As reported in the Journal of Clinical Oncology by Bröckelmann et al, final results of the German Hodgkin Study Group phase II NIVAHL trial indicate nearly 100% progression-free survival and 100% overall survival at 3 years among patients with early-stage unfavorable classical Hodgkin lymphoma receiving first-line concomitant or sequential regimens of nivolumab combined with doxorubicin, vinblastine, and dacarbazine (N-AVD) and consolidative radiotherapy.
The previously reported primary analysis of the trial indicated a complete remission rate (primary endpoint) of 92% among all study patients, with “an unprecedented” 1-year progression-free survival.
Study Details
In the investigator-sponsored open-label multicenter trial, 109 patients were randomly assigned to concomitant treatment with four cycles of N-AVD (n = 55) or sequential treatment with four cycles of nivolumab, two cycles of N-AVD, and two cycles of AVD (n = 54), followed in both groups by consolidation with 30 Gy of involved-site radiotherapy. The preplanned final analysis was conducted 3 years after registration of the last patient.
Key Findings
With a median follow-up of 41 months, no progression-free or overall survival events were observed since the primary analysis. In the entire population, estimated 3-year progression-free survival and overall survival were 99% (95% confidence interval [CI] = 97%–100%) and 100%.
In the concomitant-treatment group, estimated 3-year rates were 100% for both progression-free and overall survival. In the sequential-treatment group, estimated 3-year rates were 98% (95% CI = 95%–100%) for progression-free survival and 100% for overall survival.
One patient receiving sequential treatment experienced disease progression during nivolumab monotherapy. After continuing treatment with the standard two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine, and 30 Gy of involved-site radiotherapy, the patient remained alive and in complete remission at last follow-up at 34.7 months after the progression event.
Among all patients at last follow-up, respiratory disorders were reported in 19% of patients; these were mostly grade 1 (90%) and transient respiratory tract infections (89% resolved or improved at last follow-up). The mean forced expiratory pressure in 1 second was 95.5% (standard deviation [SD] = 12.7%), mean diffusion capacity for carbon monoxide adjusted for hemoglobin was 82.8% (SD = 15.4%). No cardiac events greater than grade 1 were reported during follow-up, and left ventricular ejection fractions were in the normal range in 95% of patients at last follow-up.
Hypothyroidism requiring long-term medication occurred in 15% of patients, of whom 87% were female. Any treatment for potentially treatment-related adverse events was required in 15% of patients, with none requiring immunosuppressant treatment. No second primary malignancies were observed. Patient-reported normalized global quality-of-life scores on the EORTC Quality of Life Questionnaire C30 improved over time.
The investigators concluded: “This preplanned [follow-up] analysis of the largest anti–programmed death protein 1 [Hodgkin lymphoma] first-line trial to date confirms the outstanding efficacy and relatively favorable safety profile of this therapeutic approach.”
Paul J. Bröckelmann, MD, Department I of Internal Medicine, University Hospital of Cologne, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
