Key Principles in Safely Prescribing Bispecific Antibodies in Heavily Pretreated Patients With Multiple Myeloma (Part 2)
Welcome to this Clinical Case Series learning module!
Here's how it works:
- Read these 3 case studies on the AP role in managing patients heavily pretreated for multiple myeloma as they receive bispecific antibody therapy. But don't miss the 3 other cases that make up part 1 of this module.
- Answer the poll next to each case to see how your colleagues are managing these patients. You'll see results in real time.
- Continue your learning by watching a recording of a webinar presented by Josh Epworth, MSN, ARNP
Monitoring and Identifying Neurotoxicity in Patients Receiving Teclistamab
Clinical Pearl 2: Expressive aphasia is a highly specific symptom to ICANS.
Mr. R is a 64-year-old male who was diagnosed with lambda light chain multiple myeloma (MM) in 2016. He first presented with ongoing pelvic pain. MRI of the lumbar spine and pelvis exhibited multiple lytic lesions and a pathologic fracture in L3. His laboratory workup is summarized in the table below. Serum protein electrophoresis (SPEP) showed 0.3 g/dL IgG lambda. An MRI of the bone marrow showed multiple lytic lesions in the axial and appendicular skeletons with a large destructive lesion at a size of 5.1 x 2.8 cm in the left posteromedial iliac wing. A bone marrow biopsy comprised 55% plasma cells, with high-risk cytogenetics with a 17p deletion. Mr. R was diagnosed with revised International Staging System stage II IgG lambda MM.
Table. Laboratory Values at MM Diagnosis
| Parameter | Value at Diagnosis |
|---|---|
| Calcium | 9.8 mg/dL |
| Creatinine | 0.71 mg/dL |
| Hemoglobin | 14.0 g/dL |
| Beta-2 microglobulin | 3.2 mg/L |
| Albumin | 3.8 g/dL |
| LDH | 183 U/L |
| Serum free light chains | |
| Kappa | 0.93 mg/dL |
| Lambda | 127 mg/dL |
Mr. R achieved a complete response (CR) to first-line treatment with 6 cycles of carfilzomib, lenalidomide, and dexamethasone. He continued to an autologous stem cell transplant, to which he achieved a stringent CR (sCR). He continued with triplet maintenance therapy for 25 months, until his disease progressed. Mr. R then received 4 cycles of daratumumab, pomalidomide, and dexamethasone with stable disease. Upon progression, he started on elotuzumab, lenalidomide, and dexamethasone. However, lenalidomide was switched to pomalidomide due to a recurrent rash. His disease progressed after 2 cycles of elotuzumab, pomalidomide, and dexamethasone. Mr. R then received selinexor for 1 cycle due to refractory gastrointestinal symptoms. The next line of treatment included 3 cycles of isatuximab, carfilzomib, and dexamethasone, but did not result in a response. Doxorubicin, bortezomib, and dexamethasone were attempted for 2 cycles, but Mr. R’s disease continued to progress. After bridging with bortezomib, doxorubicin, cisplatin, cyclophosphamide, etoposide, and lenalidomide (Kd-PACE) for 1 cycle, he received idecabtagene vicleucel. However, Mr. R progressed after 2 months. At this point in his journey, teclistamab was initiated in the inpatient setting.
Mr. R exhibited grade 1 cytokine release syndrome (CRS) 1 day following his initial dose of teclistamab with a fever of 38.1 degrees Celsius that was managed with a single dose of acetaminophen without recurrence. Twelve hours following his day 4 dose of teclistamab, he exhibited a shift in his immune effector cell encephalopathy (ICE) score from 10 to 9, with an increase in difficulty maintaining attention while counting backward from 100 by 10s.
Neurologic symptoms can occur for multiple reasons, including infection, electrolyte imbalances, significant hypertension, or hepatic failure. Immune effector cell associated neurotoxicity syndrome (ICANS) has features that are similar to those seen with other types of encephalopathies, but it has the specific characteristic of aphasia, initially expressive but can progress to global, but can also include altered level of consciousness, decreased cognitive capacity, weakness, and seizures.1 Per the American Society of Transplant and Cellular Therapy (ASTCT), in the setting of immunotherapy, the term “neurotoxicity” has been replaced with “immune effector cell associated neurotoxicity syndrome” (ICANS). However, in many papers the terms are used interchangeably.1 In MajesTEC-1, ICANS occurred in 6% of cases, with most events developing during step-up dosing, and the median onset was 4 days with a median duration of 3 days.2 The grade of ICANS is determined by a host of factors and guides the level of intervention. One of the initial assessments for ICE includes assessments of orientation, naming, following commands, writing, and attention on a point system to determine the presence and severity of encephalopathy; the higher the score, the lesser the impact of ICANS. The ICE score is then combined with level of consciousness, presence and severity of seizures, and motor findings, as well as presence of raised intracranial pressure/cerebral edema.
