Mosunetuzumab-axgb (Lunsumio™)

What is mosunetuzumab-axgb? Mosunetuzumab-axgb is a bispecific antibody CD20-directed CD3 T-cell engager. This first-in-class, T cell-engaging, bispecific antibody binds to the CD3 receptor on T-cell surface and CD20 on lymphoma cells. Mosunetuzumab-axgb activates T cells and causes the release of proinflammatory cytokines leading to the lysis of B cells. Mosunetuzumab-axgb is indicated in the treatment of adult patients with relapsed/refractory follicular lymphoma (R/R FL) after two or more lines of therapy. This accelerated approval is contingent upon follow-up response rates and was based on results of a Phase II study in R/R FL patients who had received two or more lines of therapy, including at least an anti-CD20 antibody and an alkylating agent (Lancet Oncol 2022; https://doi.org/10.1016/S1470-2045(22)00335-7). Sixty-nine percent were refractory to last treatment and 79 percent were refractory to prior anti-CD20 therapy. Patients received IV treatment in a step-up dosing fashion on a 21-day cycle (see Table) with the primary endpoint being independent review committee-assessed complete response (as best response) rate. Ninety patients were evaluated with a median follow-up of 18.5 months. A decrease in tumor was seen in 95 percent of patients with 80 percent (72 patients) having an objective response and 60 percent (54 patients) achieving a complete response (CR). Duration of response was a median of 22.8 months. The most common adverse event was cytokine release syndrome (CRS, 44%). Grade 3/4 neutropenia, hypophosphatemia, and hyperglycemia were observed. How do you administer this drug? Mosunetuzumab-axgb is administered as an IV injection on a 21-day cycle with step-up dosing for Cycle 1 (see Table). Patients may receive up to 8 cycles (if achieving a CR) or 17 cycles (if achieving a partial response or having stable disease). Therapy should be discontinued for unacceptable toxicity or disease progression. - Day of Treatment Dose Rate of Infusion Cycle 1 Day 1 1 mg Day 8 2 mg Administer over 4 hours minimum Day 15 60 mg Cycle 2 Day 1 60 mg Administer over 2 hours if infusions for Cycle 1 were well-tolerated Cycle 3 and beyond Day 1 30 mg Are there any premedications needed? Premedications are required for Cycle 1 and Cycle 2 with a corticosteroid, acetaminophen, and antihistamine given at least 30-60 minutes prior to the dose. For Cycle 3 and beyond, it is required to give premedications for patients who experience any grade CRS with a previous dose. See package insert for complete drug and dosing recommendations based on the dose the patient is to receive. What are the side effects (>or =10%)? Central nervous system: headache, peripheral neuropathy, dizziness, insomnia General: fatigue, edema, chills, pyrexia GI: diarrhea, abdominal pain, nausea Dermatologic: skin rash, pruritus, dry skin, skin exfoliation Hematologic: cytopenias, hyperglycemia, elevated LFTs, uric acid, hypomagnesemia, hypokalemia, hypophosphatemia Immune system disorders: CRS Neuromuscular/Skeletal: myalgia, arthralgia Respiratory: cough, dyspnea CRS occurred in 44 percent of patients with the majority being Grade 1 (26%) and Grade 2 (17%). Most CRS occurred after Cycle 1 Day 1 (15%), Cycle 1 Day 8 (5%), Cycle 1 Day 15 (33%), and Cycle 2 Day 1 (5%). Only 1 percent of patients experienced CRS in subsequent cycles. Additional side effects include pneumonia, sepsis, COVID-19, EBV viremia, mental status changes (i.e., confusional state, delirium, disturbance in attention, sedation, encephalopathy), tumor lysis syndrome, and ICANS (1%). Are there any important drug interactions? Due to release of cytokines, CYP450 enzyme activity may be suppressed, increasing exposure to CYP450 substrates. Closer monitoring for 14 days after Cycle 2 Day 1, as well as during CRS, may be warranted. How do I adjust the dose in the setting of renal or hepatic insufficiency? There are no dose adjustments for mild-to-moderate renal dysfunction or mild hepatic dysfunction. It has not been studied in severe (CrCl 15-29 mL/min) renal impairment or moderate-to-severe hepatic impairment (total bilirubin >1.5 times upper limit of normal with any AST). Practical tips Do not administer to a patient with an active infection. If CRS or ICANS develop, immediately evaluate for hospitalization. Ensure symptoms have improved to a Grade 1 or baseline for at least 72 hours prior to next dose. All toxicity should resolve prior to the patient driving or operating heavy machinery. Tumor flare has been reported after administration. Patients with bulky tumor or disease located close to airways or vital organs should be monitored closely during initial therapy. Patients should contact their health care provider if they experience fever 100.4F or higher, low blood pressure, fast heartbeat, difficulty breathing, new confusion, headache, or anxiety. Median time to onset of CRS after Cycle 1 Day 1 was 5 hours and ~22 hours for other doses in Cycle 1. What useful links are available for this drug? FDA Accelerated Approval: https://tinyurl.com/3y9buy9f Prescribing Information: https://tinyurl.com/4rzaynyk Are there any ongoing trials? Clinical trials are investigating therapy for R/R FL. Additional trials are reviewing combination with other drugs as maintenance therapy after autologous stem cell transplant and in other diseases. More is available at https://clinicaltrials.gov/. KENDALL SHULTES, PHARMD, BCOP, is Clinical Pharmacy Practitioner in the Stem Cell Transplant & Cellular Therapy in the Department of Veterans Affairs at the Tennessee Valley Healthcare System in Nashville. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, is Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine. He serves as the Pharmacy Forum column physician advisor.Kendall Shultes, PharmD, BCOP: Kendall Shultes, PharmD, BCOPJanelle E. Mann, PharmD, BCOP: Janelle E. Mann, PharmD, BCOPRamaswamy Govindan, MD: Ramaswamy Govindan, MD