ADULT Updated: September 4, 2018

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Updated: September 4, 2018 Regimen Reference Order ARIA: LYMP [R-CHOP alt. R-DHAP] Planned Course: Indication for Use: Every 21 days for 6 cycles (R-CHOP given on cycles 1, 3 and 5; R-DHAP given on cycles 2, 4 and 6) Mantle Cell Lymphoma, 1 st line (transplant eligible patients) CVAD: At Provider s Discretion (VESICANT INVOLVED) Proceed with treatment if: Cycles 1, 3 and 5 (R-CHOP): ANC equal to or greater than 0.8 x 10 9 /L AND Platelets equal to or greater than 100 x 10 9 /L Cycles 2, 4 and 6 (R-DHAP): ANC equal to or greater than 1 x 10 9 /L AND Platelets equal to or greater than 75 x 10 9 /L Contact Hematologist if parameters not met SEQUENCE OF MEDICATION ADMINISTRATION R-CHOP Pre-treatment Requirements R-CHOP (cycles 1, 3 and 5) prednisone 100 mg Orally once on Days 1 to 5 (Self-administered at home) Cycles 1, 3 and 5 R-CHOP PrednisONE is started Day 1 regardless if R-CHOP is given over one day or split over two days allopurinol* 300 mg Orally once daily for 10 days to begin 3 days prior to Cycle 1 and at provider s discretion for subsequent cycles * Only patients at risk of tumor lysis syndrome will be prescribed allopurinol Treatment Regimen LYMP R-CHOP (cycles 1, 3 and 5) Establish primary solution 500 ml of: normal saline acetaminophen 650 mg Orally 30 minutes prior to rituximab dexamethasone* 12 to 20 mg 20 mg for Cycle 1 IV in normal saline 50 ml over 15 minutes Prior to rituximab diphenhydramine 50 mg IV in normal saline 50 ml over 15 minutes Please refer to CCMB Formulary for Criteria for Use Page 1 of 6

rituximab 375 mg/m 2 Slow infusion (if greater than 6 months since last rituximab dose or no previous rituximab): IV made up to a final concentration of 1 mg/ml in normal saline. Start at 50 mg/hr for 60 minutes and escalate infusion rate in 50 mg/hr increments every 30 minutes to maximum of 400 mg/hr *Nursing Alert: IV tubing is primed with rituximab Slow infusion (if equal to or less than 6 months since last rituximab dose): IV made up to a final concentration of 1 mg/ml in normal saline. Start at 100 mg/hr for 30 minutes and escalate infusion rate in 100 mg/hr increments every 30 minutes to maximum of 400 mg/hr *Nursing Alert: IV tubing is primed with rituximab Cycle 3 and 5 Rapid infusion: IV in normal saline over 90 minutes: Infuse 50 ml of a 250 ml bag (or 100 ml of a 500 ml bag) over 30 minutes, then infuse the remaining 200 ml (or 400 ml of a 500 ml bag) over 60 minutes Concentration dependent drug. Pharmacy will adjust diluent volume to ensure drug stability 1400 mg (1400 mg = 11.7 ml) Cycle 3 and 5 Subcutaneous: Subcutaneous administered over 5 minutes into abdomen Syringe should be held in hand for 5 minutes to warm up and decrease viscosity Use 25G needle *Nursing Alert: Ensure subcutaneous rituximab formulation is used ondansetron 16 mg Orally 30 minutes pre-chemotherapy DOXOrubicin 50 mg/m 2 IV Push over 10 to 15 minutes vincristine 1.4 mg/m 2 ; maximum dose 2 mg IV in normal saline 25 ml over 2 to 3 minutes cyclophosphamide 750 mg/m 2 IV in normal saline 250 ml over 1 hour *If R-CHOP is split over two days, give dexamethasone prior to CHOP All doses will be automatically rounded that fall within the DSG Approved Dose Bands. See LYMP DSG Dose Banding document for more information Flush after each medication: 50 ml over 6 minutes (500 ml/hr) In the event of an infusion-related hypersensitivity reaction, refer to the Hypersensitivity Reaction Standing Order Please refer to CCMB Formulary for Criteria for Use Page 2 of 6

REQUIRED MONITING R-CHOP Day 1 CBC, biochemistry as per physician order Left Ventricular Ejection Fraction (LVEF) monitoring is recommended at baseline and as clinically indicated INTRAVENOUS route Full vital signs (temperature, heart rate, blood pressure, respiration and O 2 saturation) prior to each dose of rituximab and as clinically indicated No observation period is required Patient can be discharged from treatment room if stable whether they had a reaction or not SUBCUTANEOUS route Full vital signs (temperature, heart rate, blood pressure, respiration and O 2 saturation) prior to dose, at discharge, and as clinically indicated 15 minute observation period required after each dose Recommended Support Medications R-CHOP ondansetron 8 mg Orally every 12 hours for 2 doses starting the evening of chemotherapy and then every 12 hours as needed thereafter metoclopramide 10 20 mg Orally every 4 6 hours as needed for nausea and vomiting DISCHARGE INSTRUCTIONS R-CHOP Instruct patient to: o Continue taking anti-emetic(s) at home o Maintain oral intake of 2000 ml (8 glasses) of fluid daily at home o Empty bladder every 2 hours while awake and at bedtime for 24 hours o Obtain immediate assistance as per your clinic s contact instructions if: Signs of hemorrhagic cystitis Unable to drink recommended amount of fluid Patients should be instructed to contact their cancer team immediately if symptoms of hypersensitivity reactions occur after discharge Remind patient to take prednisone at home Reinforce applicable safe handling precautions of medications, blood and body fluids for 48 hours after completion of chemotherapy ADDITIONAL INFMATION R-CHOP Administering nurse must document any infusion related-reactions with any dose of rituximab Ensure there were no Grade 3 or 4 infusion-related reaction with the previous dose prior to administering rituximab via Rapid Infusion or Subcutaneous injection rituximab Rapid Infusion or Subcutaneous injection not to be given on Cycle 1 Please refer to CCMB Formulary for Criteria for Use Page 3 of 6

