Patient and Caregiver Site

Dosage modifications for adverse reactions1

Dose modifications for cytokine release syndrome

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold LUNSUMIO™ until CRS resolves, manage according to the recommendations in this table and per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS.

Recommendations for management of cytokine release syndrome1
Grade* Presenting Symptoms Actions†

Grade 1

 Fever ≥100.4 °F (38 °C)‡
  • Withhold current infusion of LUNSUMIO and manage per current practice guidelines
    • If symptoms resolve, restart infusion at the same rate
  • Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose of LUNSUMIO§
  • Administer premedication|| prior to next dose of LUNSUMIO and monitor patient more frequently

Grade 2

Fever ≥100.4 °F (38 °C)‡ with:

  • Hypotension not requiring vasopressors 

and/or

  • hypoxia requiring low-flow oxygen by nasal cannula or blow-by
  • Withhold current infusion of LUNSUMIO and manage per current practice guidelines
    • If symptoms resolve, restart infusion at 50% rate
  • Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose of LUNSUMIO§
  • Administer premedication|| prior to next dose of LUNSUMIO and consider infusing the next dose at 50% rate
  • For the next dose of LUNSUMIO, monitor more frequently and consider hospitalization

Recurrent Grade 2 CRS

  • Manage per Grade 3 CRS

Grade 3

Fever ≥100.4 °F (38 °C)‡ with:

  • Hypotension requiring a vasopressor (with or without vasopressin)

and/or

  • hypoxia requiring high flow oxygen by nasal cannula, face mask, non-rebreather mask, or Venturi mask
  • Withhold LUNSUMIO, manage per current practice guidelines and provide supportive therapy, which may include intensive care
  • Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose of LUNSUMIO§
  • Administer premedication|| prior to next dose of LUNSUMIO and infuse the next dose at 50% rate
  • Hospitalize for the next dose of LUNSUMIO

Recurrent Grade 3 CRS

  • Permanently discontinue LUNSUMIO
  • Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care

Grade 4

Fever ≥100.4 °F (38 °C)‡ with:

  • Hypotension requiring multiple vasopressors (excluding vasopressin)

and/or

  • hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation and mechanical ventilation)
  • Permanently discontinue LUNSUMIO
  • Manage CRS per current practice guidelines and provide supportive therapy, which may include intensive care

*Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS.
†If CRS is refractory to management, consider other causes including hemophagocytic lymphohistiocytosis.
‡Premedication may mask fever; therefore, if clinical presentation is consistent with CRS, follow these management guidelines.
§Refer to the Dose Delay table for information on restarting LUNSUMIO after dose delays.
‖Refer to the Recommended Premedications table for additional information on premedication.
Low-flow oxygen defined as oxygen delivered at <6 L/minute; high-flow oxygen defined as oxygen delivered at ≥6 L/minute.

Dose modifications for other adverse reactions

Recommendations for management of neurologic toxicity (including ICANS)1
Adverse Reaction Severity*† Actions
Neurologic Toxicity* (Including ICANS†) Grade 2
  • Withhold LUNSUMIO until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours‡
  • Provide supportive therapy. If ICANS, manage per current practice guidelines
Grade 3
  • Withhold LUNSUMIO until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours‡
  • Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines
  • If recurrence, permanently discontinue LUNSUMIO
Grade 4
  • Permanently discontinue LUNSUMIO
  • Provide supportive therapy, which may include intensive care, and consider neurology evaluation. If ICANS, manage per current practice guidelines

Recommended dosage modification for other adverse reactions

For Infections*

  • Grade 1-4: Withhold LUNSUMIO in patients with active infection until the infection resolves‡
  • Grade 4: Consider permanent discontinuation of LUNSUMIO

For Neutropenia*

  • Absolute neutrophil count less than 0.5 x 109/L: Withhold LUNSUMIO until absolute neutrophil count is 0.5 x 109/L or higher‡

For Other Adverse Reactions*

  • Grade 3 or higher: Withhold LUNSUMIO until the toxicity resolves to Grade 1 or baseline‡

*Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
†Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS.
‡See the Dose Delay table for recommendations on restarting LUNSUMIO after dose delays.

LUNSUMIO Download Icon

Download the LUNSUMIO CRS Guide

Download
LUNSUMIO Grading Tool Icon

Explore the CRS Grading Tool

Get information on identifying CRS based on clinical presentation.

Explore now
LUNSUMIO Order Materials Icon

Order LUNSUMIO™ materials

Get informational materials sent to your office.

Order now
chat icon

Contact your representative

Interested in more information about LUNSUMIO?

Contact us
NEXT: CRS Grading Tool

ASTCT=American Society for Transplantation and Cellular Therapy; CRS=cytokine release syndrome; ICANS=immune effector cell-associated neurotoxicity syndrome.

