What is tafasitamab?
Tafasitamab is a cytolytic monoclonal antibody that is directed at CD19-positive pre-B and mature B lymphocytes.
It binds to CD19 surface antigens expressed on pre-B and mature B lymphocytes. After binding occurs, tafasitamab facilitates B-cell lysis by apoptosis, including antibody-dependent cellular toxicity and phagocytosis.
What is this approved for?
Tafasitamab is approved in combination with lenalidomide for autologous stem cell transplant ineligible adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL developing from low-grade lymphoma.
What is the basis for this approval?
Tafasitamab was approved based on the results of the L-MIND trial, a Phase II, multicenter, open-label, single-arm trial in transplant-ineligible patients with relapsed/refractory DLBLC after 1-3 previous regimens with at least one containing an anti-CD20 therapy (Lancet Oncol 2020;21:978-988).
A total of 80 patients received lenalidomide 25 mg by mouth on days 1-21 (28-day cycle) for a maximum of 12 cycles in combination with tafasitamab. Tafasitamab was administered at 12 mg/kg intravenously as follows:
* Cycle 1: Days 1, 4, 8, 15, 22
* Cycle 2 and 3: Days 1, 8, 15, 22
* Cycle 4 and beyond: Days 1, 15
Patients could continue on tafasitamab monotherapy until disease progression or toxicity after completion of a maximum of 12 cycles of lenalidomide combination. The primary endpoint was objective response rate. Sixty percent (48/80) of patients achieved an objective response with 43 percent achieving a complete response (34/80). With a median follow-up of 13.2 months, 30 (37%) of patients completed 12 cycles of combination therapy and 35 percent were receiving monotherapy (Lancet Oncol 2020;21:978-988).
How do you administer this drug?
Tafasitamab is administered intravenously. The first dose starts with an infusion rate of 70 mL/hr for 30 minutes with subsequent rate increases for full administration within 1.5-2.5 hours. Subsequent infusions may be given within 1.5-2 hours.
Are there any premedications needed?
To minimize infusion reactions, acetaminophen, histamine H1/H2 agonists, and/or glucocorticoids should be given at least 30 minutes prior to the infusion. By dose 4, if the patient is not experiencing any infusion-related reactions, premedication becomes optional.
What are common side effects (> or =10%)?
* Hematologic: neutropenia (51%), anemia (36%), thrombocytopenia (31%), febrile neutropenia (12%)
* Fatigue (38%)
* Pyrexia (24%)
* Peripheral edema (24%)
* GI: diarrhea (36%), constipation (17%), nausea/vomiting (15%)
* Cough (26%)
* Dyspnea (12%)
* Infections: respiratory tract infections (24%), urinary (17%), bronchitis (16%)
* Decreased appetite (22%)
* Hypokalemia (19%)
* Back pain (19%)
* Elevated lab values: glucose (49%), GGT (34%), creatinine (20%), AST (20%), aPTT (46%)
* Decreased lab values: calcium (47%), albumin (26%), magnesium (22%), phosphate (20%)
What are uncommon side effects (less than 10%)?
Additional side effects include infusion-related reactions (6%), lymphopenia (6%), sepsis (4.9%), erythema (4.9%), headache (9%), alopecia (2.5%).
Are there drug interactions to be aware of?
There are no known drug interactions with tafasitamab.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no known dose adjustments for patients with renal or hepatic insufficiency. However, tafasitamab has not been studied in patients with CrCl < 30 mL/min or moderate-to-severe hepatic impairment.
Practical Tips
* Tafasitamab reduces peripheral blood B-cell counts by 97 percent within 8 days of treatment and 100 percent by 16 weeks.
* If a patient experiences an infusion reaction, the dose should be interrupted. For mild/moderate reactions, once the symptoms resolve, the infusion can restart at 50 percent of the previous rate for 1 hour and then increased every 30 minutes as tolerated. For severe reactions (grade 3), once resolved, the rate should start at 25 percent of the previous rate for 1 hour and increased every 30 minutes to a maximum of 50 percent of the previous rate.
What should my patients know about tafasitamab?
Patients should contact their health care provider if they experience any of the following: infusion reaction, signs or symptoms of an infection
What else should I know about this drug?
* Elevations in aPTT occurred in 46 percent of patients. The clinical relevance of this is yet to be determined.
* No patients developed anti-tafasitamab antibodies during the clinical trial.
What useful links are available regarding tafasitamab?
* FDA Approval Announcement: https://bit.ly/3mT6DTL
Any clinical trials related to this drug?
Clinical trials with tafasitamab are ongoing in DLBLC in combination with bendamustine or R-CHOP and CLL in combination with idelalisib or venetoclax. Information is available at https://clinicaltrials.gov.
SARA BUTLER, PHARMD, BCOP, BCPS, is Manager of Clinical Pharmacy and Investigational Drug Services at Barnes-Jewish Hospital, Saint Louis, Mo. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/ Manager, Clinical Pharmacy Services at Washington University School of Medicine, Saint Louis, Mo. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.