Dinutuximab Beta vs. Historical Controls in the Maintenance Therapy of Relapsed Neuroblastoma: Unadjusted and Adjusted Indirect Comparison
Author(s)
Holger N. Lode, PhD, MD1, Przemyslaw Holko, PhD2, Katarzyna Sladowska, PhD3, Pawel Kawalec, PhD, MD4, Fabian Schmidt, MA, MBA5.
1University Medicine Greifswald, Greifswald, Germany, 2Jagiellonian University Medical College, Kraków, Poland, 3Jagiellonian University Medical College, Krakow, Poland, 4Jagiellonian University, Kraków, Poland, 5Recordati Rare Diseases Sarl, Puteaux, France.
1University Medicine Greifswald, Greifswald, Germany, 2Jagiellonian University Medical College, Kraków, Poland, 3Jagiellonian University Medical College, Krakow, Poland, 4Jagiellonian University, Kraków, Poland, 5Recordati Rare Diseases Sarl, Puteaux, France.
OBJECTIVES: Dinutuximab beta (DB) is the only anti-GD2 immunotherapy approved for maintenance treatment of both newly diagnosed and relapsed/refractory neuroblastoma (RRNBL). Approval of this orphan therapy in RRNBL was based on early data from two small clinical studies demonstrating overall survival (OS) benefit. We aimed to re-evaluate this benefit using a wider body of evidence currently available.
METHODS: Individual patient data from prospective (APN311-202; APN311-304) and retrospective (APN311-303) studies of DB identified in a systematic literature review and from historical controls (HC) (prospective R1 and retrospective INBR) were pooled from study reports. Indirect, unanchored naïve comparison (unadjusted), as well as population-adjusted comparison using inverse probability weighting (IPW), were conducted. Harmonized inclusion criteria were applied to all study populations. Propensity score (PS) reweighting was used to balance populations on key prognostic factors: age, age at diagnosis, time from diagnosis, sex, MYCN status and INSS stage. Multiple Cox model was used to verify results of the PS IPW model. The starting point for OS analyses was initiation of DB treatment. Since historical control patients had not been treated with DB, an auxiliary starting point was estimated from the date of the last relapse.
RESULTS: Pooling yielded 144 DB and 82 HC relapsed patients. In the base-case unadjusted indirect comparison DB (±interleukin-2) significantly extended OS compared to HC (hazard ratio [HR] with 95% confidence interval [CI] was 0.43 [0.31; 0.79], p<0.001). Similarly, base-case adjusted indirect comparison using PS reweighting revealed that DB significantly extended OS (HR [95% CI]=0.53 [0.35; 0.79], p=0.002). In the Cox model HR was 0.51 (95% CI: 0.35 to 0.73, p<0.001). All sensitivity analyses, unadjusted and adjusted, including use of DB without interleukin-2, supported the results of the base-case.
CONCLUSIONS: Dinutuximab beta significantly extends overall survival in relapsed neuroblastoma compared to disease not treated with immunotherapy - in both unadjusted and adjusted indirect comparisons.
METHODS: Individual patient data from prospective (APN311-202; APN311-304) and retrospective (APN311-303) studies of DB identified in a systematic literature review and from historical controls (HC) (prospective R1 and retrospective INBR) were pooled from study reports. Indirect, unanchored naïve comparison (unadjusted), as well as population-adjusted comparison using inverse probability weighting (IPW), were conducted. Harmonized inclusion criteria were applied to all study populations. Propensity score (PS) reweighting was used to balance populations on key prognostic factors: age, age at diagnosis, time from diagnosis, sex, MYCN status and INSS stage. Multiple Cox model was used to verify results of the PS IPW model. The starting point for OS analyses was initiation of DB treatment. Since historical control patients had not been treated with DB, an auxiliary starting point was estimated from the date of the last relapse.
RESULTS: Pooling yielded 144 DB and 82 HC relapsed patients. In the base-case unadjusted indirect comparison DB (±interleukin-2) significantly extended OS compared to HC (hazard ratio [HR] with 95% confidence interval [CI] was 0.43 [0.31; 0.79], p<0.001). Similarly, base-case adjusted indirect comparison using PS reweighting revealed that DB significantly extended OS (HR [95% CI]=0.53 [0.35; 0.79], p=0.002). In the Cox model HR was 0.51 (95% CI: 0.35 to 0.73, p<0.001). All sensitivity analyses, unadjusted and adjusted, including use of DB without interleukin-2, supported the results of the base-case.
CONCLUSIONS: Dinutuximab beta significantly extends overall survival in relapsed neuroblastoma compared to disease not treated with immunotherapy - in both unadjusted and adjusted indirect comparisons.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO74
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology, Rare & Orphan Diseases