Prehabilitation Exercise Training to Target Improved Muscle Strength in Pretransplant Patients Diagnosed With Multiple Myeloma: Protocol for a Pilot Randomized Controlled Trial.

Background: Muscle mass and strength are severely compromised in patients diagnosed with multiple myeloma, such that the risk of poor overall survival increases as the prevalence of low muscle mass, also known as sarcopenia, increases. Additionally, at the time of autologous stem cell transplant (ASCT), 51% of patients experience low muscle mass and strength, which can prolong hospitalization and lead to increased risk of obesity, insulin resistance, lowered physical function, and poor quality of life.

Objective: The PROTECT (Prehabilitation Exercise Training in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation) trial will examine the preliminary effects of digitally supervised prehabilitative aerobic and resistance exercise on muscle strength in patients with multiple myeloma scheduled for ASCT.

High-Valent Cobalt-Difluoride in Oxidative Fluorination of Saturated Hydrocarbons.

The heme paradigm where Fe=O acts as the C-H oxidant and Fe-OH rebounds with the formed carbon-centered radical guides the design of the prototypical synthetic hydroxylation catalyst. We are exploring methods to evolve beyond the metal-oxo oxidant and hydroxide rebound, to incorporate a wider array of functional group. We have demonstrated the application of CoII(OTf)2 (10 mol% catalyst; OTf = trimfluoromethanesulfonate) in combination with polydentate N-donor ligands (e.

Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer.

Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1.

Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma.

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial.

Allocation and validation of the second revision of the International Staging System in the ICARIA-MM and IKEMA studies.

The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab-pomalidomide-dexamethasone vs. pomalidomide-dexamethasone) and IKEMA (isatuximab-carfilzomib-dexamethasone vs.