Written by: Jody Agena, PharmD, Virginia Cancer Specialists
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Description: Understand how to identify eligible patients and manage adverse effects of regorafenib treatment in hepatocellular carcinoma.

Background: Regorafenib is a kinase inhibitor indicated for the treatment of patients (Childs Pugh A) with Hepatocellular Carcinoma (HCC) who have been previously treated with sorafenib.  In the phase III – RESORCE Trial, regorafenib was assessed in patients with HCC who have progressed on sorafenib and concluded that there was an improved overall survival compared to placebo (10.6 months vs. 7.8 months). This study also portrayed the difficulties of maintaining therapy, as the discontinuation rate due to adverse events within the treatment arm was observed at 25% and 43% due to progression. The most common grade (all grade) adverse events occurring more frequently in the regorafenib group included:  Hand-foot skin reaction (51%), asthenia/ fatigue (42%), diarrhea (41%), and hypertension (31%). In addition to regorafenib, other 2nd line options include nivolumab.  Patients that are not eligible for nivolumab may include those with comorbidities including but not limited to: pneumonitis, thyroid disorders, renal dysfunction, colitis, previous transplants.

PQI Process: Consider reviewing all current HCC patient in EMR for appropriateness of regorafenib therapy
Upon receipt of a new prescription for Regorafenib:

  • If the typical starting dose of 160 mg by mouth once a day is written, consider initiating dose titration based on the mCRC ReDos trial in metastatic colorectal cancer (mCRC)
    • Initiate patient at 80 mg for the first week of cycle 1
    • If no significant drug-related toxicities, escalate to 120 mg for the second week of cycle 1, otherwise hold therapy at current dose
    • If no significant drug-related toxicities, escalate to 160 mg for the third week of cycle 1, otherwise hold therapy at current dose
    • For following cycles, start therapy at current tolerated dose (no dose escalation)
  • Coordinate and establish a weekly follow up call with the patient or caregiver for the first 8 weeks
  • Monitor baseline LFTs
  • CBC with differential and platelets and serum electrolytes at baseline and monthly
  • Monitor blood pressure weekly for the first 6 weeks of therapy, then every cycle
  • Monitor for hand-foot skin reaction (HFSR) weekly for 2 cycles, then every cycle
  • Monitor for signs/symptoms of cardiac issues, bleeding, GI perforation or fistula, infection, and/or neurological symptoms
  • Monitor for impaired wound healing – Hold medication for 2 weeks prior to surgery to allow proper wound healing
  • Consider providing urea base moisturizer
  • Consider use of anti-diarrheals

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) Sheet
    • Emphasize counseling on side effect table
    • Educate patients on side effects and report adverse effects to prescriber and recommend dose adjustments in 40 mg increments as tolerated
    • Dosing is once daily for 3 weeks on therapy then 1 week off therapy per cycle
    • Medication expires 7 weeks after opening bottle
      • Packaging now available in 21 count bottle
    • Take dosage with low fat meal (< 600 calories)
      • Examples of Low Fat food choices5
        • Dairy and dairy-like products
          • Low-fat (1%) or fat-free (skim) yogurt, cottage cheese, or milk
          • Fat-free American cheese or other types of fat-free cheeses
        • Fish, meat, poultry, and other protein
          • Egg whites or egg substitutes
          • Crab, white fish, shrimp, and light tuna (packed in water)
          • Chicken and turkey breast (without skin), or ground turkey breast
          • Beans, peas, and lentils, cooked (or canned) without added fats
        • Grains, cereals, and pastas
          • Hot (oatmeal or grits) and cold cereals (except granola types)
          • Whole grain brown rice or noodles (watch out for fat in added sauces)
          • Whole grain bagels, pita bread, or English muffins
          • Low-fat crackers and breads
          • Soft tortillas – corn or whole wheat
        • Fruits- including fresh, frozen, or canned (in their own juice)
        • Vegetables- including fresh, frozen, or canned (choose lower-sodium varieties)
        • Other foods
          • Broth type soups with a vegetable base
          • Sauces, pudding, or shakes made with skim milk

