OBJECTIVES:

Inotuzumab ozogamicin (InO) is an anti-CD22 antibody-calicheamicin conjugate that has demonstrated superior efficacy in patients with r/r B-ALL compared to IC in the pivotal Phase III INO-VATE ALL trial. A UK-based Markov model has been developed based on this study to estimate the mean life year (LY) and QALY gains associated with InO compared to IC. Using a 1.5% discount rate, we explored key QALY drivers and factors influencing long-term survival following haematopoietic stem cell transplant (HSCT).

METHODS:

Using trial data, parametric survival curves were generated based upon patient’s remission status and whether they received a HSCT. Patients alive 3 years post-HSCT were considered cured and followed general population mortality. Utilities were based on trial EQ-5D scores, and utilities for both post-HSCT and progression states were from the literature.

Three scenarios were used to explore post-HSCT survival: (1) using the INO-VATE ALL post-HSCT data split by treatment to estimate treatment effect; (2) pooling the data from both treatment arms and applying survival post-HSCT independent of treatment; and (3) applying a covariate for minimal residual disease negativity, which was shown to be key in determining long-term post-HSCT survival in the treatment of de novo disease and is under investigation as a prognostic factor for survival following relapse.

RESULTS:

InO increased survival by 5.18 LYs and 2.23 QALYs versus IC. One-way sensitivity analysis showed utility values in progressive disease and those used 5 years post-HSCT to be most influential. Probabilistic sensitivity analysis showed a large spread in QALYs gained which was a result of post-HSCT survival estimates. The first post-HSCT scenario indicated the largest LY and QALY gains for InO in comparison to IC.

CONCLUSIONS:

InO was shown to increase survival and QALYs compared to IC demonstrating it to be an effective treatment for r/r B-ALL; this was demonstrated in all three scenarios explored post-HSCT.