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The following information helps you to find FDA Alerts and Pharmacist’s Applications to Practice quickly and easily. In cooperation with the Food and Drug Administration (FDA), and as a service to our members, HOPA periodically distributes information about newly approved therapies for cancer patients from FDA’s Office of Oncology Drug Products Director, Dr. Richard Pazdur to inform oncologists and professionals in oncology-related fields in a timely manner. Links to product labels will take you to relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, HOPA does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.

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December 21, 2018, with PAP

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761116s000lbl.pdf.

On December 21, 2018, the Food and Drug Administration approved tagraxofusp-erzs(ELZONRIS™, Stemline Therapeutics), a CD123-directed cytotoxin, for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older.

Approval was based on a multicenter, multicohort, open-label, single-arm clinical trial (STML-401-0114; NCT 02113982) in patients with untreated or relapsed/refractory BPDCN. Patients received tagraxofusp-erzs at the recommended dose of 12 mcg/kg (see schedule below) In the pivotal cohort, seven (53.8%; 95% CI: 25.1, 80.8) of 13 patients with untreated BPDCN achieved complete response/clinical complete response after a median follow-up of 11.5 months. The median response duration was not reached. In the second cohort, of 15 patients with relapsed or refractory BPDCN, one patient achieved a complete response (duration 111 days) and one patient achieved a clinical complete response (duration 424 days).

Most common adverse reactions (incidence ≥ 30%) are capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase. Most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, and sodium, and increases in glucose, ALT and AST.

The recommended tagraxofusp-erzs dose and schedule is 12 mcg/kg administered intravenously over 15 minutes once daily on days 1 to 5 of a 21-day cycle.

View full prescribing information for ELZONRIS.

FDA granted this application priority review and breakthrough therapy designation. This therapy also received orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.


Pharmacist’s Applications to Practice

Tagraxofusp-erzs for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

Authors: Jennifer E. MacDonald, PharmD BCOP
Oncology Clinical Pharmacy Specialist
Medical University of South Carolina
Charleston, SC

Andy Maldonado, PharmD BCOP
Oncology Clinical Pharmacy Specialist
Medical University of South Carolina
Charleston, SC

What is the potential role for tagraxofusp-erzs in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN)?

  • Because of the rarity of BPDCN and the median age of diagnosis in the sixth decade of life, tagraxofusp-erzs is a novel therapy.1,2
    • Median overall survival for these patients is 9–13 months but may be higher in patients who are able to receive an allogeneic stem cell transplant.2
    • Prior to the approval of this agent, conventional chemotherapy with regimens commonly used to treat acute leukemia or aggressive lymphoma was preferred in the frontline setting, with limited application to elderly patients unable to tolerate intensive chemotherapy regimens.1,2
    • Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) historically boasts only a 40%–50% complete response (CR) rate, with short duration of response and frequent relapse.1,2
    • CD123 is highly expressed on precursor dendritic cells, making it an attractive target.1,2
    • In the STML-401-0114 trial, tagraxofusp-erzs, a CD123-directed cytotoxin, demonstrated a CR or clinical complete response in 7 of 13 (53.8%) previously untreated patients with BPDCN, with a median response duration not reached.2-5
      • In the relapsed or refractory cohort, 1 of 15 (6.67%) patients achieved a CR, and 1 of 15 (6.67%) achieved a clinical complete response.2,3
  • Tagraxofusp-erzs can be used as a bridge to transplant.3
    • In an expanded group of 29 previously untreated patients who received tagraxofusp-erzs at 12 mcg/kg, 10 patients went on to receive an allogeneic stem-cell transplant, and 3 received an autologous stem-cell transplant.
    • One of 15 patients who had received prior treatment achieved a second complete remission (CR2) on tagraxofusp-erzs and went on to receive an allogeneic stem-cell transplant.
  • Tagraxofusp-erzs could change the landscape of the treatment of BPDCN when it is used as upfront therapy followed by subsequent bone marrow transplant. It offers a potential for cure as well as significant improvement in overall survival rates in this rare and difficult-to-treat malignancy.

What role can the pharmacist play in the management of patients on tagraxofusp-erzs?

  • Patients on tagraxofusp-erzs should be monitored closely for the development of capillary leak syndrome (CLS).3-5
    • In the clinical trial, CLS was reported in 8 of 44 (18%) patients who received the 12 mcg/kg dose. 
    • Two of the 8 patients died, and another patient who received the 7 mcg/kg dose also died.
    • The median onset to the development of CLS was 5 days and lasted for approximately 4 days (range: 3-19 days). All but one of the cases of CLS occurred during the first cycle.
    • The drug manufacturer recommends administering the first cycle of tagraxofusp-erzs in the inpatient setting and monitoring patients for a minimum of 24 hours after the last infusion. 
    • If the patient tolerates the first cycle well, then future cycles may be administered in the outpatient setting with appropriate observation and monitoring following each dose.
    • Decreased serum albumin during the initial treatment days was noted to contribute to the development of CLS. Serum albumin and patient weight should be monitored prior to each dose of tagraxofusp-erzs.
    • Patients who developed CLS were managed by delaying or withholding additional tagraxofusp-erzs doses as well as administering albumin (see package insert for CLS management guidelines).
  • Monitor for signs and symptoms of hypersensitivity reactions, including rash, pruritis, stomatitis, and wheezing.4,5
  • Additional side effects include increased liver enzymes, hypoalbuminemia, peripheral edema, and thrombocytopenia.3-5
  • Pharmacists can help educate nursing and pharmacy technician staff regarding some unique aspects in the preparation of tagraxofusp-erzs, such as use of a syringe pump, inline filter, and mini-bifuse Y-connector.
  • Helpful videos on the preparation and administration of tagraxofusp-erzs can be found on the Elzonris website: www.elzonris.com/hcp/dosing-administration.
  • Pharmacists can play a role in referring patients for financial assistance via the Stemline ARC program, available at https://elzonris.com/hcp/stemline-arc-summary/.

Clinical Pearls

  • Tagraxofusp-erzs is the first FDA-approved agent for the treatment of BPDCN.
  • The recommended dose of tagraxofusp-erzs is 12 mcg/kg administered as an intravenous infusion over 15 minutes on days 1–5 of every 21-day cycle.4,5
  • Doses may be delayed up to day 10 of each cycle for management of toxicities.3-5
  • Ensure that patients have adequate cardiac function and a serum albumin of at least 3.2 g/dL prior to initiating therapy.4,5
  • Patients should be premedicated with acetaminophen, an H1-antagonist (e.g., diphenhydramine), an H2-antagonist (e.g., ranitidine), and a corticosteroid (e.g., 50 mg IV methylprednisolone or an equivalent) approximately 60 minutes prior to each dose of tagraxofusp-erzs.4,5
  • CLS was a severe adverse effect seen in the pivotal study, and patients should be monitored closely for signs and symptoms of CLS, including weight gain and hypoalbuminemia.

References

  1. Sullivan JM, Rizzieri DA. Treatment of blastic plasmacytoid dendritic cell neoplasm. Hematology Am Soc Hematol Educ Program. 2016; 2016(1):16-23.
  2. Laribi K, Denizon N, Besancon A, et al. Blastic plasmacytoid dendritic cell neoplasm: from origin of the cell to targeted therapies. Biol Blood Marrow Transplant. 2016; 22(8):1357-1367.
  3. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med. 2019; 380:1628-1637.
  4. Elzonri (tagraxofusp-erzs) for injection [package insert]. New York, NY: Stemline Therapeutics; December 2018. 
  5. Lexicomp Online, Lexi-Drugs Online. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc.; May 23, 2019.
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