CAR T-Cell Therapy vs Bispecific Antibody vs Standard of Care Treatment in Multiple Myeloma

Clinical Pearl: Consideration of patient goals and psychosocial factors along with shared decision-making can help the patient make the best treatment selection in terms of quality of life and survival benefit

Ms. Green is a 61-year-old female who was diagnosed with multiple myeloma in 2015. At the time, her FISH panel was positive for gain of 1q21 and monosomy 13. She received induction therapy with bortezomib, lenalidomide, and dexamethasone but failed to achieve response after six cycles of therapy. She was then transitioned to carfilzomib, pomalidomide, and dexamethasone and underwent autologous stem cell transplant. Immediately after, she was placed on daratumumab to maintain her response. She unfortunately progressed after three cycles and was transitioned to elotuzumab, pomalidomide, and dexamethasone, with stable disease.

Ms. Green presented for a second opinion from out of town. The advanced practice provider (APP) explained that due to her rapid rate of progression with each line of therapy and because she had only received three lines of therapy so far, which included two proteosome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, she should consider a clinical trial with CAR T-cell therapy vs. bispecific antibody treatment. Current standard of care CAR T-cell therapy options do not permit patients to have received less than four lines of therapy. The APP discussed with Ms. Green the standard of care option of daratumumab, carfilzomib, pomalidomide, and dexamethasone as an alternative to a clinical trial, explaining that this combination may help obtain some degree of control over her disease. A phase 2 study with daratumumab, carfilzomib, and dexamethasone showed an overall response rate of 69% in patients with high-risk disease features and in 90% of standard-risk patients.¹ A phase 1/2b multicenter study evaluating daratumumab, carfilzomib, pomalidomide, and dexamethasone² demonstrated overall partial response rates of 86% with near-complete or complete response rates of 55%, which was higher in the phase 2 Chari 2019 study.¹

Ms. Green’s baseline blood counts were as follows:

Ms. Green favored the clinical trial option of CAR T-cell therapy, as she felt more certain that introducing a novel regimen would obtain a deeper and more durable response. She also discussed treatment sequencing strategies with her team and decided to revisit standard of care options at a later time, as she was offered a CAR T-cell therapy clinical trial slot. Ms. Green was attracted to the option of CAR T-cell therapy as it does not require her to receive routine serial treatments indefinitely. She understood that she must remain within 50 miles of the hospital for the first month for close monitoring. She proceeded to apheresis before starting bridging therapy with daratumumab, bortezomib, and dexamethasone.

References

1. Chari A, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381:727-738.
2. Jasielec J, et al. Daratumumab (dara) plus carfilzomib, pomalidomide, dexamethasone (KPD) in lenalidomide refractory multiple myeloma (mm): A multi-center MMRC study. Blood. 2020;136(Supplement 1):50.

Identifying and Managing CRS and Other Common Adverse Events During CAR T-Cell Therapy

Clinical Pearl: Timely resolution of CRS may prevent more severe serious manifestations without compromising efficacy of CAR T-cell expansion and can improve patient outcomes while maintaining durable responses

Mrs. Small is a 74-year-old female initially diagnosed with multiple myeloma in June 2015. Her prior FISH studies revealed high-risk disease and were positive for deletion 17p, deletion 13q, and t(11;14). Recently, she was found to have progressive disease with a myeloma lesion in the L3 vertebral body as seen on PET/CT, with elevation in her M protein from 0.1 to 0.7 g/dL. She has received four prior lines of therapy, including a proteasome inhibitor, immunomodulatory agent, and monoclonal antibody. Next-line CAR T-cell therapy with idecabtagene vicleucel (ide-cel) was discussed with her.

Mrs. Small continued on her current line fourth-line regimen of elotuzumab, pomalidomide, and dexamethasone while awaiting a slot for ide-cel therapy. During that time, the advanced practice provider (APP) submitted her financial clearance paperwork. A month later, the team was informed that there was an available slot for Mrs. Small, so she proceeded to apheresis. A month later, she underwent lymphodepletion with 3 days of cyclophosphamide and fludarabine. She was subsequently admitted for CAR T-cell therapy, and started D0 of infusion. She experienced fever with a temperature of 39°C (102.2°F) that correlates with cytokine release syndrome (CRS) grade 1 on D1. Her fever did not abate with a dose of acetaminophen, and she continued to complain of chills and rigors. The APP ordered chest x-ray, urine culture, and blood cultures and started her on empiric antibiotics of vancomycin and cefepime. The chest x-ray was negative, and bloodwork showed the following:

The next day, Mrs. Small continued to have CRS grade 1 without evidence of immune effector cell-associated neurotoxicity syndrome (ICANS). She had an immune effector cell (ICE) score of 10/10. Due to continued CRS, she was treated with one dose of tocilizumab with resolution of fever. Her C-reactive protein (CRP) and ferritin levels continued to rise:

On day 4, Mrs. Small experienced anemia with a hemoglobin of 7.2 g/dL requiring blood transfusion; she was started on growth factors for a neutrophil count of 0.5 k/μL. Her CRP started to decrease, and ferritin levels started to plateau thereafter. Her clinical course was insignificant except for a complaint of some diarrhea on D5. Stool and C. difficile cultures came back negative, and the diarrhea resolved with loperamide. She did not have any recurring CRS. Blood and urine cultures continued to be negative. Mrs. Small was discharged on D8 with a follow-up scheduled for 2 days later.