First-Line N-AVD Delivery Strategy Does Not Substantially Affect Outcome In Early cHL

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: First-line treatment with the programmed cell death (PD)-1 inhibitor nivolumab plus doxorubicin, vinblastine, and dacarbazine chemotherapy (N-AVD) is effective whether given concomitantly or sequentially to patients with stage I or II unfavourable classic Hodgkin lymphoma (cHL), results of the phase II NIVAHL trial show. 

Despite the data for the concomitant group narrowly missing the efficacy cutoff, the researchers say: “Anti–PD-1-based first-line treatment of early-stage cHL warrants further evaluation within future trials, comparing a fully concomitant treatment with standard of care or an individualized approach with sequential anti–PD-1 treatment guided, eg, by interim [positron-emission tomography]”. 

Andreas Engert, from the University Hospital of Cologne in Germany, and colleagues found that the complete remission (CR) rate was 90% among 51 patients randomly assigned to receive four cycles of concomitant N-AVD, given on days 1 and 15 of each 28-day cycle, followed by consolidating treatment with 30 Gy of involved-site radiotherapy. 

By comparison, the CR rate was 94% among 50 patients randomly assigned to receive sequential therapy beginning with four infusions of nivolumab at 14-day intervals followed by two 28-day cycles of N-AVD and two 28-day cycles of AVD, then radiotherapy. 

However, the lower 95% confidence interval of 79% observed in the concomitant group fell just short of prespecified efficacy cutoff of 80%. It was 84% in the sequential group. 

Treatment compliance rates were high, with 80% and 91% of patients in the concomitant and sequential groups, respectively, receiving the preplanned eight infusions of nivolumab and 91% and 89%, respectively, receiving four full cycles of N-AVD. 

And interim analysis conducted after two cycles of N-AVD or four doses of nivolumab monotherapy showed a high degree of early responses, with CR rates of 87% and 51% in the concomitant and sequential groups, respectively. 

After a median follow-up of 13–14 months, the 12-month progression-free survival was 100% among the patients who received concomitant treatment and 98% among those who received sequential therapy. Overall survival at 12 months was 100% in both groups. 

Treatment-related adverse events (AEs) of grade 3 or higher were reported in 76% and 80% of patients in the concomitant and sequential groups, respectively. These typically comprised haematological AEs, which occurred in 71% and 65%, respectively, while organ-related AEs occurred in a corresponding 24% and 30%. Serious adverse events occurred in 38% of the concomitant group and 28% of the sequential group.  

Andreas Engert and co-authors comment in JAMA Oncology: “While we conclude excellent short-term disease control, the long-term efficacy and curative potential as well as potential late effects of both treatment strategies are to be determined with the designated longer follow-up of 3 years within the NIVAHL trial.” 

Reference  

Bröckelmann PJ, Goergen H, Keller U et al. Efficacy of nivolumab and AVD in early-stage unfavorable classic Hodgkin lymphoma. The randomized phase 2 German Hodgkin Study Group NIVAHL trial. JAMA Oncol; Advance online publication 30 April 2020. doi:10.1001/jamaoncol.2020.0750