HJNO Jan/Feb 2024

HEALTHCARE JOURNAL OF NEW ORLEANS I  JAN / FEB 2024 55 Lesley Meng, MD Medical Oncologist Mary Bird Perkins Cancer Center Terrebonne General from two different antibodies — one target- ing a tumor-specific antigen and the other targeting the effector T cell. T cells are re- cruited at the tumor site to kill the cancer. Teclistamab and elranatamab are agents approved to treat RRMM. They are readily available and administered subcutaneously in gradually increasing doses over the first week, followed by weekly dosing. Many trials have been conducted to as- sess the median duration of progression- free survival (PFS), overall survival (OS), and the objective response rate (ORR) of these RRMM patients. The Cartitude-1 tri- al showed cilta-cel was associated with a 27-month PFS and an OS of greater than 55%. The KarMMa trial revealed a PFS of 8.8 months and an OS of 19.4 months with the use of ide-cel. The MajesTEC-1 trial showed a median duration of PFS of 11.3 months and an ORR of 63% noted with the use of teclis- tamab. CRS occurred in 74% of patients and neurotoxicity was noted in 15%. The Mag- netisMM-1 trial revealed elranatamab was associated with a median PFS of 11.8months and an ORR of 64%. Both BiTE cell agents revealed high response rates greater than 60% at 14 months with a complete response approaching 30%. Survival is relatively poor among pa- tients who develop RRMM after triple class therapeutic treatment. These patients usually have a poorer performance status yet achieve high response rates with im- munotherapeutic agents and improved progression-free survival over that noted with standard chemotherapy regimens for multiple myeloma withmanageable adverse effects. The primary adverse effects of the above agents include a cytokine release syn- drome (CRS), which can be managed with tocilizumab and steroids and a less frequent immune effective cell associated with a neu- rotoxicity syndrome (ICANS). The trials not- ed above have shown that immunotherapy can be offered to patients who have failed three or more standard chemotherapy regi- mens for multiple myeloma with relatively good tolerability and a higher objective re- sponse rate than that seen with standard chemotherapy. n REFERENCES 1 Lin, Y; Martin, T.G.; Usmani, S.Z.; et al. “CAR- TITUDE-1 final results: Phase 1b/2 study of cilt- acabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myelo- ma.” Journal of Clinical Oncology 41, issue 16 sup- plemental (June 01, 2023): 8009-8009. https:// ascopubs.org/doi/10.1200/JCO.2023.41.16_sup- pl.8009 2 Rodriguez-Otero, P.; Ailawadhi, S.; Arnulf, B.l; et al. “Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma.” New England Journal of Medicine 388, no. 11 (March 16, 2023) :1002-1014. doi: 10.1056/NEJMoa2213614 3 Moreau, P.; Garfall, A.; van de Donk, N.W.C.J.; et. al, “Teclistamab in Relapsed or Refractory Mul- tiple Myeloma.” New England Journal of Medi- cine 387, no. 6 (August 11, 2022): 495-505. doi: 0.1056/NEJMoa2203478 4 Jakubowiak, A.J.; Bahlis, N.J.; Raje, N.W.; et al. “Elranatamab a BCMA targeted T cell redirect- ing immunotherapy, for patients with relapsed or refractory multiple myeloma Updated results from MagnetisMM-1.” Journal of Clinical Oncolo- gy 40, issue 16 supplemental (June 2, 2022). doi: 10.1200/JCO.2022.40.16_suppl.8014 Lesley Meng, MD, is a medical oncologist who prac- tices atTerrebonne General | Mary Bird Perkins Can- cer Center and is board-certified in internal medicine, hematology, and medical oncology. She has over 15 years of experience in the medical field as a hematologist oncologist. Meng earned her Doctor of Medicine degree from the Louisiana School of Medicine and a Master of Business Administra- tion degree fromSoutheastern Louisiana University. She completed an internal medicine residency at Louisiana State University Health Sciences Center and completed a hematology/oncology fellowship there as well. Meng compassionately commits to patient care with her patient-centered approach. MULTIPLE MYELOMA is a cancer of the blood where a specific type of white blood cell, plasma cells, multiply and become can- cerous in the bone marrow. Undetectable cells resistant to treatment continue to sur- vive and grow until the multiple myeloma is detectable. Due to the viability of these treatment resistant cells, newer therapies are used to eradicate these cells using a different mechanism of action. Immuno- therapy boosts the immune system to fight cancer. For relapsed and refractory mul- tiplemyeloma (RRMM), immunotherapeutic agents are available, which target the B cell maturation antigen (BCMA) expressed on differentiated plasma cells, including tumor cells in multiple myeloma. BCMAcan be tar- geted using chimeric antigen receptor (CAR) T cells or a bispecific BCMA-directed CD3 T cell engager (BiTE). These therapies are approved for triple class refractory disease where the disease did not respond to a pro- teosome inhibitor, an immunomodulatory agent, and an anti CD38 antibody. CAR T cell therapy involves extracting the patient’s own immune cells (T cells) from their blood and genetically modifying them in a laboratory to express chimeric antigen receptors on their surface. These modified cells are then multiplied in number. Lym- phodepleting chemotherapy is then given to create space to make room for the CAR T cells to be infused back into the patient. These CAR T cells seek out and attack the cancer cells. Ide-cell and cilta-cel are ex- amples of CAR T cell agents approved to treat RRMM. This therapy is given as a single dose yet takes weeks to become available. The half-life with these agents is long. BiTE therapy is not created out of the patient’s own personal immune cells. They are recombinant proteins made of two scFv