References:

  1. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Bruix, Jordi et al. The Lancet, Volume 389 , Issue 10064 , 56 – 66.
  2. Ou FS, Bekaii-Saab T. ReDOS* trial presented at the ASCO GI Cancers Symposium 2018. ReDOS poster from ASCO GI, Jan. 2018.
  3. NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines®) for colon cancer v.2.2018. © Page COL-D 9 of 10. National Comprehensive Cancer Network 2018. All rights reserved.
  4. Bekaii-Saab T, Ou FS, Ciombor KK, et al. Regorafenib dose optimization study (ReDOS): A phase II randomized study of lower starting dose regorafenib compared to standard dose regorafenib in patients with refractory metastatic colorectal cancer (mCRC). Journal of Clinical Oncology 2016 34:15_suppl, TPS3630-TPS3630.
  5. STIVARGA® (Regorafenib) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals.
  6. https://www.cancer.org/healthy/eat-healthy-get-active/take-control-your-w.
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.
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Written by: Michelle Phillips, PharmD, University of Rochester Medical Center
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Description: The purpose of this PQI is to highlight key criteria for appropriate monitoring, dosing, and administration to improve the dispensing and management of patients taking niraparib (Zejula).

Background: Niraparib is indicated for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Additional indication in patients with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status (BRCA+ or BRCA- with Genomic Instability Positive (GIS+) disease).  Niraparib efficacy is particularly pronounced in patients with BRCA1/2 mutations but also yields therapeutic benefit in those without germline BRCA mutations.

Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 1%, and 2% of patients. Retrospective analysis of the pivotal phase III NOVA clinical trial reveals most dose adjustments occurred within 3 months and did not appear to compromise efficacy.

PQI Process:

  • Verify dose on initial fill—labeled starting dose is 300 mg once daily
    • Consider starting at 200 mg daily for patients with baseline weight < 77 kg or baseline platelets < 150K.
    • In practice, it has been seen at starting doses of 100 mg once daily as well
  • Ensure patients should start treatment with niraparib no later than 8 weeks after their most recent platinum-containing regimen
  • Consider bevacizumab discontinuation before initiation of treatment with niraparib
  • Ensure appropriate monitoring:
    • CBC weekly x 4 weeks, monthly x 11 months, then periodically
    • Heart rate and BP monthly x 12 months, then periodically

Dose Adjustments:

  • Discontinue for any adverse effect that has not resolved within 28 days or grade ≥ 3 while on 100 mg/day.

Dose Adjustments for hematologic toxicity: **MINIMUM dose 100 mg/day**

Platelets < 100 K

(Monitor CBC weekly until resolved)

1st Occurrence: HOLD* until platelets ≥ 100 K

Resume same dose

However, if < 75K, reduce dose by 100 mg

2nd Occurrence: HOLD* until platelets ≥ 100K

Reduce by 100 mg/day

ANC < 1.0 or

Hg < 8 g/dL

(Monitor CBC weekly until resolved)

HOLD* until ANC ≥ 1.5 or Hg ≥ 9 g/dL

Reduce dose by 100 mg/day

* Hold for maximum of 28 days. Discontinue if not resolved within 28 days or if dose reduction needed beyond 100 mg/day.

Patient-Centered Activities

  • Provide Oral Chemotherapy Education (OCE) Sheet
  • Take once daily, with or without food
  • Taking at bedtime may minimize nausea
    • Moderate to high emetogenic risk per NCCN guidelines
  • Advise patients of warnings:
    • Myelodysplastic syndrome/Acute myeloid leukemia
    • Bone marrow suppression
    • Cardiovascular effects (hypertension, tachycardia)
    • Embryo-fetal toxicity
  • Consider weekly home blood pressure and heart rate monitoring
  • Recommend stool softeners/laxatives as needed for constipation
  • Recommend home antiemetic as needed for nausea/vomiting
    • 5HT-3 such as: Ondansetron

