Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs). OBJECTIVE: To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs. METHODS: Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations. RESULTS: Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, respectively). CONCLUSION AND RELEVANCE: Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively.

Plerixafor strategies for autologous hematopoietic cell transplant mobilization: A comparison of efficacy and cost.

Addition of plerixafor (P) to granulocyte colony stimulating factor (G-CSF) during peripheral blood mobilization of hematopoietic stem cells (HSC) increases the number of patients meeting collection goals prior to autologous stem cell transplant (aSCT). However, use of P is not universal among transplant centers due to cost. This study aims to compare clinical and financial impacts of using an algorithm-based P mobilization strategy versus use in all patients. This was a single center, retrospective analysis of adult patients with myeloma or amyloidosis receiving aSCT who received apheresis of their HSC between 3/1/2017 and 3/1/2019. Patients prior to 3/1/2018 were classified as receiving P "per algorithm" and those after this date were classified as "up-front" P. For the per-algorithm group, P was given for a pre-apheresis CD34+ cell count of <20 cells/µL on mobilization day 5 and patients returned on day 6 for apheresis. Of the 129 patients included, 55 received P per-algorithm and 74 received up-front P. There was a reduction in median number of apheresis days (1.5 vs 1 day, p < 0.001) and an increase in median number of CD34+ cells collected (6.6 vs 8.5 × 106 cells/kg, p < 0.001) with up-front P. Up-front P increased drug cost but reduced apheresis costs, which resulted in a net savings of $121 per patient in total mobilization costs. These findings suggest that use of up-front P for mobilization significantly reduces apheresis days and increases HSC collection yield without increasing overall cost per patient.

Evaluation of gravimetric-based technology-assisted workflow for nonhazardous sterile product preparation.

PURPOSE: The impact of a gravimetric-based technology-assisted workflow (TAWF) system on the nonhazardous compounded sterile product (CSP) error capture rate, production times, and pharmacy staff perceptions of compounding methods was evaluated. METHODS: For 2 weeks prior to TAWF implementation, staff used a punch clock to document production times with a volumetric method. Preimplementation error data were captured in a previous study; TAWF software captured error and time data in the postimplementation period. An online staff survey was administered before and 90 days after TAWF implementation to evaluate perceptions of the 2 methods. RESULTS: The error capture rates were 0.47% in the preimplementation period and 41.48% in the postimplementation period. The median time to prepare CSPs was significantly shorter in the preimplementation period versus the postimplementation period (p < 0.0001). The median time to check CSPs was significantly shorter at both 90 days (p < 0.0001) and 180 days (p = 0.0006) after TAWF implementation. When asked if the current method was the safest and the most accurate method for preparation, staff members' perceptions improved from neutrality to agreement when the TAWF was implemented. Staff members were in agreement that the volumetric method was faster than the gravimetric TAWF method but were neutral as to whether the latter was the preferred compounding method. CONCLUSION: The study results indicated that gravimetric-based TAWF preparation of nonhazardous CSPs is slower than manual volumetric preparation but can improve the error capture rate. Staff perceived the gravimetric TAWF method to be the safest and most accurate for producing CSPs.