Important Safety Information & Indication

Indication

LUNSUMIO (mosunetuzumab-axgb) is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

BOXED WARNING

Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LUNSUMIO. Initiate treatment with the LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Withhold LUNSUMIO until CRS resolves or permanently discontinue based on severity.

Warnings and Precautions

Cytokine Release Syndrome (CRS)

LUNSUMIO can cause CRS, including serious or life-threatening reactions.

CRS occurred in 39% of patients who received LUNSUMIO at the recommended dose in the clinical trial, with Grade 1 CRS occurring in 28%, Grade 2 in 15%, Grade 3 in 2%, and Grade 4 in 0.5% of patients. Recurrent CRS occurred in 11% of patients. Most patients experienced CRS following doses of 1 mg on Cycle 1 Day 1 (15%), 2 mg on Cycle 1 Day 8 (5%), and 60 mg on Cycle 1 Day 15 (33%). Five percent of patients experienced CRS after receiving 60 mg on Cycle 2 Day 1 with 1% of patients experiencing CRS following subsequent doses of LUNSUMIO.

The median time to onset of CRS from the start of administration in Cycle 1 Day 1 was 5 hours (range: 1 hour to 3 days), Cycle 1 Day 8 was 28 hours (range: 5 hours to 3 days), Cycle 1 Day 15 was 25 hours (range: 0.1 hours to 16 days), and Cycle 2 Day 1 was 46 hours (range: 12 hours to 3 days). The median duration of CRS was 3 days (range: 1 to 29 days).

Clinical signs and symptoms of CRS included, but were not limited to, fever, chills, hypotension, tachycardia, hypoxia, and headache. Concurrent neurologic adverse reactions occurred in 6% of patients and included, but were not limited to, headache, confusional state, and anxiety. Initiate therapy according to LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Administer pretreatment medications to reduce the risk of CRS, ensure adequate hydration, and monitor patients following administration of LUNSUMIO accordingly.

At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold or permanently discontinue LUNSUMIO based on severity.

Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Neurologic Toxicity

LUNSUMIO can cause serious neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

Neurologic toxicity occurred in 39% of patients who received LUNSUMIO at the recommended dose in the clinical trial, with Grade 3 neurologic toxicity occurring in 3% of patients. The most frequent neurologic toxicities were headache (21%), peripheral neuropathy (13%), dizziness (11%), and mental status changes (6%, including confusional state, disturbance in attention, cognitive disorder, delirium, encephalopathy, and somnolence). ICANS was reported in 1% of patients (Grade 1: 0.5%, Grade 2: 0.5%) who received LUNSUMIO at the recommended dose in the clinical trial.

Coadministration of LUNSUMIO with other products that cause dizziness or mental status changes may increase the risk of neurologic toxicity.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient, consider neurology evaluation as appropriate, and provide supportive therapy based on severity; withhold or permanently discontinue LUNSUMIO based on severity and follow management recommendations.

Patients who experience neurologic toxicity such as tremors, dizziness, insomnia, severe neurotoxicity, or any other adverse reactions that impair consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Infections

LUNSUMIO can cause serious or fatal infections. Among patients who received LUNSUMIO at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 17%, with Grade 3 or 4 infections in 14%, and fatal infections in 0.9% of patients. The most common Grade 3 or greater infections were pneumonia, sepsis, and upper respiratory tract infection.

Monitor patients for signs and symptoms of infection prior to and during treatment with LUNSUMIO and treat appropriately. LUNSUMIO should not be administered in the presence of active infection. Caution should be exercised when considering the use of LUNSUMIO in patients with a history of recurring or chronic infections (e.g., chronic, active Epstein-Barr Virus), with underlying conditions that may predispose to infections or who have had significant prior immunosuppressive treatment. Administer prophylactic antimicrobials according to guidelines. Withhold LUNSUMIO or consider permanent discontinuation of LUNSUMIO based on severity.

Cytopenias

LUNSUMIO can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. Among patients who received the recommended dosage in the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 38%, decreased hemoglobin in 19%, and decreased platelets in 12% of patients. Grade 4 decreased neutrophils occurred in 19% and decreased platelets in 5% of patients. Febrile neutropenia occurred in 2%.

Monitor complete blood counts throughout treatment. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue LUNSUMIO. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.

Tumor Flare

LUNSUMIO can cause serious or severe tumor flare. Among patients who received LUNSUMIO at the recommended dosage in the clinical trial, tumor flare occurred in 4% of patients. Manifestations included new or worsening pleural effusions, localized pain and swelling at the sites of lymphoma lesions, and tumor inflammation.

Patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored closely during initial therapy. Monitor for signs and symptoms of compression or obstruction due to mass effect secondary to tumor flare. If compression or obstruction develops, institute standard treatment of these complications.