Financial Assistance

  • Quick start and bridge program
  • Commercially insured patients

References:

  1. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. NEJM. 2016; 375 (22): 2154 – 64.
  2. Moore KN, Mirsa MR, Matulonia UA. The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. 2018; 149: 214 – 220.
  3. National Comprehensive Cancer Network. Antiemesis (Version 2.2018). https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf Accessed May 17, 2018.
  4. National Comprehensive Cancer Network. Ovarian cancer (Version 2.2018). https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf Accessed May 15, 2018.
  5. Niraparib incidence and management of thrombocytopenia. TESARO Response letter; 2018.
  6. Retrospective analaysis of the NOVA trial to assess potential predictors for early dose modification. TESARO Response Letter; 2018.
  7. Gonzalez A, Mirza MR, et al. A Prospective Evaluation of tolerability of niraparib dosing based upon baseline body weight and platelet count. Annals of Oncology (2018) 29 (suppl_8): vii332-vii358.10.1093/annonc/mdy285
  8. ZEJULA [Package Insert]. Waltham, MA: Tesaro, Inc.

 

Important notice: National Community Oncology Dispensing Association, Inc. (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.
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Written By: Joshua Nubla, PharmD, NCODA

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Description: This PQI is developed to provide guidance to genomic testing with respect to selpercatinib.

Background: RET-altered cancers include both RET fusions and RET mutations. Both alterations involve activating RET signaling pathways that promote unwanted cell proliferation in cancers. NCCN guidelines for NSCLC include a Category 2A recommendation for RET testing as part of broad molecular profiling in routine clinical practice. In multiple guidelines, RET testing is considered as part of a larger initial panel or secondary single analyte test following negative results for other genetic variants such as EGFR, ALK, and ROS1. Molecular testing within RET-mutated medullary thyroid cancer (MTC) is applicable as approximately 50% of patients with sporadic MTC have somatic RET mutations. In American Thyroid Association, NCCN, and ESMO guidelines, RET testing should be considered within the MTC space. Next generation sequencing (NGS) analyzes DNA and/or RNA when detecting RET. This method requires a small amount of tissue for multiplex testing for many common and rare cancer-related biomarkers. Tissue testing is often considered as RET alteration may not be found in the blood through liquid biopsy and up to 30% of RET alterations can be missed if only ctDNA is tested. There are multiple testing methods for RET that will help determine patient eligibility for selpercatinib, noting that indicated tumor types are associated with specific alterations (Review Supplemental Information section for approved indications).

RET alteration to testAssociated tumor type(s)
RET-fusionNSCLC, Thyroid
RET-mutationMTC

 

PQI Process:

  • Consider the following preferred testing methods when planning for RET genomic testing:
    • Next generation sequencing (NGS) when applicable
      • Account for 2-4 weeks for test completion
      • Both DNA and RNA-based NGS testing methods are appropriate and care team should discuss the general advantages and disadvantages of both
        • RNA-based NGS is able to reveal unbiased fusion information and there are no intron coverage issues 5,10
      • Reverse Transcription-PCR
        • Quick and relatively inexpensive; test completion with 1-2 days
        • PCR testing is designed predominantly for fusions and RET fusion frequency is underestimated
      • FISH
        • High rate of false positive/false negative
        • Should only be considered in rare circumstances (ex. if NGS or RT-PCR are not available)
      • Provide testing schedule to patient 

Patient Centered Activities:

Supplementary Information:

Selpercatinib is a kinase inhibitor indicated for the treatment of:

  • Adult patients with metastatic RETfusion-positive non-small cell lung cancer (NSCLC)*
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy*
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RETfusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)*

*This indication is approved under accelerated approval based on overall response rate and duration of response15

References:

