An updated three-year analysis confirmed the efficacy and relatively favorable safety profile of nivolumab as a frontline treatment for patients with early-stage, unfavorable Hodgkin lymphoma (HL). There were no deaths among patients in the study, and the three-year progression-free survival (PFS) and overall survival (OS) rates were 99% and 100%, respectively, according to results of the phase II NIVAHL study presented at the 64th ASH Annual Meeting and Exposition.
“Anti-PD1 [programmed cell death protein 1] blockade is increasingly investigated as a first-line treatment for HL. Thoroughly evaluating safety, efficacy, and patient-reported outcomes is crucial in this indication due to high cure rates with conventional treatment approaches,” said presenter Paul Bröckelmann, MD, of the German Hodgkin Study Group (GHSG) and the University of Cologne in Germany. “The final analysis of this investigator-sponsored, multicenter, randomized GHSG NIVAHL trial provides these important data with a median follow-up of 41 months in the largest study available to date.”
The anti-PD1 antibody nivolumab has been investigated as either a sequential or concurrent therapy for patients newly diagnosed with HL showing high response rates and shorter term PFS. Yet, data on long-term efficacy, safety, and patient quality-of-life (QoL) has been lacking.
The NIVAHL study enrolled 109 patients ages 18 to 60 across 28 GHSG sites in Germany. Patients received either four concurrent cycles of nivolumab plus a standard chemotherapy combination of doxorubicin, vinblastine, and dacarbazine (4×N-AVD) or two sequential cycles of nivolumab monotherapy followed by two cycles of nivolumab plus chemotherapy (2×N-AVD) followed by 2×AVD. All patients subsequently received 30 Gy involved-site radiotherapy.
None of the patients who had a partial remission required further treatment, and all seven of these patients converted to an ongoing complete remission during the follow-up period.
“With [such high] PFS and OS estimates, a relevant proportion of patients might not require the cumulative, still quite intensive treatment with a total of eight cycles of nivolumab and four cycles of AVD followed by 30 Gy radiotherapy (IS-RT),” Dr. Bröckelmann added.
The addition of nivolumab to standard chemotherapy appeared to be relatively well tolerated and was also associated with improved global QoL compared to pre-treatment measurements. There were no second primary malignancies reported during the median 40 months of follow up, and no relevant decline in cardiac or pulmonary function was observed.
Fifteen percent of patients developed persisting hypothyroidism during follow-up and required ongoing treatment at data cut-off. No patient required long-term corticosteroid treatment as of the last follow-up. This long-term side effect of the therapy was almost exclusively observed among women.
“This usually irreversible immune-related side effect needs to be taken into account when further developing anti-PD1-based first-line HL treatment and [when] counseling patients,” Dr. Bröckelmann noted.
“Upcoming trials will investigate more individualized, response-adapted anti-PD1 treatment of [HL] to optimally balance risks and benefits of treatment intensity and also enroll patients age 60 and older to understand the optimal use of anti-PD1 antibodies in this growing population,” Dr. Bröckelmann said.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Bröckelmann PJ, Bühnen I, Meissner J, et al. Nivolumab and AVD in early-stage unfavorable Hodgkin lymphoma: follow-up analysis of the randomized GHSG phase II NIVAHL Trial. Abstract #729. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 12, 2022; New Orleans, Louisiana.