Key Interventions for Patients on BCMA-Targeted Bispecific Antibody Therapy

Samantha Shenoy, NP, UCSF Health, San Francisco, California, explains the treatment course of a patient diagnosed with kappa light chain myeloma and discusses key interventions when caring for a patient on BCMA-targeted bispecific antibody therapy.

Transcript: 

Hello, I'm Samantha Shenoy. I'm the research nurse practitioner at UCSF Medical Center in San Francisco, California in the hematology oncology department. Today I'm excited to share a case with you about a patient with relapsed/refractory multiple myeloma.

This case is about a 53-year-old, previously healthy female who initially presented to the emergency department with severe back pain and rib pain. Serum studies revealed an elevated calcium level of 13, a creatinine of 2.1 and a hemoglobin of 9.4. Bone marrow biopsy showed 80% plasma cells and FISH was positive for translocation 1114. Albumin was 3.8, beta-2 microglobulin was 5.9 and LDH was 1700. She was diagnosed with kappa light chain myeloma with a kappa light chain level of a 1154. Imaging showed extensive bony involvement and a T9 compression fracture, for which she had a T9 partial corpectomy. International staging system and revised international staging system score was three.

She was started on treatment with cyclophosphamide, dexamethasone, and bortezomib. She received 2 cycles of this regimen and achieved a very good partial response. She then started treatment with carfilzomib, lenalidomide and dexamethasone and achieved a stringent complete response after 4 cycles. She next received a neologist stem cell transplant with mouthful and chemotherapy preparative regimen and achieved a stringent complete response and MRD negativity.

She was on lenalidomide maintenance for 2 years and then had progressive disease. She went on to receive 2 more lines of therapy, progressed after each line and then was changed to teclistamab, a bispecific antibody therapy. During cycle 9 of teclistamab, she presented to the emergency department with worsening shortness of breath and was found to be hypoxic with an oxygen saturation of 89% on room air. She had first started noticing dyspnea on exertion 3 weeks prior to presenting to the ED. She's an avid runner and had to stop multiple times due to shortness of breath, which was abnormal for her.

Symptoms had worsened to the point of having dyspnea on exertion when she walked around the house and she also had a new and worsening cough, which prompted her to go to the ER. CT chest imaging showed new extensive bilateral brown glass opacities predominantly involving the bilateral lower lobes. No evidence of pulmonary embolism. Neutrophil count was 1.09 and dropped to as low as 0.21 over the next several days. Additionally, she was noted to have an IgG level of 141 as she was not able to make it to her previous appointments for intravenous immunoglobulin or IVIG. While in the ED, she also complained of new onset diarrhea and stool samples that were sent were positive for clostridium difficile (c. diff) infection and it was gene and protein positive. Stool studies also tested positive for norovirus infection.

In terms of management, she was initially started on antibiotics with ceftriaxone and azithromycin in the ER. She admitted to the hospital and subsequently advanced to cefepime and azithromycin for fevers. She was given growth factor with GCSF to manage the neutropenia. She received a dose of IVIG while hospitalized. Pulmonary and infectious disease teams were consulted. Notably, the patient was on pneumocystis jirovecii Pneumonia, or PJP prophylaxis with atovaquone as she had a cetra allergy, but she had not been taking it consistently. Further workup was consistent with PJP pneumonia. Based on the patient's poor compliance with the atovaquone and chest CT findings, she started on treatment for PJP pneumonia with primaquine 30 milligrams daily for 21 days, clindamycin 450 milligrams every 6 hours for 21 days, prednisone 40 milligrams twice daily for 5 days, 40 milligrams for 5 days, and then 20 milligrams for 11 days.

She started to show improvement in symptoms and hypoxia after starting this regimen. After completing PJP treatment, she resumed prophylaxis with atovaquone 1500 milligrams daily. Follow-up chest CT 3 months later was negative for infection. Fidaxomicin 200 milligrams by mouth every 12 hours for 10 days was started for the c. diff infection. Patient had persistent diarrhea after she completed the fidaxomicin course and c. diff was resent via stool sample and showed she was gene positive but protein negative, just consistent with colonization. The stool sample was also sent for norovirus and showed that she had a persistently positive norovirus PCR for a few months. She was also given additional IVIG. Subsequently diarrhea improved and she only needed Imodium PRN [pro re nata]. After hospital discharge, described above, cytomegalovirus polymerase chain reaction, or CMV PCR, which is a molecular test used to detect and quantify CMV DNA came back positive at 1100 and she was given 2 weeks of valganciclovir 900 milligrams twice a day to treat the CMV.

CMV PCR was monitored weekly and she was not detected after completing 2 weeks of treatment. Unfortunately, the CMV recurred a couple months later with a viral load of 21,000 and she was restarted on valganciclovir 900 milligrams twice daily after 1 month of treatment. Viral load was undetectable and then she was decreased to valganciclovir 900 milligrams daily for three months and then the valganciclovir was stopped. CMV PCR was monitored monthly and the CMV has not recurred. Of note that the myeloma treatment with teclistamab was stopped after last dose in cycle 9 given her multiple infections. She's remained in stringent CR with no other treatment in the 2 years since treatment has been held.

Moving on to a clinical question, I'm going to give 4 choices here and the question is, what is not a key intervention when caring for someone on BCMA-targeted bispecific antibody therapy? 

1. PJP prophylaxis
2. IVIG replacement per guidelines
3. Neutropenia management with growth factor support after step-up dosing, or;
4. Managing nail changes such as nail loss.

To answer this, numbers 1 through 3 are key interventions while caring for someone on BCMA-targeted bispecific antibody therapies and 4 more refers to bispecific antibody therapy that targets GPRC5D and that's where those patients see those nail changes such as nail loss.

Teclistamab is a bispecific antibody that targets B-cell maturation antigen or BCMA, which is a protein that's highly expressed on the surface of multiple myeloma cells. It's also expressed on normal plasma cells. Patients are at high risk of infection with bispecific antibody therapy that targets BCMA due to the hypogammaglobulinemia and neutropenia seen with these drugs. Ongoing T-cell activation, T-cell exhaustion or treatment induced depletion of some T-cell populations can also contribute to this infectious risk as was described in the IMWG paper, first author is Rodriguez Otero. Patients are also at risk for opportunistic infections such as PJP pneumonia due to suboptimal T-cell and B-cell immunity seen with bispecific antibody therapy.

It's crucial to give IVIG replacement per institutional guidelines for these patients. In addition, a CMV PCR should be monitored monthly or more frequently if needed. Patients should also be on appropriate HSV-VVV prophylaxis and PJP prophylaxis and neutropenia should be managed with growth factor support as needed.

Thank you so much for watching. I hope that this was helpful.