  1. Normanno N, Denis MG, Thress KS, et al. Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced non-small-cell lung cancer. 2017;8(7):12501-12516. https://doi.org/10.18632/oncotarget.13915.
  2. Meric-Bernstam F, Johnson A, Holla V, et al. A decision support framework for genomically Informed investigational cancer therapy. 2015;107(7). https://doi.org/10.1093/jnci/djv098
  3. Drilon A, Hu ZI, Lai GG, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167. https://doi.org/10.1038/nrclinonc.2017.175.
  4. Mulligan LM. RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer. 2014;14(3):173-186. https://doi.org/10.1038/nrc3680.
  5. Garinet S, Laurent-Puig P, Blons H, Oudart JB. Current and future molecular testing in NSCLC, what can we expect from new sequencing technologies? J Clin Med. 2018;7(6):144. https://doi.org/10.3390/jcm7060144.
  6. Lee SE, Lee B, Hong M, et al. Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma. Mod Pathol. 2015;28(4):468-479. https://doi.org/10.1038/modpathol.2014.107.
  7. Chen F, Clark DP, Hawkins AL, et al. A break-apart fluorescence in situ hybridization assay for detecting RET translocations in papillary thyroid carcinoma. Cancer Genet Cytogenet. 2007;178(2):128-134. https://doi.org/10.1016/j.cancergencyto.2007.07.006.
  8. Musholt TJ, Staubitz JI, Cámara RJ, et al. Detection of RET rearrangements in papillary thyroid carcinoma using RT-PCR and FISH techniques – a molecular and clinical analysis. Eur J Surg Oncol. 2019;45(6):1018-1024. https://doi.org/10.1016/j.ejso.2018.11.009.
  9. Go H, Jung YJ, Kang HW, et al. Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma. Lung Cancer. 2013;82(1):44-50. https://doi.org/10.1016/j.lungcan.2013.07.009.
  10. Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res. 2015;21(16):3631-3639. https://doi.org/10.1158/1078-0432.CCR-14-2683
  11. Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(suppl 4):iv192-iv237. http://dx.doi.org/10.1093/annonc/mdy275. Published correction appears in Ann Oncol. 2019;30(5):863-870. http://dx.doi.org/10.1093/annonc/mdy474
  12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Guideline for Thyroid Carcinoma V.1.2020. © National Comprehensive Cancer Network, Inc 2020. Accessed June 19, 2020. To view the most recent and complete version of the guideline, go online to org.
  13. Wells SA Jr., Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610. http://dx.doi.org/10.1089/thy.2014.0335.
  14. Pacini F, Castagna MG, Brilli L, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(suppl 7):110-119. https://doi.org/10.1093/annonc/mds230.
  15. RETEVMO® [package insert]. Lilly USA, LLC, Indianapolis, IN.
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.
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Written by: Michelle Hoa and Natasha Heimbigner, PharmD – Summit Cancer Centers
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Description: Patients undergoing cancer treatment are more susceptible to infections due to their compromised immune system. This PQI will review which vaccinations cancer patients can or cannot use for the proper protection against preventable infections.

Background: Cancer treatments weaken the immune system rendering it more susceptible to infections.1,2 In order to prevent these infections, cancer patients can either take antimicrobial prophylaxis, get vaccinated, or avoid contact with germs.2 Generally, it is best to get vaccinated prior to the start of cancer therapy. Live vaccines should be administered at least four weeks prior to the start of chemotherapy and/or at least 3 months after completion of treatment.1,3 Inactive vaccines should be administered 2 weeks prior to the start of therapy for maximal effect, however, they can be given during therapy. Patients vaccinated during chemotherapy treatment with an inactive vaccine should consider revaccination at least 3 months after therapy as they could be rendered ineffective.3

PQI Process:

