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Percentage Change from Baseline (PCB) for B-cells (CD19+) and Immunoglobulins (Ig)at 20-day time intervals post-baseline.

Percentage Change from Baseline (PCB) for B-cells (CD19+) and Immunoglobulins (Ig)at 20-day time intervals post-baseline.

Bortezomib pharmacokinetic parameters following a single intravenous 1.3 mg/m2 bolus dose and varying single intravenous doses of tabalumab

Bortezomib pharmacokinetic parameters following a single intravenous 1.3 mg/m2 bolus dose in the presence or absence of tabalumab and dexamethasone

Purpose: Tabalumab, a human mAb that neutralizes B-cell–activating factor (BAFF), demonstrated antitumor activity in xenograft models of multiple myeloma. Here we report on a phase I study of relapsed/refractory multiple myeloma patients in which the primary objective was to identify a tolerable and potentially efficacious dose of tabalumab when combined with bortezomib.Experimental Design: Forty-eight patients were enrolled; 20 to the dose-escalation cohort, and 28 to cohort expansion in which a dose of 100 mg of tabalumab was evaluated. All patients had received either prior bortezomib or an immunomodulatory drug; the median number of prior therapies was 3. Bortezomib was administered intravenously on days 1, 4, 8, and 11 of a 21-day schedule. Tabalumab was given every 21 days for 3 cycles, then every 42 days thereafter.Results: The most common grade 3/4 toxicities included thrombocytopenia, neutropenia, pneumonia, and peripheral sensory neuropathy. There were no dose-limiting toxicities, and the maximum tolerated dose was not reached. Pharmacokinetic data suggested serum exposure increased in a greater than dose-proportional manner up to a dose of 100 mg. Out of 46 evaluable patients, 20 had confirmed responses. The median time to progression (9 patients censored) was 4.8 months, and the median response duration (4 patients censored) was 7.2 months.Conclusions: A dose of 100 mg tabalumab in combination with bortezomib was well tolerated and active and is currently under further investigation. Clin Cancer Res; 22(23); 5688–95. ©2016 AACR.

Pharmacokinetic parameters of tabalumab in multiple myeloma patients

Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.

CAR-T therapies represent a novel advance in oncology, albeit at list prices that exceed $373,000 (and that does not capture their total cost to the healthcare system). Since initial product approval in 2017, stakeholders and observers have attempted to investigate clinical and financial impacts of CAR-T therapies, and potential approaches to optimizing access and use by eligible patients. Most existing research is from a single stakeholder perspective - patients, providers, or payers - limiting the ability to draw broader conclusions on trends and offer prospective recommendations. To address this knowledge gap, we sought to identify and describe critical success factors for optimal delivery of CAR-T therapies. We undertook a qualitative study based on interviews with multiple US-based stakeholders including clinicians, financial and operations staff, and payer-insurers. Interviewees--which included oncologists (n=6), facility financial and operational personnel (n=4), and coverage and reimbursement decision-makers from US health plans (n=3)--completed structured, live, hour-long, interviews covering clinical, administrative, and general topics on patient access to CAR-T therapies. All clinicians had experience with ≥1 FDA-approved CAR-T therapies in both registered clinical trials and clinical practice; financial and operational personnel were affiliated with the same facilities as the clinicians, and also had real-world experience with these therapies; payer representatives were directors from a large national commercial plan, regional integrated delivery network, and a Medicare administrative contractor, respectively. Consensus facility feedback (i.e., clinicians, operational personnel) was that CAR-T is effective, and that their administrative processes had been optimized through care team coordination and experience-based efficiencies; in contrast, 2 of 3 payer interviewees expressed that, while CAR-T therapies have shown efficacy, their real-world benefits and applicability are less well-defined. Facility interviewees noted that: (1) reimbursement from commercial insurers is higher than from Medicare, with the latter associated with per-patient net-neutral or negative margins; (2) when possible, differential reimbursement between inpatient and outpatient settings may drive patient management towards outpatient care; and (3) negative-margin cases are currently deemed acceptable due to nonclinical factors (i.e., competitive pressure within a geographic region, anticipated branding/marketing value) and relatively small treated populations. From payer interviewees, CAR-T cost and perceived cost-to-value have made health plans more receptive to considering outcomes-based contracting, capitated provider payments, or other mitigation methods. Left unoptimized, these factors may adversely impact patient access to, and long-term provider attractiveness of, CAR-T therapies. All interviewees agreed that as the CAR-T marketplace grows, a strong preference exists for manufacturers to develop and communicate for their therapies durable outcomes data, clear and comprehensive reimbursement information, and competitive pricing. With the potential for many approved products in a single indication, and/or a single approval for indications with relatively large eligible patient populations, interviewees also conveyed interest in compelling health economic data. Facility interviewees also acknowledged that if it remains an overall net-negative margin service, new providers will be less able to start CAR-T programs and smaller programs may encounter sustainability issues, collectively jeopardizing patient access to these life-changing therapies. Overall, findings from this study suggest that during the continued maturation of the landscape, stakeholders will need to be proactive to ensure that CAR T-cell therapies can be maintained amidst financial and operational pressures. Several CAR-T therapy options for multiple myeloma are on the immediate horizon, likely increasing demand among eligible patients. Accordingly, the need to link real-world evidence of the clinical value and institutional investment burden of these therapies to reimbursement is imperative, both to insulate payers and enable clinicians to provide innovative therapies. Figure 1 Figure 1. Disclosures Faber: Amgen: Honoraria; Adaptive: Honoraria; Cardinal Health: Honoraria; Celgene: Honoraria; Astra Zeneca: Honoraria; GlaxoSmith Kline: Honoraria; Janssen: Honoraria; Juno: Honoraria; Karyopharm: Honoraria; Kite: Honoraria; Takeda: Honoraria; Sanofi Genzyme: Honoraria. Hunter: BMS: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Deol: Kite, a Gilead Company: Consultancy. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Riccobono: Legend Biotech: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Garrett: Legend Biotech USA: Current Employment. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Fowler: Amgen: Ended employment in the past 24 months; Janssen: Current Employment. Berger: Janssen Scientific Affairs: Consultancy, Research Funding. Lorden: Janssen Scientific Affairs: Consultancy, Research Funding. Stewart: Janssen Scientific Affairs: Consultancy, Research Funding.