Expert clinical framework report: Management of adverse events related to novel therapies for relapsed/refractory multiple myeloma (RRMM)

Authors

  • Jill Lacey, BSc, BSP, ACPR Senior Hematology Pharmacist, Saskatchewan Cancer Agency, Saskatoon, SK
  • Joanne Hewitt, PhD, NP Nurse Practitioner, Cancer Care Alberta, Cross Cancer Institute, Edmonton, AB
  • Jennifer L. Daley-Morris, RPh, BPharm Manager, Oncology Pharmacy and Systemic Therapy Suite, Southlake Regional Health Centre, Newmarket, ON
  • Judith James, RN, BSc Research Nurse Coordinator, Capital District Health Authority, Halifax, NS
  • Jonathan Stevens, BPharm, ACPR Clinical Pharmacist in Hematology, Saint John Regional Hospital, Saint John, NB
  • Olivier Blaizel, BPharm Pharmacist, Hôpital Charles-Le Moyne, Longueuil, QC

DOI:

https://doi.org/10.58931/cht.2022.1S1130

Abstract

Multiple Myeloma (MM) is a malignancy of the plasma cells accumulating in the bone marrow. MM develops stepwise from the premalignant conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).

The Canadian Cancer Society estimates that in 2022 4,000 Canadians will be diagnosed, and 1,650 will die from MM. Survival rates have improved over the years with the development of novel treatment strategies, including proteasome inhibitors (PI), immunomodulatory drugs (IMiDs), targeted antibody and cellular therapies, and a selective inhibitor of nuclear export (SINE), as well as with the use of combinations of drugs. Although a number of patients will have a durable response following high-dose chemotherapy and autologous stem cell transplant (ASCT), MM remains an incurable malignancy with the majority of patients relapsing and eventually developing refractory disease (RRMM).

Collaborative environments, in which pharmacists work with hematologists/oncologists, nurse practitioners, and supportive care teams, have been shown to improve adherence to the treatment plan. Prescription of appropriate prophylaxis in combination with various treatment strategies may reduce the number and duration of treatment delays. Intensified clinical and pharmaceutical care, including medication management and structured patient counseling for patients on oral anticancer drugs, has been shown to reduce the number of medication errors and severe side effects while improving the patient’s treatment experience. Nurses play a vital role in the management of toxicities as they educate, support, and advocate for patients.

This report discusses the management of adverse events (AEs) related to both established agents and novel therapies for the optimal management of patients with RRMM. Established and novel therapies are often used in combination, which presents the potential for overlapping toxicities. The optimal combination therapies including the sequencing of various regimens are yet to be determined. Basic research and clinical trials with investigational agents are ongoing in an effort to improve both the depth and duration of response in newly diagnosed patients and those with RRMM with the aim of finding the best treatment options for every patient.

Author Biographies

Jill Lacey, BSc, BSP, ACPR, Senior Hematology Pharmacist, Saskatchewan Cancer Agency, Saskatoon, SK

Jill Lacey obtained a Bachelor in Pharmacy degree from the University of Saskatchewan in 2008 and then completed an accredited pharmacy residency program. She has been working in malignant hematology since 2010, with both inpatient and outpatient experience. Jill has been the Senior Hematology Pharmacist at the Saskatoon Cancer Centre since 2019.

Joanne Hewitt, PhD, NP, Nurse Practitioner, Cancer Care Alberta, Cross Cancer Institute, Edmonton, AB

Dr. Joanne Hewitt is a doctoral prepared oncology nurse practitioner with a focus on multiple myeloma and plasma cell dyscrasias at the Cross Cancer Institute in Edmonton, Alberta. Her Interests include research activities, staff and patient education, and mentorship. She received the 2021 CANO Pfizer Award of Excellence in Nursing Leadership.

Jennifer L. Daley-Morris, RPh, BPharm, Manager, Oncology Pharmacy and Systemic Therapy Suite, Southlake Regional Health Centre, Newmarket, ON

Jennifer Daley-Morris is currently the Manager of the Oncology Pharmacy and Systemic Therapy Suite at the Stronach Regional Cancer Centre at Southlake in Newmarket, Ontario.