  • Obtain patient vaccination history and reference with CDC recommendations to ensure they are current.
  • Determine type of vaccination chemotherapy patient needs.
    • Non-replicating (inactive) vaccines: should be given at least 2 weeks before the initiation of chemotherapy or other immunosuppressive therapy to maximize immune response.1
      • For a healthy immune system, it typically takes up to 2 weeks after vaccination for the immune system to respond to exposed pathogen. Immunocompromised patients may have reduced or no response to vaccine, which may hinder the effectiveness of immunity for patient. Vaccination, 2 weeks prior to chemotherapy, allows immune systems to build an immune response against the targeted pathogen.
      • Antibody response is suboptimal if given vaccination during immunosuppressive therapy but is better than not vaccinating.1
      • The immune response to vaccine antigens is not as good as that of an immunocompetent patient; repeat vaccination or boosters may be beneficial in prolonging immunity.4
    • Replicating live vaccines: should be given at least 4 weeks prior to and at least 3 months after immunosuppressive therapy.1
      • Live vaccinations contain a weak live version of the virus it is intended to vaccinate against; however, an immunocompromised system will not be able to fight against it. The live virus could cause vaccine-derived infections
      • An adequate immune response usually occurs 3 to 12 months after the completion of chemotherapy. Patients should wait at least 3 months after the completion of therapy to receive live vaccination.5
      • Vaccination should be delayed for at least 6 months after treatment if the patient is receiving anti-B-cell antibodies.2
    • Based on chemotherapy regimen, guide patients to reference the package insert for all oncolytic specific vaccination suggestions.

Patient Centered Activities:

  • If patient has not been vaccinated, counsel patient on the importance of vaccination.
  • Patients who are immunocompromised are at higher risk for certain diseases; additional vaccines are recommended.4
    • Immunocompromised patients recommended to receive TIV and polysaccharide-based vaccines (PCV, PPV, MCV4, MPSV, and Hib vaccines).8
    • Flu vaccine:
      • Do NOT get nasal mist flu vaccine since it is a live vaccine.
      • Influenza-related hospitalization is 3 to 5 times higher in cancer patients.
    • Pneumococcal vaccine (PCV13 and PPV23)
      • Immunocompromised children and adults should receive PCV13 and are recommended to receive PPV23 vaccine about 8 weeks later.8 Patients then receive a second dose of PPV23 5 years after the first PPV23.8
      • Patients that received at least one dose of PPV23 should receive PCV13 no sooner than 1 year after last PPV23 dose.8
      • Help patients with weak immune systems fight off serious lung, blood, or brain bacterial infections.7
      • Beneficial for patients with multiple myeloma, lung cancer, chronic lymphocytic leukemia, and lymphoma.1
    • Zostavax® vs Shingrix:®
      • Zostavax® is a live attenuated vaccine (contraindicated in immunocompromised).
      • Shingrix® is an inactivated recombinant vaccine (not recommended due to its lack of research).9
    • COVID-19 Vaccine:
      • Moderna – two doses, 4 weeks apart
      • Pfizer-BioNTech – two doses, 3 weeks apart
      • Johnson and Johnson – one dose
      • Booster – Immune compromised/cancer patients receive a booster of the same vaccine as their initial immunization, at least 4 weeks after the completion of initial immunization.
    • Counsel patients who are on immunotherapy on vaccination recommendations and precautions.
    • Counsel patients who are on immunotherapy on vaccination recommendations and precautions.
      • Immunotherapy has variable immunomodulatory and immunosuppressive effects. Patients undergoing immunotherapy may or may not experience a suppressed immune response.
      • Vaccine may be triggering an exaggerated immune response in certain patients.11
        • Reports suggest that influenza vaccines given to patients on certain types of immunotherapy triggered an amplified immune-related adverse reaction.10,11
        • Some patients receiving immune checkpoint inhibitors experienced intensified immune response.11
      • Consult with prescriber if vaccination is appropriate with current immunotherapy.
    • Follow up with patient 3 months after chemotherapy is complete.
      • If patient had inactive vaccine during treatment, remind patient to revaccinate 3 months post-treatment.
      • If patient is over 65 or has an altered immune system, the CDC recommends a flu vaccine every year and pneumonia vaccine (PPSV23) every 5 years. PCV13 vaccine should only be given once.
      • Booster Tdap vaccination should be considered for patients who have completed chemotherapy.1 Tdap booster should also be given every 10 years since last Tdap/Td vaccination.
    • Counsel family on risk of receiving live vaccines around patients undergoing chemotherapy.

