Comparative effectiveness of different chemotherapy regimens of advanced-stage Hodgkin lymphoma in adults: a network meta-analysis

BACKGROUND: Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of the efficacy of different chemotherapy regimens in adults with advanced-stage HL. MATERIALS AND METHODS: We searched for relevant randomized controlled trials (RCTs) in titles/abstracts in PubMed, Embase, and the Cochrane Library. The search was last updated on April 3, 2018. RCTs that assessed the effectiveness of one of the following treatments were included: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); four cycles of increased dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP(escalated)) followed by two or four cycles of standard dose of BEACOPP (4× BEACOPP(escalated) + 2 or 4× BEACOPP(baseline)); brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD); doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (Stanford V); mechlorethamine (cyclophosphamide), vincristine, procarbazine, and prednisone (M[C] OPP); sequential or alternating chemotherapy regimens with ABVD as the footstone (eg, COPP/ABVD or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/ABVD); eight cycles of BEACOPP(escalated); hybrid MOPP/ABV; and M[C]EC (M[C]OPP with epidoxorubicin, bleomycin, vinblastine [EBV], and lomustine, doxorubicin, and vindesine [CAD]). RESULTS: Overall, we screened 3,564 citations and deemed 18 reports of 16 trials eligible and included them in our network meta-analysis. A total of 11,928 participants were randomly assigned to one of the 12 combinations of chemotherapy regimens, of which 11,476 participants were analyzed. For the overall survival (OS), no differences were observed within any interventions when the ABVD regimen was used as the reference treatment. Similarly, relative to A+AVD, 8× BEACOPP(escalated) and 6× BEACOPP(escalated) also showed no differences (HR =1.07, 95% credible interval (CrI): 0.58–1.95; HR =0.62, 95% CrI: 0.16–1.83; and HR =0.71, 95% CrI: 0.30–1.72, respectively). In terms of complete remission (CR), enough evidence exists to support a maximum clinical treatment effect for 6× BEACOPP(escalated) (OR =1.88, 95% CrI: 1.20–2.96; and OR =3.43, 95% CrI: 1.87–6.24). CONCLUSION: When compared across the 12 combined chemotherapy regimens, six cycles of BEACOPP(escalated) may be the optimal treatment for patients with advanced-stage HL.