Levetiracetam 500 mg twice daily was initiated, and neurology was consulted. Tocilizumab was considered, but given that the CRS had resolved by the time the ICANS symptoms developed, it was ultimately not used. Mr. R’s attention returned to baseline at his next ICE assessment, and he has not exhibited any further episodes of CRS or ICANS in the interim. Following discharge, Mr. R has tolerated teclistamab without difficulty for 3 months, achieving a very good partial response.
References
- Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625-638.
- TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use. [Prescribing information]. Horsham, PA: Janssen Biotech, Inc.; October 2022.
Evaluating Infection Risk With Teclistamab
Clinical Pearl: The risk of infection is elevated during treatment with teclistamab in the setting of well-controlled multiple myeloma (MM) and normal white blood cells and absolute neutrophil counts.
Ms. P is a 55-year-old female who was diagnosed with IgG kappa MM in 2019. She first presented with ongoing fatigue, back pain, and recurrent upper respiratory and urinary tract infections with elevated total protein. An x-ray of the thoracic spine indicated multiple lytic lesions but no pathological fractures. The results of the laboratory workup is summarized in the table below. The results of the serum protein electrophoresis (SPEP) was 2.2 g/dL IgG kappa. A PET/CT showed multiple sites of metabolically active lytic lesions throughout the axial skeleton, but no pathologic fractures. The bone marrow biopsy comprised 30% to 40% plasma cells, with high-risk cytogenetics with a 17p deletion, t(4;14). Ms. P was diagnosed with revised International Scoring System stage II IgG kappa MM.
Table. Laboratory Values at MM Diagnosis
| Parameter | Value at Diagnosis |
|---|---|
| Calcium | 8.8 mg/dL |
| Creatinine | 1.02 mg/dL |
| Hemoglobin | 8.9 g/dL |
| Beta-2 microglobulin | 5.0 mg/L |
| Albumin | 2.6 g/dL |
| LDH | 223 U/L |
| Serum free light chains | |
| Kappa | 23.7 mg/dL |
| Lambda | 1.2 mg/dL |
The initial treatment was carfilzomib, lenalidomide, and dexamethasone. Ms. P achieved a complete response (CR) and then underwent an autologous stem cell transplant. She received triplet maintenance therapy due to her high-risk status. After a progression-free survival of 18 months, she received daratumumab, bortezomib, and dexamethasone, to which she achieved a very good partial response (VGPR), with disease progression after 8 months. This was followed by treatment with elotuzumab, pomalidomide, and dexamethasone, which resulted in stable disease for 5 months. Upon disease progression, a bone marrow biopsy exhibited a new t(11;14). Venetoclax, carfilzomib, and dexamethasone was initiated, and Ms. P achieved a partial response for 4 months. At disease progression, teclistamab was initiated in the inpatient setting without difficulty and transferred treatment to the outpatient setting. Ms. P had an excellent response to treatment, achieving a persistent VGPR. Unfortunately, she developed progressive hypogammaglobulinemia, with an IgG at 201 mg/dL at 2 months following the start of therapy as well as recurrent episodes of neutropenia. She had 3 infections (including COVID-19) with 1 hospitalization. Although her insurance initially declined the request for intravenous immunoglobulin (IVIG), it was eventually approved and initiated.
In the MajesTEC-1 trial, infection was a significant adverse event, occurring in 76.4% of patients with 44.8% reporting grade 3-4 infections, even in the setting of effective suppression of disease.1 In heavily pretreated patients, there is an increased risk of opportunistic infection due to disease and treatment-related immunocompromise. In addition, the risk of infection may be increased by immune effector cell therapy that targets BCMA, which can deplete B cells and plasma cells, resulting in hypogammaglobulinemia and neutropenia and subsequent infections. Management of this issue should include identification of baseline infections prior to the start of teclistamab; frequent monitoring for immunoglobulin depression and neutropenia; assessment of infection; as well as consideration of the use of antimicrobial and IVIG prophylaxis and granulocyte colony-stimulating factor (G-CSF), as needed. Given the complexity of these infections consulting with an infectious disease team may be prudent.2
Since starting IVIG approximately 2 months ago, Ms. P has reported no new infections and her most recent IgG was 410 mg/dL (whereas her nadir was 201 mg/dL prior to starting IVIG). She continues to receive teclistamab, and her disease remains in VGPR.
References
- Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387:495-505.
