 4

Abstract

Abstract Introduction: Interim Fluorodeoxyglucose positron emission tomography (PET) conducted in patients with classic Hodgkin's Lymphoma (cHL) after two cycles of chemotherapy has emerged as a reliable predictor of progression-free survival (PFS) and overall survival (OS), surpassing traditional indicators such as disease stage and extranodal involvement. A negative interim PET (iPET) could facilitate treatment de-escalation, potentially involving reduced chemotherapy cycles, omitting radiotherapy, or excluding bleomycin to mitigate pulmonary toxicity. Conversely, a positive iPET may signal the need for treatment intensification, commonly achieved through escalated therapy with BEACOPP. However, in resource-limited regions, escalating to BEACOPP can be costly, challenging, and may not be readily available. Moreover, procarbazine is not avaliable in different regions in Latin America, including Brazil, and escalation should use Dacarbazine in this context. Methods: This retrospective cohort study analyzed patients diagnosed with cHL between January 2019 and January 2025 at a referral hospital in São Paulo, SP. Patients presenting with a Deauville score (DS) of 4 on iPET evaluation were selected for inclusion. Those lacking comprehensive treatment or PET result documentation were excluded. Data on clinical, laboratory, imaging, and histopathological parameters were extracted from electronic medical records. Patients were categorized into two groups based on post-iPET treatment: ABVD or escalated BEACOP-DAC. The primary endpoint was progression free survival and secondary endpoint was complete response (CR) rate after initial therapy. Results: Among 218 newly diagnosed patients with cHL, 31 (14%) were identified with a DS of 4 on iPET. The median age was 29 years (range, 20-74), with 58% female and 64.5% having advanced-stage disease. Initial treatment predominantly consisted of ABVD, except for one patient treated with AVD due to concerns on pulmonary toxicity of bleomycin. Post-iPET, 42% of patients had treatment escalated to BEACOP-DAC, while 58% continued with ABVD/AVD at the medical team's discretion. After a median follow-up of 39 months, PFS was not reached in the ABVD/AVD group versus 25 months in the BEACOPDAC, with no statistical difference (log-rank; p = 0.2). The 2-year PFS rate was 72% in the ABVD/AVD group (95% CI: 53.6–96.2%) and 54% in the BEACOPDAC group (95% CI: 32.6–89.1%). The secondary endpoint of CR after initial therapy was observed in 69.2% of the BEACOP-DAC group compared to 61.1% in the ABVD/AVD group (p = 0.932). Multivariate analysis, accounting for sex, age, disease stage, bulky mass, and B symptoms, indicated an odds ratio (OR) of 0.99 (95% CI = 0.18-5.32) for CR in the BEACOP-DAC arm. Notably, two patients in the BEACOP-DAC group required de-escalation to ABVD due to toxicity, while one patient in the ABVD group was moderately de-escalated to AVD. Conclusion: This real-world study demonstrates that escalating treatment to BEACOP-DAC for all patients with cHL and a DS of 4 did not provide significant benefit regarding treatment response, R/R rates or PFS, as compared to continuing with ABVD/AVD. We ackowledge that some bias may have impacted in the selection of escalation or maintaning ABVD in this population. However, since there is clear lack of data solely on Deauville 4 patients, we believe these results are of interest and should be evaluated in larger cohorts.