Pre-treatment Requirements R-DHAP (cycles 2, 4 and 6) dexamethasone 40 mg Orally once daily on Days 2, 3 and 4 (Self-administered at home) prednisolone 1% eye drops 2 drops Instill 2 drops into each eye beginning the morning of cytarabine and continue for 48 hours after the last dose of cytarabine Treatment Regimen LYMP R-DHAP (cycles 2, 4 and 6) Establish primary solution 500 ml of: normal saline Day 1 acetaminophen 650 mg Orally 30 minutes prior to rituximab dexamethasone 40 mg IV in normal saline 50 ml over 15 minutes diphenhydramine 50 mg IV in normal saline 50 ml over 15 minutes 2 Slow infusion: IV made up to a final concentration of 1 mg/ml rituximab 375 mg/m in normal saline. Start at 100 mg/hr for 30 minutes and escalate infusion rate in 100 mg/hr increments every 30 minutes to maximum of 400 mg/hr *Nursing Alert: IV tubing is primed with rituximab Rapid infusion: IV in normal saline over 90 minutes: Infuse 50 ml of a 250 ml bag (or 100 ml of a 500 ml bag) over 30 minutes, then infuse the remaining 200 ml (or 400 ml of a 500 ml bag) over 60 minutes Concentration dependent drug. Pharmacy will adjust diluent volume to ensure drug stability 1400 mg (1400 mg = 11.7 ml) Subcutaneous: Subcutaneous administered over 5 minutes into abdomen Syringe should be held in hand for 5 minutes to warm up and decrease viscosity Use 25G needle *Nursing Alert: Ensure subcutaneous rituximab formulation is used Please refer to CCMB Formulary for Criteria for Use Page 4 of 6

Day 2 normal saline 1000 ml IV over 2 hours (Pre Hydration) ondansetron 16 mg Orally 30 minutes pre-chemotherapy 2 IV in normal saline 500 ml over 1 hour CISplatin 100 mg/m Mixed with mannitol mannitol 12.5 mg IV in normal saline 500 ml over 1 hour Mixed with CISplatin normal saline 1000 ml IV over 2 hours (Post Hydration) Days 3 and 4 Establish primary solution 500 ml of: normal saline ondansetron 16 mg Orally 30 minutes pre-chemotherapy cytarabine 2000 mg/m 2 IV in normal saline 500 ml over 3 hours All doses will be automatically rounded that fall within the DSG Approved Dose Bands. See LYMP DSG Dose Banding document for more information Flush after each medication: 50 ml over 6 minutes (500 ml/hr) In the event of an infusion-related hypersensitivity reaction, refer to the Hypersensitivity Reaction Standing Order REQUIRED MONITING R-DHAP Day 1 CBC, serum creatinine, urea, electrolytes, LFTs, LDH, total bilirubin, uric acid, albumin prior to each cycle INTRAVENOUS route Full vital signs (temperature, heart rate, blood pressure, respiration and O 2 saturation) prior to each dose of rituximab and as clinically indicated No observation period is required Patient can be discharged from treatment room if stable whether they had a reaction or not SUBCUTANEOUS route Full vital signs (temperature, heart rate, blood pressure, respiration and O 2 saturation) prior to dose, at discharge, and as clinically indicated 15 minute observation period required after each dose Grastofil Recommended Support Medications R-DHAP 5 mcg/kg (rounded to nearest 300 mcg or 480 mcg) Subcutaneously once daily for 7 days to start on Day 6 ondansetron 8 mg Orally twice daily as needed starting Day 5 for nausea and vomiting aprepitant 125 mg Orally on Day 2 of chemotherapy cycle 80 mg Orally on Days 3 and 4 of chemotherapy cycle metoclopramide 10 20 mg Orally every 4 6 hours as needed for nausea and vomiting Please refer to CCMB Formulary for Criteria for Use Page 5 of 6

DISCHARGE INSTRUCTIONS R-DHAP Instruct patient to continue taking anti-emetic(s) at home Remind patient to take dexamethasone at home cytarabine can cause conjunctivitis. Remind patient to instill prednisolone eye drops until 48 hours after the last dose of cytarabine. If patient continues to have signs and symptoms of conjunctivitis, then please contact prescribing hematologist for further instructions Patients should be instructed to contact their cancer team immediately if symptoms of hypersensitivity reactions occur after discharge Reinforce applicable safe handling precautions of medications, blood and body fluids for 48 hours after completion of chemotherapy ADDITIONAL INFMATION R-DHAP Administering nurse must document any infusion-related reactions with any dose of rituximab Ensure there were no Grade 3 or 4 infusion-related reaction with the previous dose prior to administering rituximab via Rapid Infusion or Subcutaneous injection CISplatin is ototoxic and nephrotoxic cytarabine can cause mental confusion Please refer to CCMB Formulary for Criteria for Use Page 6 of 6