Real World Escalated BEACOPDac Delivers Similar Outcomes to Escalated BEACOPP While Potentially Reducing Haematopoietic and Reproductive Toxicity
When treating advanced stage Hodgkin lymphoma, it is common UK practice to modify escalated BEACOPP (eBPP) by removing oral procarbazine and replacing it with intravenous dacarbazine (250mg/m2 D2-3). This is a retrospective study of patients treated with first line escalated BEACOPDac (eBPDac) at 23 centres updated since ASH 2021. With a median follow-up of 28 months, the 24-month progression-free survival (PFS) is 95% (CI 92.2-98.0%).
Of 268 eBPDac patients, 226 were treated as per HD18 protocol and 42 as per AHL2011. Survival outcomes were compared with 2073 eBPP patients in the HD18 trial and 1088 patients aged 18-59y in the RATHL trial. The eBPDac patients were younger than the HD18 and RATHL patients but had higher risk and more stage 4 disease. Of the eBPDac patients 76% achieved iPET Deauville score (DS) ≤3, similar to RATHL (DS≤3:83.7%) and HD18 (DS≤3:76%). One patient had primary refractory disease and twelve have relapsed at 6 to 36 months. Three patients have died of non-lymphoma causes. The eBPDac 24-month PFS is similar to HD18 3-year PFS (95% vs 92.3%) and appears superior to RATHL 5-year PFS (81.4%). The difference in PFS between eBPDac and RATHL is most marked in IPS3+ patients. The eBPDac 24-month OS estimate is 99%.
Toxicity was compared between eBPDac patients and 68 matched real-world eBPP patients over the first 4 cycles. There were no significant differences in age, sex or stage, but more eBPP patients had high risk disease (IPS3+). Mean day 8 (D8) ALT was similar between the two regimens. Mean D8 neutrophil count was lower in eBPDac patients with D9 GCSF. eBPDac patients received fewer red cell transfusions compared with eBPP patients (mean 1.88 vs 3.83 units, p<0.001) and had fewer non-elective days of inpatient care (mean 3.49 vs 5.66; p=0.021). Of the women aged <35y who completed ≥4 cycles chemotherapy, 52/52 had return of menstrual periods after eBPDac, compared to 25/28 after eBPP. eBPDac patients appeared to restart menstruation earlier post chemotherapy (mean 4.71 vs 8.89 months, p=0.002). However, eBPP patients received more cycles of chemotherapy.
To compare haematopoietic stem cell toxicity, peripheral blood mononuclear cells were isolated from 4 eBPDac, 5 eBPP and 3 ABVD patients. Haematopoietic progenitor cells were grown in culture and the colonies harvested have undergone whole genome sequencing. The data is imminent and we will present the mutation burden and mutational signatures associated with these regimens.