Kinetics of response to first- and second-line therapies in multiple myeloma: Assessment by both M-spikes and light chains.

OBJECTIVES: The prognostic value of kinetics of response to multiple myeloma (MM) therapy is controversial. We aimed to expand the knowledge on this topic by reviewing the kinetics of response to both first- and second-line MM therapy, utilizing a homogeneously treated cohort and analyzing separately both M-spike and light chain (LC) responses for each patient. METHODS: We reviewed all patients who received first-line cyclophosphamide, bortezomib and dexamethasone induction followed by autologous transplant with melphalan and lenalidomide maintenance in our center between 2007 and 2019. RESULTS: Analyzing 360 patients, we observed no correlation between response kinetics to first- versus second-line therapy at the individual patient level. Time to best response to first-line therapy was not a predictor of outcome; however, longer time to best response was highly predictive of a favorable outcome in the second-line setting, independent of other factors. Patients with IgA-MM cleared their M-spike faster than IgG-MM, probably reflecting different half-lives of these isotypes rather than disease biology, as the clearance of LC in both subtypes was similar. CONCLUSIONS: Analyzing both M-spike and LC responses in a homogenously treated cohort, we identified important insights regarding the prognostic value of kinetic patterns. Prospective analysis may shed more light on unsolved questions.

A descriptive cost-analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.

BACKGROUND: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data. METHODS: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020). RESULTS: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange. CONCLUSIONS: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens.

Improving the Safety and Quality of Systemic Treatment Regimens in Computerized Prescriber Order Entry Systems.

PURPOSE: Systemic treatment (ST) computerized prescriber order entry (CPOE) and preprinted orders (PPO) are proven to reduce errors. There is no known guidance in oncology to facilitate high-quality, accurate regimen development and review; hence, this was identified as a system-wide gap. This provincial initiative aimed to improve the quality of oncology regimens through a comprehensive review of systemic treatment (ST) regimens and the development of standards. METHODS: A system-wide analysis of all active regimens (both CPOE and PPO) to ensure they were built as intended was conducted in 2015. Thirty-five hospitals (on behalf of 75 treatment facilities) were asked to report any unintentional discrepancies and details of the maintenance review process. Discrepancies were compiled, categorized, and analyzed for potential to cause harm. In addition, a multidisciplinary expert working group was formed to create best practice recommendations. RESULTS: The review yielded a 94% response rate and took a total of 18 months to complete (70% completed within 9 months). The average number of regimens reviewed was 336 (range, 15 to 700; n = 9). Unintentional discrepancies were reported by nine hospitals (27%). A total of 369 discrepancies were reported (average, 55 per hospital), and 28 were deemed to have a moderate potential for harm. Only two hospitals (6%) had an established maintenance process; now, all have standard processes for review. Consensus-based recommendations for ST-CPOE and PPO regimen development and maintenance were developed. CONCLUSION: The review identified unintentional discrepancies and, because of the potential for patient harm, corrective action has been taken. Identified discrepancies have been amended, and standard regimen development and maintenance review processes are now implemented system-wide to improve the quality and safety of systemic treatment delivery.

Gemcitabine/dexamethasone/cisplatin vs cytarabine/dexamethasone/cisplatin for relapsed or refractory aggressive-histology lymphoma: cost-utility analysis of NCIC CTG LY.12.

BACKGROUND: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. METHODS: The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. RESULTS: The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. CONCLUSIONS: GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.