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.
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.