Judith James, RN, BSc, Research Nurse Coordinator, Capital District Health Authority, Halifax, NS

Judith James is currently a Research Nurse Coordinator at the QEII Health Sciences Center in Halifax, Nova Scotia. Judith has 27 years of nursing experience in the field of Hematology/Oncology, and for the last 10 years has focused her career on Hematology Research.

Jonathan Stevens, BPharm, ACPR, Clinical Pharmacist in Hematology, Saint John Regional Hospital, Saint John, NB

Jonathan Stevens is a graduate from the Memorial University School of Pharmacy and completed a hospital pharmacy residency at the Saint John Regional Hospital. He holds a clinical practice in outpatient hematology focusing on patient education, monitoring and toxicity management. He is working towards his PharmD at Memorial University.

Olivier Blaizel, BPharm, Pharmacist, Hôpital Charles-Le Moyne, Longueuil, QC

Olivier Blaizel graduated from Université de Montréal in 1996. After practicing for two years in community pharmacies, he turned to hospital pharmacy practice. He has now been at Hôpital Charles-Le Moyne for nearly 20 years, where he has been coordinator of the oncology pharmacy since 2004. His practice focuses mainly on outpatients but he also works with patients on the hospital ward.

References

Brenner DR, Poirier A, Woods RR, et al. Projected estimates of cancer in Canada in 2022. CMAJ. May 2 2022;194(17):E601-E607. doi:10.1503/cmaj.212097 DOI: https://doi.org/10.1503/cmaj.212097

Sweiss K, Wirth SM, Sharp L, et al. Collaborative Physician-Pharmacist-Managed Multiple Myeloma Clinic Improves Guideline Adherence and Prevents Treatment Delays. J Oncol Pract. Nov 2018;14(11):e674-e682. doi:10.1200/JOP.18.00085 DOI: https://doi.org/10.1200/JOP.18.00085

Durr P, Schlichtig K, Kelz C, et al. The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents. J Clin Oncol. Jun 20 2021;39(18):1983-1994. doi:10.1200/JCO.20.03088 DOI: https://doi.org/10.1200/JCO.20.03088

Colson K. Treatment-related symptom management in patients with multiple myeloma: a review. Support Care Cancer. May 2015;23(5):1431-45. doi:10.1007/s00520-014-2552-1 DOI: https://doi.org/10.1007/s00520-014-2552-1

Cengiz Seval G, Beksac M. The safety of bortezomib for the treatment of multiple myeloma. Expert Opin Drug Saf. Sep 2018;17(9):953-962. doi:10.1080/14740338.2018.1513487 DOI: https://doi.org/10.1080/14740338.2018.1513487

Richardson PG, Delforge M, Beksac M, et al. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia. Apr 2012;26(4):595-608. doi:10.1038/leu.2011.346 DOI: https://doi.org/10.1038/leu.2011.346

Miceli TS, Gonsalves WI, Buadi FK. Supportive care in multiple myeloma: Current practices and advances. Cancer Treat Res Commun. 2021;29:100476. doi:10.1016/j.ctarc.2021.100476 DOI: https://doi.org/10.1016/j.ctarc.2021.100476

Dimopoulos MA, Roussou M, Gavriatopoulou M, et al. Cardiac and renal complications of carfilzomib in patients with multiple myeloma. Blood Adv. Feb 28 2017;1(7):449-454. doi:10.1182/bloodadvances.2016003269 DOI: https://doi.org/10.1182/bloodadvances.2016003269

Kumar S, Moreau P, Hari P, et al. Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma. Br J Haematol. Aug 2017;178(4):571-582. doi:10.1111/bjh.14733 DOI: https://doi.org/10.1111/bjh.14733

Chavda SJ, Pocock R, Cheesman S, et al. Association of hypertension and cardiac events in patients with multiple myeloma receiving carfilzomib: practical management recommendations. Br J Haematol. Sep 2020;190(5):e312-e316. doi:10.1111/bjh.16889 DOI: https://doi.org/10.1111/bjh.16889