Embryo-Fetal Toxicity

Based on its mechanism of action, LUNSUMIO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating LUNSUMIO. Advise females of reproductive potential to use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.

Most Common Adverse Reactions

The most common (≥20%) adverse reactions were CRS (39%), fatigue (36%), rash (34%), pyrexia (24%), and headache (21%).

The most common Grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count (92%), decreased phosphate (41%), increased glucose (40%), decreased neutrophil count (38%), increased uric acid (15%), decreased white blood cell count (22%), decreased hemoglobin (19%), and decreased platelets (12%).

Drug Interactions

LUNSUMIO causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP450 substrates. Increased exposure of CYP450 substrates is more likely to occur after the first dose of LUNSUMIO on Cycle 1 Day 1 and up to 14 days after the second 60 mg dose on Cycle 2 Day 1 and during and after CRS. Monitor for toxicity or concentrations of drugs that are CYP450 substrates where minimal concentration changes may lead to serious adverse reactions. Consult the concomitant CYP450 substrate drug prescribing information for recommended dosage modification.

Use in Specific Populations

Lactation

There is no information regarding the presence of mosunetuzumab-axgb in human milk, the effect on the breastfed child, or milk production. Because human IgG is present in human milk, and there is potential for mosunetuzumab-axgb absorption leading to B-cell depletion, advise women not to breastfeed during treatment with LUNSUMIO for 3 months after the last dose.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see the LUNSUMIO full Prescribing Information for additional Important Safety Information, including BOXED WARNING.

    • LUNSUMIO. Prescribing Information. Genentech, Inc.

      LUNSUMIO. Prescribing Information. Genentech, Inc.

    • FDA grants Breakthrough Therapy Designation for Roche’s CD20xCD3 bispecific cancer immunotherapy mosunetuzumab recognising its potential in follicular lymphoma. News release. July 14, 2020. Accessed December 17, 2021.
      https://www.roche.com/investors/updates/inv-update-2020-07-14b.htm.

      FDA grants Breakthrough Therapy Designation for Roche’s CD20xCD3 bispecific cancer immunotherapy mosunetuzumab recognising its potential in follicular lymphoma. News release. July 14, 2020. Accessed December 17, 2021.
      https://www.roche.com/investors/updates/inv-update-2020-07-14b.htm.

    • Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. Published online July 5, 2022. doi:10.1016/S1470-2045(22)00335-7.

      Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. Published online July 5, 2022. doi:10.1016/S1470-2045(22)00335-7.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 26, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Sun LL, Ellerman D, Mathieu M, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7(287):287ra70. doi:10.1126/scitranslmed.aaa4802.

      Sun LL, Ellerman D, Mathieu M, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7(287):287ra70. doi:10.1126/scitranslmed.aaa4802.

    • Ferl GZ, Reyes A, Sun LL, et al. A preclinical population pharmacokinetic model for anti-CD20/CD3 T-cell-dependent bispecific antibodies. Clin Transl Sci. 2018;11(3):296-304. doi:10.1111/cts.12535.

      Ferl GZ, Reyes A, Sun LL, et al. A preclinical population pharmacokinetic model for anti-CD20/CD3 T-cell-dependent bispecific antibodies. Clin Transl Sci. 2018;11(3):296-304. doi:10.1111/cts.12535.

    • BLA Multi-disciplinary Review and Evaluation {BLA 761263, Lunsumio (Mosunetuzumab)}. US Food and Drug Administration. January 2020. Accessed May 14, 2024. https://www.accessdata.fda.gov​/drugsatfda_docs​/nda​/2023​/761263Orig1s000MultidisciplineR.pdf.

      BLA Multi-disciplinary Review and Evaluation {BLA 761263, Lunsumio (Mosunetuzumab)}. US Food and Drug Administration. January 2020. Accessed May 14, 2024. https://www.accessdata.fda.gov​/drugsatfda_docs​/nda​/2023​/761263Orig1s000MultidisciplineR.pdf.

    • Schuster SJ, Sehn LH, Bartlett NL, et al. Mosunetuzumab monotherapy continues to demonstrate durable responses in patients with relapsed and/or refractory follicular lymphoma after ≥2 prior therapies: 3-year follow-up from a pivotal Phase II study. Presented at: The 65th American Society of Hematology Annual Meeting. December 9-12, 2023. Oral presentation.

      Schuster SJ, Sehn LH, Bartlett NL, et al. Mosunetuzumab monotherapy continues to demonstrate durable responses in patients with relapsed and/or refractory follicular lymphoma after ≥2 prior therapies: 3-year follow-up from a pivotal Phase II study. Presented at: The 65th American Society of Hematology Annual Meeting. December 9-12, 2023. Oral presentation.