Leukemia & Lymphoma | 2019
Inotuzumab ozogamicin versus FLAG-Ida in the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia – real-world resource use data
Abstract
In June 2017, Inotuzumab ozogamicin (IO), a humanized anti-CD22 monoclonal antibody conjugated to a cytotoxic antibiotic agent calicheamicin [1], was approved by the European Medicines Agency (EMA) for treating adults with Philadelphia chromosome positive and negative relapsed or refractory CD22-positive B-cell acute lymphoblastic leukemia (ALL). The pivotal phase 3, randomized controlled INO-VATE 1022 trial (n1⁄4 326) demonstrated a significantly higher complete remission rate (80.7% versus 29.4%, p< .001) and longer duration of remission (4.6months versus 3.1months, p1⁄4 .03) in the IO group compared with the standard therapy group (fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG)-based combination chemotherapy, high-dose cytarabine, or cytarabine with mitoxantrone) in treating relapsed and refractory ALL [2]. IO has recently been recommended by the National Institute for Health and Care Excellent (NICE) [3] for U.K. practice with the real-world data collected having been taken into account in the economic analysis. In the adoption of novel agents, the cost of the agent and overall survival of the patients are the predominant considerations for reimbursement decisions. However, other advantages for patients and healthcare facilities, such as toxicity reduction, ease of administration, reduction in length of stay and a reduction in supportive care needs can be considerable. Clinical trials exhaustively document adverse events and such pivotal international registration studies provide the critical evaluations by which regulatory agencies make decisions. However, data which predict the overall impact of a novel approach in a particular healthcare system are rarely collected in such trials and are often not available for consideration at the time of reimbursement decisions. We aimed to determine whether IO conferred advantages for UK patients and the NHS in terms of length of stay and toxicity reduction, compared to salvage chemotherapy. We collected “real-world” data on resource usage in two centers – University College London Hospital and University Hospitals Bristol, which had enrolled patients to the IO compassionate use program. We analyzed data from all consecutive patients who had received IO and compared it with consecutive patients who had received FLAG-Ida, the most commonly used salvage regimen in ALL which, without the Idarubicin, had been the comparator in the pivotal study. We identified forty patients aged between 14 and 71 years who had received one or more cycles of either IO (one cycle contains 3 doses, given at weekly intervals) or FLAG-Ida chemotherapy for relapsed or primary refractory B precursor ALL between August 2008 and December 2017 in University College London Hospital or University Hospitals Bristol. Patient characteristics, including disease status at the time of treatment, number of previous lines of therapy and number of IO or FLAG-Ida cycles received were recorded. We also extracted data on length of inpatient stays, defined as admissions for one or more nights to a hospital bed. Data on infective complications and blood product usage in the 30 days immediately following the first dose of therapy were also extracted from our electronic records. Statistical analysis was by chi-squared or Mann–Whitney U-test. Patient characteristics are shown in Table 1. The patients were a relatively young but very heavily pretreated group. The IO and FLAG-Ida groups were reasonably well, but not completely, matched. The only statistically significant difference was that 5 of 17 (29%) IO recipients had received prior allogeneic stem cell transplant (alloSCT), compared to none of the 23 FLAGIda recipients. The IO group had also received more prior lines of therapy than the FLAG-Ida group, with 7 of 17 (41%) being on their third or fourth line of therapy whereas no FLAG-Ida recipient had received more than two prior lines of therapy, but these differences were not statistically significant.