Cornell RF, Ky B, Weiss BM, et al. Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma. J Clin Oncol. Aug 1 2019;37(22):1946-1955. doi:10.1200/JCO.19.00231 DOI: https://doi.org/10.1200/JCO.19.00231

Plummer C, Driessen C, Szabo Z, Mateos MV. Management of cardiovascular risk in patients with multiple myeloma. Blood Cancer J. Feb 26 2019;9(3):26. doi:10.1038/s41408-019-0183-y DOI: https://doi.org/10.1038/s41408-019-0183-y

Fotiou D, Roussou M, Gakiopoulou C, et al. Carfilzomib-associated renal toxicity is common and unpredictable: a comprehensive analysis of 114 multiple myeloma patients. Blood Cancer J. Nov 3 2020;10(11):109. doi:10.1038/s41408-020-00381-4 DOI: https://doi.org/10.1038/s41408-020-00381-4

Faiman B, Doss D, Colson K, Mangan P, King T, Tariman JD. Renal, GI, and Peripheral Nerves: Evidence-Based Recommendations for the Management of Symptoms and Care for Patients With Multiple Myeloma. Clin J Oncol Nurs. Oct 1 2017;21(5 Suppl):19-36. doi:10.1188/17.CJON.S5.19-36 DOI: https://doi.org/10.1188/17.CJON.S5.3-6

Geyer HL, Viggiano RW, Lacy MQ, et al. Acute lung toxicity related to pomalidomide. Chest. Aug 2011;140(2):529-533. doi:10.1378/chest.10-2082 DOI: https://doi.org/10.1378/chest.10-2082

Yamamoto J, Ito T, Yamaguchi Y, Handa H. Discovery of CRBN as a target of thalidomide: a breakthrough for progress in the development of protein degraders. Chem Soc Rev. Aug 1 2022;51(15):6234-6250. doi:10.1039/d2cs00116k DOI: https://doi.org/10.1039/D2CS00116K

Ebied M, Chan V. Multidisciplinary Professional Roles Addressing Needs in Multiple Myeloma: An Innovative ‘Virtual’ Pharmacist Surveillance Clinic. Semin Oncol Nurs. Aug 2021;37(4):151173. doi:10.1016/j.soncn.2021.151173 DOI: https://doi.org/10.1016/j.soncn.2021.151173

Musto P, Anderson KC, Attal M, et al. Second primary malignancies in multiple myeloma: an overview and IMWG consensus. Ann Oncol. Feb 1 2017;28(2):228-245. doi:10.1093/annonc/mdw606 DOI: https://doi.org/10.1093/annonc/mdw606

Nahi H, Chrobok M, Gran C, et al. Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma. PLoS One. 2019;14(2):e0211927. doi:10.1371/journal.pone.0211927 DOI: https://doi.org/10.1371/journal.pone.0211927

Frampton JE. Isatuximab: A Review of Its Use in Multiple Myeloma. Target Oncol. Sep 2021;16(5):675-686. doi:10.1007/s11523-021-00827-0 DOI: https://doi.org/10.1007/s11523-021-00827-0

Offidani M, Corvatta L, More S, et al. Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. Front Oncol. 2020;10:624661. doi:10.3389/fonc.2020.624661 DOI: https://doi.org/10.3389/fonc.2020.624661

Darazalex product monograph. Janssen Inc. 2019 Oct 25. Available from: https://pdf.hres.ca/dpd_pm/00053751.PDF.

