Example orders for Rituximab (Rituxan) desensitization protocol

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02998528

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Rituximab (Rituxan) desensitization protocol

Original references may be found at Rituximab (Rituxan) desensitization protocol

Example regimen #1

• Solution #1 of Rituximab (Rituxan) 3.75 mg/m² (in 250 mL NS) IV, given at the following rates & durations
  • Step 1: 2 mL/H x 15 minutes (0.5 mL volume)
  • Step 2: 5 mL/H x 15 minutes (1.25 mL volume)
  • Step 3: 10 mL/H x 15 minutes (2.5 mL volume)
  • Step 4: 20 mL/H x 15 minutes (5 mL volume)
• Solution #2 of Rituximab (Rituxan) 37.5 mg/m² (in 250 mL NS) IV, given at the following rates & durations
  • Step 5: 5 mL/H x 15 minutes (1.25 mL volume)
  • Step 6: 10 mL/H x 15 minutes (2.5 mL volume)
  • Step 7: 20 mL/H x 15 minutes (5 mL volume)
  • Step 8: 40 mL/H x 15 minutes (10 mL volume)
• Solution #3 of Rituximab (Rituxan) 375 mg/m² (in 250 mL NS) IV, given at the following rates & durations
  • Step 9: 10 mL/H x 15 minutes (2.5 mL volume)
  • Step 10: 20 mL/H x 15 minutes (5 mL volume)
  • Step 11: 40 mL/H x 15 minutes (10 mL volume)
  • Step 12: 80 mL/H x 172.9 minutes (230.5 mL volume)
• Patient received Bendamustine 90 mg/m² IV over 30 minutes (Treanda formulation) x 2 days as an outpatient as part of the BR regimen for follicular lymphoma

28-day cycles

Supportive medications

• Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to the start of rituximab
• Famotidine (Pepcid) 20 mg IV over 15 minutes, 30 minutes prior to the start of rituximab
• Lorazepam (Ativan) 0.5 IV Q6H prn anxiety
• Montelukast (Singulair) 10 mg PO 12 hours prior to the start of rituximab
• Hydrocortisone (Cortef) 25 mg IV 30 minutes prior to the start of rituximab
• Diphenhydramine (Benadryl) 25-50 mg PO/IV prn allergic reaction
  • If the patient develops a mild reaction, such as fever, self-limiting rash, itching, mild chest tightness, abdominal or back pain, nausea, another dose of Diphenhydramine (Benadryl) 25-50 mg PO/IV may be given. Observe until the reaction improves, then resume the infusion at the point where it was stopped. If the reaction does not improve within 30 minutes, contact the allergist on call.
• Epinephrine (Epipen) 0.3 mg IM prn allergic reaction
  • If the patient develops a moderate to severe reaction, such as acute dyspnea or angioedema, and/or acute hypotension, stop protocol, follow ACLS guidelines to treat, use Epinephrine (Epipen) 0.3 mg IM for hypotension or glottic edema, and nebulized albuterol for bronchospasm. Discuss the event with the attending allergy physician on call. When the patient is stable, the protocol may be resumed (with allergist's guidance regarding the rate at which to restart and with revisions if necessary).

Hydration:

• 500 ml NS at KVO rate as running IV for chemotherapy infusion. Give up to 500 ml NS.

Clinical scenario & comments:
This is my institution's standard Rituximab (Rituxan) desensitization protocol. The patient was a 66 year-old gentleman with low grade, stage IV follicular lymphoma and large abdominal mass causing lymphatic obstruction, with chylothorax and ascites. Previously received cycle 1 day 1 of R-Bendamustine, with infusion reaction during Rituximab (Rituxan) characterized by rigors, dyspnea, hypertension, tachycardia, diffuse pulmonary wheezes. Rituximab was stopped, and his symptoms improved with furosemide (Lasix), meperidine (Demerol), and metoprolol (Lopressor). There was concern for allergic reaction, so he was transferred to the ICU for rituximab desensitization, premedicated with hydrocortisone, Diphenhydramine (Benadryl), Montelukast (Singulair), and Famotidine (Pepcid), and tolerated it well. He had a significant decrease in disease burden, and was admitted to have an additional dose of rituximab at cycle 1 day 18 in an effort to accelerate his symptomatic improvement. Since hydrocortisone was used with the previous desensitization, this was used again. He tolerated this cycle 1 day 18 dose of rituximab well, and was assessed as not truly having a rituximab allergy, but rather an infusion reaction related to his previously high burden of disease. He received his cycle 2 rituximab as an outpatient without desensitization protocol and tolerated it well.