Intensive frontline therapy followed by consolidation radiotherapy to residual disease may lead to improved progression-free survival (PFS) and overall survival (OS) in patients with Hodgkin lymphoma (HL), according to results published in The Lancet Haematology.
Intensified chemotherapy regimens have been shown to improve survival and tumor control in advanced stage HL. In this preplanned analysis, researchers assessed long-term follow-up data on the primary survival benefits experienced by patients who participated in the German Hodgkin Study Group’s HD9 and HD12 clinical trials.
The HD9 trial, which ran from 1993 to 1998, included 1282 patients with newly diagnosed, histology-confirmed, advanced stage HL who underwent 8 alternating cycles of cyclophosphamide, vincristine, procarbazine, and prednisone and doxorubicin, bleomycin, vinblastine, dacarbazine (COPP/ABVD), 8 cycles of a baseline-dose regimen of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (bBEACOPP), or 8 cycles of an escalated-dose version of BEACOPP (eBEACOPP). The HD12 trial, which ran from 1999 to 2003, included 1670 patients with newly diagnosed, histology-confirmed, advanced stage HL who underwent 8 cycles of eBEACOPP or 4 cycles of eBEACOPP plus 4 cycles of bBEACOPP (4 + 4), plus consolidation radiotherapy to initial bulk and residual disease or no radiotherapy. Both trials were centrally randomized. Treatment was open label.
After a median observation time of 141 months in HD9, 15-year PFS was 57.0% (95% CI, 50.0-64.0) for COPP/ABVD, 66.8% (95% CI, 61.9-71.8) for bBEACOPP, and 74.0% (69.0-79.0) for eBEACOPP. Fifteen-year OS was 72.3% (95% CI, 66.5-78.1) for COPP/ABVD, 74.5% (95% CI, 70.1-78.9) for bBEACOPP, and 80.9% (95% CI, 76.7-85.0) for eBEACOPP.
PFS and OS in HD9 remained significantly higher in the eBEACOPP cohort than in the COPP/ABVD cohort (P <.0001 and P =.015, respectively). The 15-year cumulative incidence of second primary malignant neoplasms was 7.2% (95% CI, 3.7-10.7) after COPP/ABVD, 13.0% (95% CI, 9.1-16.9) after bBEACOPP, and 11.4% (95% CI, 7.6-15.1) after eBEACOPP
After a median observation time of 97 months (IQR, 69-143) in HD12, 4 + 4 was noninferior to eBEACOPP alone, with a 10-year PFS of 82.6% (95% CI, 79.6-85.6) for eBEACOPP and 80.6% (95% CI, 77.4-83.7) for 4 + 4 (hazard ratio = 1.13, within non-inferiority margin of 1.50). The 10-year OS was 87.3% (95% CI, 84·7-89·9) for eBEACOPP and 86.8% (95% CI, 84.2-89.4) for 4 + 4 (HR = 1.02).
In the 37% of patients in HD12 who had residual disease after chemotherapy, not undergoing radiotherapy was associated with inferior 10-year PFS (83.4% [78.2-88.5] for no radiotherapy vs 89.7% [95% CI, 85.8-93.6] for radiotherapy; P =.027) and inferior 10-year OS (88.4% [95% CI, 83.8-93.0] for no radiotherapy vs 94.4% [95% CI, 91.4-97.3]; P =.025). The 10-year cumulative incidence for second primary malignancies was 6.4% (95% CI, 3.3-9.5) for 4 + 4 and 8.8% (95% CI, 5.2-12.4) for eBEACOPP.
“The results of our analysis suggest that the tradeoff between efficacy and toxicity in advanced stage HL favors the use of eBEACOPP followed by radiotherapy,” though late-stage toxicities, including second primary malignancies, contribute to overall mortality, the authors concluded.
1. von Tresckow B, Kreissl S, Goergen H, et al. Intensive treatment strategies in advanced-stage Hodgkin’s lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials [published online October 2, 2018]. Lancet Haematol. doi: 10.1016/S2352-3026(18)30140-6