References:

  1. Ariza-Heredia, Ella J, and Roy F Chemaly. “Practical Review of Immunizations in Adult Patients with Cancer.” Human Vaccines & Immunotherapeutics 11.11 (2015): 2606–2614.
  2. nccn.org/patients/resources/life_with_cancer/managing_symptoms/infections.aspx
  3. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm
  4. Centers for Disease Control and Prevention. Recommendations of the advisory committee on immunization practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. Morbidity and Mortality Weekly Report. 1993;42(RR-4). Available from: https://dosinghealth.com/wp-content/uploads/2017/09/rr4204.pdf
  5. https://www.medscape.com/viewarticle/413557
  6. http://chemocare.com/
  7. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/infections/vaccination-during-cancer-treatment.html
  8. https://www.pharmacytimes.com/news/cdc-committee-high-risk-adults-should-get-2-pneumococcal-vaccines
  9. https://www.cdc.gov/vaccines/vpd/shingles/hcp/shingrix/faqs.html
  10. https://www.cancernetwork.com/oncology-journal/immunizing-cancer-patients-which-patients-which-vaccines-when-give
  11. https://www.pharmaceutical-journal.com/news-and-analysis/news/influenza-vaccine-may-cause-exaggerated-immune-response-in-patients-on-cancer-immunotherapy/20202682.article?firstPass=false

Supplemental Information:

Table 1: Types of Vaccines

Type of ImmunizationPrinciple of ActionExamplesComments
Non-replicating vaccinesBased on toxoid, protein subunits, bacterial, antigens, or immunogenic proteins obtained with recombinant, technology.Tetanus, diphtheria, pertussis, poliomyelitis, hepatitis B, influenza, varicella zoster (shingles) (Shingrix®), Haemophilus influenza, pneumococcus, meningococcus, COVID-19Usually requires 3–5 doses; antibody titers diminishes with time
Replicating live vaccinesProduced by disabling the virulent properties of a disease-producing virus or bacteriumMeasles-mumps-rubella, varicella (chicken pox), varicella zoster (shingles) (Zostavax®)  intranasal influenza, yellow fever, oral polio, oral typhoidSevere reactions are possible; transmission of live pathogen may occur; most provide immunity with 1 dose
Passive immunizationAntibodies are infused to provide short-term protectionVaricella Immunoglobulin, hepatitis B immunoglobulinProtection diminishes after weeks or months

 

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.
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Written by: Jon Suyko Pharm.D., BCPS UCHealth Highlands Ranch
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Description: The purpose of this PQI is to discuss the option of using isatuximab-irfc (Sarclisa) for multiple myeloma patients who have been refractory to one to three prior lines of therapy or have had two prior treatment therapies including treatment with lenalidomide and a proteasome inhibitor.

Background: Isatuximab-irfc is an intravenous infused monoclonal antibody which selectively binds to the CD38 glycoprotein found on the surface of malignant plasma cells. Isatuximab-irfc has multiple mechanisms of action.

ICARIA-MM was a phase 3 trial which compared the regimen of isatuximab-irfc plus pomalidomide and low dose dexamethasone to pomalidomide plus low dose dexamethasone alone in patients who received two or more prior therapies including lenalidomide and a proteasome inhibitor.3 The triplet therapy of isatuximab-irfc plus pomalidomide and low dose dexamethasone reduced the risk of disease progression or death by 40% compared to pomalidomide plus dexamethasone alone.4 In the IKEMA study, isatuximab-irfc plus carfilzomib and dexamethasone was compared to carfilzomib and dexamethasone alone. This combination reduced the risk of disease progression or death by 45% compared to carfilzomib and dexamethasone alone.6

PQI Process:

  • Pre-medication is recommended to reduce risk of infusion related reactions5
    • Dexamethasone 40 mg either oral or IV x 1 dose. If patient is ≥ 75 years then give 20 mg
    • Acetaminophen 650 mg-1000 mg x 1 dose
    • H2 antagonist x 1 dose (ex: famotidine 20 mg)
    • Diphenhydramine 25 mg-50 mg orally or IV. Note: IV route is preferred for the first four infusions
    • Review institutional policy to consider using montelukast (usage not required)
  • Verify dosing of isatuximab-irfc is 10 mg/kg intravenous infusion every week for 4 weeks (induction) followed by every 2 weeks in combination with pomalidomide and dexamethasone or carfilzomib and dexamethasone until disease progression or unacceptable toxicity
    • Dosing is based on patient’s actual body weight at the beginning of each cycle
  • Isatuximab-irfc is available in 100mg/5ml vials and 500mg/25 ml vials
  • Preparation: isatuximab-irfc is compatible with 0.9% Sodium Chloride (NS) and 5% Dextrose (D5W)
  • The infusion bag may be gently swirled to create a homogenous mixture. Do Not Shake
  • Binding of isatuximab-irfc to CD38 of red blood cells may result in a false positive indirect coombs test

Table 1: Rate of infusion for isatuximab-irfc5

VolumeInitial rateNo infusion reactionRate IncrementMaximum Rate
First infusion250 ml25 ml/hrFor 60 minutes25 ml/hr every 30 minutes150 ml/hr
Second Infusion250 ml50 ml/hrFor 30 minutes50 ml/hr for 30 minutes then increase by 100ml/hr every 30 minutes200 ml/hr
Subsequent Infusions250 ml200 ml/hr200 ml/hr

Patient Centered Activities:

  • Patient Education
    • Infusion related reactions may occur (38-46%)3, 7 with the administration of isatuximab-irfc. These usually occur with the first infusion and in most cases, resolve on the same day. Infusion reactions may include difficulty breathing, cough, chills and nausea and should counsel patient to report symptom4
    • Coordinate with patient and outside pharmacy (if needed) filling of oral medication(s)
    • Discuss diarrhea management
      • See Oncolytic Induced Diarrhea PQI
    • Patient should report any symptoms of low grade fever, chills, sweating, sore throat, cough/shortness of breath, and increases in blood pressure
  • Monitoring
    • Monitor blood counts and blood pressure
    • Monitor for symptoms of low grade fever, chills, sweating, sore throat, cough/shortness of breath

Supplemental Information:

Sanofi CareASSIST Program6

  • Patient’s with commercial or private insurance may be eligible for $0 copay; No income requirement
  • Copay covers any product-specific copay, coinsurance, and insurance deductibles up to $25,000 in assistance per year
  • Patient’s are responsible for costs which exceed the $25,000/year maximum benefit
  • CareASSIST not available for Medicare, Medicaid, Veterans Affairs/Department of Defense, TRICARE, or similar federal or state programs

References:

  1. Trudel, Suzanne. “Incorporating Isatuximab in the Treatment of Multiple Myeloma.” The Lancet, vol. 394, 7 Dec. 2019, pp. 2045–2046.
  2. Moreno, Laura, et al. “The Mechanism of Action of the Anti-CD38 Monoclonal Antibody Isatuximab in Multiple Myeloma.” Clinical Cancer Research, vol. 25, no. 10, 15 May 2019.
  3. Martin, Thomas, et al. “Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab.” Cells, vol. 8, no. 1522, 26 Nov. 2019.
  4. Attal, Prof. Michael, et al. “Isatuximab plus Pomalidomide and Low-Dose Dexamethasone versus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma (ICARIA-MM): a Randomised, Multicentre, Open-Label, Phase 3 Study.” The Lancet, vol. 394, no. 10214, 7 Dec. 2019, pp. 2096–2107.
  5. Sarclisa®(isatuximab-irfc) Package Insert.
  6. Moreau P (2020) Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA): Interim analysis of a phase 3, randomized, open label study. (#LB2603) EHA25 Virtual, June 14th 2020.
Important notice: National Community Oncology Dispensing Association, Inc. (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.
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