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August

Tafasitamab-cxix (Monjuvi®) for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Written By: Jeff Engle, PharmD, MS, M Health Fairview University of Minnesota Medical Center

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The purpose of this PQI is to discuss the clinical considerations around the use of tafasitamab-cxix (Monjuvi®) to optimize the outcomes for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Background: DLBCL is an aggressive lymphoma and is the most common subtype of non-Hodgkin’s lymphoma (NHL) in the United States, accounting for approximately 22% of newly diagnosed B-cell NHL cases each year.1 The prognosis for patients with R/R disease remains poor, with expected survival of less than 8 months.2 Tafasitamab-cxix is a CD19-directed cytolytic antibody indicated in combination with lenalidomide for the treatment of adult patients with R/R DLBCL who are not eligible for autologous stem cell transplant (ASCT).3 It was approved in July 2020 under the FDA accelerated approval pathway based on overall response rate and confirmatory trials are currently underway.

Efficacy of this regimen was based on the L-MIND study which was a multicenter, open-label, single arm, phase 2 study enrolling adult patients with R/R DLBCL after 1-3 prior systemic therapies, one of which being an anti-CD20 therapy.4 Patients were not candidates for high dose chemotherapy followed by ASCT. Tafasitamab-cxix was dosed at 12 mg/kg on days 1, 4, 8, 15, 22 for cycle 1; days 1, 8, 15, 22 for cycle 2 and 3; and days 1 and 15 for cycle 4 and beyond. Lenalidomide was dosed at 25 mg daily on days 1-21 of each 28-day cycle for up to 12 cycles. In patients with stable disease or better after 12 cycles, tafasitamab-cxix was administered as monotherapy until disease progression or unacceptable toxicity. The primary endpoint of the study was objective response rate (ORR) with key secondary endpoints being duration of response, progression-free survival (PFS), and overall survival (OS).

At a median follow-up of 13.2 months, 48 of the 80 enrolled patients (60%, 95% CI 48-71%) had an objective response with 34 patients (43%) achieving a complete response. An additional 11 patients (14%) had stable disease which equates to a disease control rate of 74%. The most common grade 3 or worse adverse events were neutropenia (48%), thrombocytopenia (17%), and febrile neutropenia (12%).

A large phase 2-3 randomized trial, B-MIND, is underway to compare tafasitamab-cxix plus lenalidomide versus rituximab plus bendamustine in patients with R/R DLBCL.6

PQI Process: Upon the receipt of a new prescription of tafasitamab-cxix for R/R DLBCL:

  • Review treatment plan:
    • Verify pre-medications: acetaminophen, an H1 receptor antagonist, an H2 receptor antagonist, and a corticosteroid should be given 30-120 minutes prior to the first 3 infusions. If no reaction occurs during the first 3 infusions, then pre-medications are optional with subsequent infusions.
    • Verify tafasitamab-cxix dosing:
      • Cycle 1: 12 mg/kg on days 1, 4, 8, 15, 22
      • Cycles 2-3: 12 mg/kg on days 1, 8, 15, 22
      • Cycle 4+: 12 mg/kg on days 1 and 15
    • Verify lenalidomide dosing: 25 mg once daily on days 1-21 of a 28-day cycle for up to 12 cycles
      • Ensure all lenalidomide REMS requirements are met
      • Dose adjustments needed for baseline renal dysfunction
  • Monitoring:
    • CBC and CMP: baseline and prior to each treatment cycle
    • Consider granulocyte colony-stimulating factor administration in patients who develop neutropenia
  • Preparation:
    • Tafasitamab-cxix are supplied as 200 mg vials
    • Reconstitute each 200 mg tafasitamab-cxix vial with 5 mL of sterile water for injection for a final concentration of 40 mg/mL
    • Dilute the desired volume of tafasitamab-cxix with 250 mL of 0.9% sodium chloride to a final concentration of 2-8 mg/mL
    • Store the diluted tafasitamab-cxix solution refrigerated for up to 18 hours followed by up to 12 hours at room temperature or at room temperature for up to 12 hours. Protect from light during storage
  • Administration:
    • First infusion: administer intravenously at 70 mL/h for the first 30 minutes then increase the rate so that the infusion is administered over 1.5-2.5 hours
    • Subsequent infusions: administer over 1.5-2 hours
    • No incompatibilities have been observed with infusion containers/sets made of polypropylene (PP), polyvinylchloride (PVC), polyethylene (PE), polyethylenterephthalate (PET), or glass
    • Do not co-administer other medications through the same infusion line as tafasitamab-cxix
  • Adverse Event Management: see supplement section

Patient Centered Activities:

  • Patient Education:
    • Review the most common adverse effects: neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite
    • Instruct patient to report any adverse events to the care team
  • My MISSION Support Program
    • Provides support for better understanding health insurance coverage, copay assistance, and free medication for eligible patients
    • Provides treatment calendars and other patient resources for better understanding tafasitamab-cxix

Supplemental Information:

  • Adverse Effect Management
Adverse reactionSeverity

Dosage modification

Hematologic toxicityPlatelets ≤ 50,000/mm3Withhold tafasitamab-cxix (and lenalidomide) and monitor CBC weekly until platelet count is ≥50,000/mm3, then resume tafasitamab-cxix at the same dose (and lenalidomide at a reduced dose according to prescribing information).
Neutrophil count ≤ 1,000/uL for at least 7 days or neutrophil count ≤ 1,000 with fever (temp ≥100.4°F or ≥38°C) or neutrophil count < 500/uL
Infusion-related reactionGrade 2 (moderate)Interrupt infusion immediately and manage signs/symptoms. Once signs/symptoms resolve or reduce to grade 1, resume infusion at no more than 50% of the rate at which the reaction occurred. If no further reaction within 1 hour and vital signs are stable, may increase infusion rate every 30 minutes as tolerated to rate at which the reaction occurred.
Grade 3 (severe)Interrupt infusion immediately and manage signs/symptoms. Once signs/symptoms resolve or reduce to grade 1, resume infusion at no more than 25% of the rate at which the reaction occurred. If no further reaction within 1 hour and vital signs are stable, may increase infusion rate every 30 minutes as tolerated to a maximum of 50% of the rate at which the reaction occurred. Stop infusion immediately if reaction returns upon rechallenge.
Grade 4 (life threatening)Stop infusion immediately and permanently discontinue tafasitamab-cxix.

 

References:

  1. Lymphoma Research Foundation. Understanding diffuse large B-cell lymphoma. 2020; Available at: https://lymphoma.org/wp-Content/uploads/2018/05/LRF_FACTSHEET_DIFFUSE_LRG_BCELL_LYMPHOMA_DLBCL.pdf. Accessed May 27, 2021.
  2. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808.
  3. Monjuvi (tafasitamab) [prescribing information]. Boston, MA: Morphosys US Inc.; 2020.
  4. Salles G, Duell J, Gonzalez Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988.
  5. Nowakowski G, Rodgers TD, Marino D, et al. RE-MIND study: a propensity score-based 1:1-matched comparison of tafasitamab + lenalidomide (L-MIND) versus lenalidomide monotherapy (real-world data) in transplant-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(Supplement_15): 8020 and Poster 353.
  6. Nowakowski GS, Belada D, Molina L, et al. B-MIND: MOR208 plus bendamustine (BEN) versus rituximab (RTX) plus BEN in patients with relapsed or refractory (R-R) diffuse large B-cell lymphoma (DLBCL): an open-label, randomized phase II/III trial. J Clin Oncol. 2017;35(Supplement_15):TPS7571.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
Katie Edmiston

Katie Edmiston has blogged 140 posts

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