Mass spectrometry-based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma.

ABSTRACT: Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of posttransplant maintenance with either carfilzomib, lenalidomide, and dexamethasone, or with lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in the PB in the posttransplant setting, despite unavailability of pretreatment calibration samples. There was high agreement between MRD by MS in the PB and paired bone marrow (BM) MRD results at the 10-5 threshold, assessed by either next-generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which, in landmark analysis, reached statistical significance after 18 cycles after transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared with MRD negativity by only 1 modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, posttransplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.

Pfizer and Palbociclib in China: Analyzing an Oncology Pay-for-Performance Plan.

OBJECTIVES: China is poised to become the world's second-largest oncology drug market. Its ability to continue broadening health coverage is in question. Institutional innovations such as performance-based risk-sharing agreements (PBRSAs) have been developed to promote access to novel therapeutics beyond that provided by public health insurance and central procurement systems. We examine in depth the financial implications of a PBRSA developed in China for the breast cancer drug palbociclib. METHODS: We generated a 2-state Markov model from PBRSA information made publicly available. Model inputs included breast cancer outcomes data from the published literature. The primary analysis estimates the percentage reduction in overall drug expenditures due to the PBRSA. Sensitivity analyses explored the financial impact of varied computed tomography scan utilization, rebate rate, and rebate duration. RESULTS: Estimated palbociclib expenditures for the PBRSA cohort totaled $36 278 000. Based on the publicly available information for the PBRSA, an effective discount of 1.3% was estimated. The effective discount was insensitive to changes in computed tomography scan utilization. CONCLUSIONS: The palbociclib PBRSA likely had negligible impact on patient access to therapy and limited downstream financial impact to patients and payers. The short duration of the rebate window, small rebate, and disease indolence contributed to the low expected rebate percentage.