Lead Investigator: Yi Lisa Hwa, Mayo Clinic
Title of Proposal Research: Better outcomes among multiple myeloma patients who are taking beta-blockers while receiving chemotherapy.
Vivli Data Request: 8442
Funding Source: None
Potential Conflicts of Interest: Yi Lisa Hwa reports: Sanofi – September 2020 Multiple Myeloma Virtual Advisory Board
Akcea Therapeutics – March 2021 Virtual hATTR Amyloidosis National Nurse Practitioner Advisory Board
This study is not funded by Sanofi. Sanofi has agreed to let researchers access to the trial data to do additional analysis and evaluate the potential effect of beta blocker on treatment outcome in myeloma patients.
Researcher participated a virtual advisory board meeting in 2020, which is unrelated to this current project. Author will declare this in subsequent publications.
Angela Dispenzieri reports: Research funds: Alnylam, Celgene/BMS, Takeda, Pfizer.
Consulting: Janssen, Oncopeptides and Regeneron
No potential conflicts of interests with this project. This study is not funded by Sanofi. Sanofi has agreed to let researchers access to the trial data to do additional analysis and evaluate the potential effect of beta blocker on treatment outcome in myeloma patients.
Summary of the Proposed Research:
Background: The anti-cancer effect of beta blockers (BB), a class of medications predominately used to treat a range of cardiac issues, has been reported in a variety type of solid tumors but understudied in hematologic malignancies (diseases of the blood). Multiple myeloma (MM) is a type of blood cancer when a group of plasma cells in the bone marrow becomes cancerous. This disease can damage normal blood cells, immune system, kidneys and bones. We are the first group to report that BB improved treatment outcome in patients with multiple myeloma.
Proposed Study: Because of the encouraging findings of our two previous studies and the convincing literature evidence of the potential antitumor mechanism of BB, we are hoping to conduct a sub-analysis of data from the clinical trials sponsored by Sanofi to further explore the potential interactions of BB with MM therapies.
Proposed Methods: We would like to retrospectively review data from the clinical trials of isatuximab in combination of pomalidomide / dexamethasone or carfilzomib / dexamethasone provided by Sanofi. Pomalidomide is the newest iteration of immunomodulatory drugs that was approved by the Food and Drug Administration (FDA) to treat relapsed multiple myeloma. Dexamethasone, the most commonly used steroid in multiple myeloma therapy, is included in most of the treatment regimens. Carfilzomib is the second-generation of proteasome inhibitors that therapeutically block the function of proteasomes (cellular complexes that breakdown protein), therefore disrupting the protein metabolism of myeloma cells. We plan to extract the use of BB and non-BB cardiac or antihypertensive medication history to include the first and last documented date of BB and or other non-BB medications, dosage, and duration. BB use is defined as a minimum of 3 months of BB intake during trial participation. Progression free survival (PFS), time to progression (TTP), and overall survival (OS) will be the endpoints to compare the outcomes between BB and non-BB usage groups. If possible, we would like to study if these same endpoints are affected by the dosage and duration of BB administration. PFS is defined as the time from initiating the clinical trial to the time of disease progression or death. Overall survival is calculated as the time from the date of diagnosis to the date of death. Time to progression is measured as the length of time from initiating clinical trial to disease progression. The International Myeloma Working Group (IMWG) has defined disease progression as having at least one of the following: a 25% increase in serum monoclonal protein with an absolute increase of at least 0.5 g/dL; urine monoclonal protein with an absolute increase of at least 200 mg / 24 hours; an absolute increase in urine monoclonal protein in patients without measurable serum and urine monoclonal protein levels; bone marrow clonal plasma cell percentage of at 10%; new bone lytic lesions or soft tissue plasmacytoma.
A Phase 3 Randomized, Open-label, Multicenter Study Comparing Isatuximab (SAR650984) in Combination With Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Data Contributor: Sanofi
Study ID: NCT02990338
Sponsor ID: EFC14335