- Mohan M, Nagavally S, Dhakal B, et al. Risk of infections with B-cell maturation antigen-directed immunotherapy in multiple myeloma. Blood Adv. 2022;6:2466-2470.
Transferring Patients Receiving Teclistamab From an Academic Center to a Community Clinic
Clinical Pearl: Following the step-up dosing, the risk of adverse effects is lower than during initial dosing. With appropriate planning and monitoring, teclistamab can be safely administered in the community setting.
Ms. T is a 67-year-old female with a diagnosis of IgA lambda multiple myeloma (MM) that was diagnosed in 2017. She initially presented to the local emergency department with severe pain in her right hip. An x-ray of the site indicated a fracture in the femoral neck and findings of lytic lesions in the right pelvis. Results from Ms. T’s laboratory workup are summarized in the table below. The result of the serum protein electrophoresis (SPEP) was 3.5 g/dL IgA lambda. A PET/CT showed multiple sites of metabolically active lytic lesions throughout the axial skeleton, a compression fracture in L3, and a fracture in the right femoral neck. A bone marrow biopsy comprised 80% plasma cells, with no high-risk cytogenetics. Ms. T was diagnosed with revised International Staging System stage II IgA lambda MM.
Table. Laboratory Values at MM Diagnosis
| Parameter | Value at Diagnosis |
|---|---|
| Calcium | 10.3 mg/dL |
| Creatinine | 1.39 mg/dL |
| Hemoglobin | 8.5 g/dL |
| Beta-2 microglobulin | 4.1 mg/L |
| Albumin | 4.0 g/dL |
| LDH | 199 U/L |
| Serum free light chains | |
| Kappa | 0.61 mg/dL |
| Lambda | 117.4 mg/dL |
Ms. T was initially treated with modified lenalidomide, bortezomib, and dexamethasone (RVD lite, given over a 35-day cycle) at her community clinic. She achieved a complete response (CR) and deferred autologous stem cell transplant, and instead started lenalidomide maintenance therapy. After a progression-free survival of 27 months, her disease did progress. She then received pomalidomide and dexamethasone, again in the community setting, and achieved stable disease. Daratumumab was added to her regimen, and she then experienced a CR. Daratumumab was continued as single-agent maintenance therapy; she went 18 months without progression. Her next regimen was bortezomib and prednisone, to which she had a very good partial response (VGPR) before switching to ixazomib during a COVID-19 outbreak. Ms. T experienced progression after 15 months. Per her local provider’s suggestion, she consulted with an academic center to review treatment options. It was ultimately decided to proceed with teclistamab.
During initial dosing with teclistamab, Ms. T exhibited grade 1 cytokine release syndrome (CRS) after her second dose, but had an otherwise unremarkable start to therapy and achieved a CR. However, she had been coming to the academic center for weekly infusions for 4 months and expressed frustration at having to drive 2 hours each way. She questioned what options were available at her rural, community clinic.
Between 15%-19% of the American population lives outside a major metropolitan center, and a rural environment is a strong predictor of outcomes across the cancer continuum.1 In Ms. T’s case, her local oncologist had been providing excellent care and frequently consulted with colleagues in academic settings. With her new regimen, Ms. T was requesting that her local provider assume responsibility for the administration of teclistamab to minimize the amount of travel she would have to do to continue this regimen. The local oncologist expressed confidence in being able to manage her care; however, concerns were expressed within the community clinic regarding management of possible CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). These concerns were addressed following educational opportunities at the community clinic. The staff there came to understand that, like daratumumab, the acute adverse events are typically limited to early dosing; Ms. T was far beyond the high point of risk. Further discussions were had regarding the ongoing risk of infection and monitoring approaches. Following this, the infusions were taken over by her local clinic and Ms. T remains in a CR with no significant issues.
References
- Blake KD, Moss JL, Gaysynsky A, et al. Making the case for investment in rural cancer control: An analysis of rural cancer incidence, mortality, and funding trends. Cancer Epidemiol Biomarkers Prev. 2017;26:992-997.
Meet the Faculty
Josh Epworth
MSN, ARNP
Nurse Practitioner, Hematology Oncology
Fred Hutchinson Cancer Center
Josh Epworth is a nurse practitioner at the Fred Hutchinson Cancer Center, where he has treated plasma cell malignancies for nearly a decade. In addition to working with patients on active treatment, Josh manages the Multiple Myeloma Maintenance and Monitoring Clinic (M4 Clinic). This is an APP staffed clinic for patients whose multiple myeloma is under control with maintenance or monitoring alone. The purpose of this clinic is to watch for indications of progression of disease, manage maintenance-related side effects, and improve access to active care teams for patients with new and relapsing multiple myeloma.
Let us know what you'd like to learn more about at jadpro-editor@broadcastmed.com