Lassiter G, Bergeron C, Guedry R, et al. Belantamab Mafodotin to Treat Multiple Myeloma: A Comprehensive Review of Disease, Drug Efficacy and Side Effects. Curr Oncol. Jan 21 2021;28(1):640-660. doi:10.3390/curroncol28010063 DOI: https://doi.org/10.3390/curroncol28010063

Neupane K, Wahab A, Masood A, et al. Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma. J Blood Med. 2021;12:529-550. doi:10.2147/JBM.S317966 DOI: https://doi.org/10.2147/JBM.S317966

Lonial S, Nooka AK, Thulasi P, et al. Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM). Blood Cancer J. May 26 2021;11(5):103. doi:10.1038/s41408-021-00494-4 DOI: https://doi.org/10.1038/s41408-021-00494-4

Richter J, Madduri D, Richard S, Chari A. Selinexor in relapsed/refractory multiple myeloma. Ther Adv Hematol. 2020;11:2040620720930629. doi:10.1177/2040620720930629 DOI: https://doi.org/10.1177/2040620720930629

Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. Nov 14 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3 DOI: https://doi.org/10.1016/S0140-6736(20)32292-3

Nooka AK, Costa LJ, Gasparetto CJ, et al. Guidance for Use and dosing of Selinexor in Multiple Myeloma in 2021: Consensus From International Myeloma Foundation Expert Roundtable. Clin Lymphoma Myeloma Leuk. Jul 2022;22(7):e526-e531. doi:10.1016/j.clml.2022.01.014 DOI: https://doi.org/10.1016/j.clml.2022.01.014

Richard S, Chari A, Delimpasi S, et al. Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk. Am J Hematol. Sep 1 2021;96(9):1120-1130. doi:10.1002/ajh.26261 DOI: https://doi.org/10.1002/ajh.26261

Mikhael J, Noonan KR, Faiman B, et al. Consensus Recommendations for the Clinical Management of Patients With Multiple Myeloma Treated With Selinexor. Clin Lymphoma Myeloma Leuk. Jun 2020;20(6):351-357. doi:10.1016/j.clml.2019.12.026 DOI: https://doi.org/10.1016/j.clml.2019.12.026

XPOVIO product monograph. FORUS Therapeutics Inc. 2022 May 31. Available from: https://pdf.hres.ca/dpd_pm/00066090.PDF.

Jagannath S, Facon T, Badros AZ, et al. Clinical Outcomes in Patients (Pts) with Dose Reduction of Selinexor in Combination with Bortezomib, and Dexamethasone (XVd) in Previously Treated Multiple Myeloma from the Boston Study. Blood. 2021;138(Suppl 1):3793-3793. doi:10.1182/blood-2021-146003 DOI: https://doi.org/10.1182/blood-2021-146003

Gasparetto C, Schiller GJ, Tuchman SA, Callander NS, Baljevic M, Lentzsch S, Rossi AC, Kotb R, White D, Bahlis NJ, Chen CI, Sutherland HJ, Madan S, LeBlanc R, Sebag M, Venner CP, Bensinger WI, Biran N, Ammu S, Ben-Shahar O, DeCastro A, Van Domelen D, Zhou T, Zhang C, Bentur OS, Shah J, Shacham S, Kauffman M, Lipe B. Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients. Br J Cancer. 2022 Mar;126(5):718-725. doi: 10.1038/s41416-021-01608-2 DOI: https://doi.org/10.1038/s41416-021-01608-2

White D, Chen C, Baljevic M, Tuchman S, Bahis NJ, Schiller GJ, et al. Oral selinexor, pomalidomide, and dexamethasone (XPd) at recommended phase 2 dose in relapsed refractory multiple myeloma (MM). J Clin Oncol. 2021;39(15 Suppl):8018. DOI: https://doi.org/10.1200/JCO.2021.39.15_suppl.8018

Hayden PJ, Roddie C, Bader P, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. Mar 2022;33(3):259-275. doi:10.1016/j.annonc.2021.12.003 DOI: https://doi.org/10.1016/j.annonc.2021.12.003

Published

2022-11-15

How to Cite

1.
Lacey J, Hewitt J, Daley-Morris JL, James J, Stevens J, Blaizel O. Expert clinical framework report: Management of adverse events related to novel therapies for relapsed/refractory multiple myeloma (RRMM). Can Hematol Today [Internet]. 2022 Nov. 15 [cited 2024 Dec. 22];1(S11). Available from: https://canadianhematologytoday.com/article/view/30