Optimizing Bispecific Antibody Therapy in Multiple Myeloma: A Resource Guide for Nurse and Patient Navigators

Academy of Oncology Nurse & Patient Navigators: Mission and Vision

The mission of the Academy of Oncology Nurse & Patient Navigators (AONN+) is to advance the role of patient navigation in cancer care and survivorship care planning by providing a network for collaboration and development of best practices for the improvement of patient access to care, evidence-based cancer treatment, and quality of life during and after cancer treatment. Cancer survivorship begins at the time of cancer diagnosis. One-on-one patient navigation should occur simultaneously with diagnosis and be proactive in minimizing the impact treatment can have on quality of life. In addition, navigation should encompass community outreach to raise awareness targeted toward prevention and early diagnosis, and must encompass short-term survivorship care, including transitioning survivors efficiently and effectively under the care of their community providers.

The vision of AONN+ is to increase the role of and access to skilled and experienced oncology nurse and patient navigators so that all patients with cancer may benefit from their guidance, insight, and personal advocacy.

Faculty

Elizabeth Aronson, MSN, FNP-BC, OCN
Clinical Nurse Practitioner
Inpatient Bone Marrow Transplant and Immune Effector Cell Therapies
The Mount Sinai Hospital
New York, NY

Jenai Wilmoth, RN
Research Nurse
Hematology, Bone Marrow Transplant & Cancer Immunotherapy Program
Helen Diller Comprehensive Cancer Center
University of California, San Francisco
San Francisco, CA

AONN+ would like to acknowledge the efforts and dedication of oncology nurses Elizabeth Aronson, MSN, FNP-BC, OCN, and Jenai Wilmoth, RN, who dedicated their knowledge, time, and efforts to enhance the care of patients with cancer through the development of this guide.

The endorsement mark certifies that the information presented in educational seminars, publications, or other resources is reliable and credible.

Introduction

The therapeutic landscape of multiple myeloma (MM) has undergone a remarkable evolution over the past 2 decades. The development and application of novel agents and new generations of drugs, such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibody (mAb)-based therapies, have resulted in improved prognosis and extended survival of patients with MM.^1-4 Although these therapeutic advances are opportune and transformative, they add complexity to the MM clinical algorithms.³ The clinical contexts of relapsed/refractory MM (RRMM), in particular, are increasingly heterogeneous and complex, with patients presenting with RRMM after exposure to several classes of novel drugs in earlier lines and a wide variety of prior therapies.^1,3,4 The expanding therapeutic options and increasing complexity of MM treatment algorithms make it challenging for healthcare professionals to stay abreast of many aspects of MM management, including the mechanism of action (MOA) of novel agents; clinical safety and efficacy profiles; strategies for optimizing novel therapies based on best practices for treatment sequencing and adverse event (AE) management; and engaging, educating, and supporting patients and their caregivers to optimize therapeutic outcomes and patient quality of life (QOL).^5-8

Navigators play an integral role in managing and supporting patients diagnosed with cancer, including MM, by educating patients and their caregivers about new treatments and their side effects; managing patient expectations; engaging and communicating with patients to facilitate toxicity monitoring and management; and directing appropriate supportive care measures.^9-11

This resource guide is a review of bispecific antibodies, one of the new therapies currently being studied in clinical trials for patients with RRMM, and best practices for oncology nurses and nurse and patient navigators, social workers, care coordinators, and advanced practice providers in supporting patients with RRMM who may be eligible for bispecific antibody-based treatment.

Overview of MM and the Treatment Journey of Patients with RRMM

MM is the second most common hematologic malignancy; 34,470 new cases and 12,640 deaths are projected in the United States in 2022.¹² MM is a systemic and incurable, but treatable, malignancy of plasma cells that often involves multiple sites within the bone marrow.^13-15 The uncontrolled proliferation and accumulation of malignant plasma cells that produce an abnormal antibody (called M-protein or monoclonal immunoglobulin) can cause bone marrow failure.^14,16 The clinical presentation of MM includes bone pain/osteolytic lesions/fractures, anemia, hypercalcemia, higher susceptibility to infection, and renal insufficiency.¹⁶

Despite the significant advances over the past 2 decades, which have improved the 5-year survival rate from 31.8% to 56.9%,^1,12 nearly all patients eventually relapse, with patients receiving multiple lines of therapy (LOT) for RRMM.^1,17,18 Moreover, patients with RRMM who receive multiple LOT continue to experience poor prognosis in the current era,¹⁹ and worse survival has been reported in groups such as racial/ethnic minorities and older patients with high-risk cytogenetics.^20,21 As patients with MM treated in the current era often receive triplet, and even quadruplet, regimens that combine multiple classes of agents as first-line treatment, there is a continued need for novel agents and combinations for patients with RRMM, especially those with multidrug-refractory disease.^4,18,22 In addition, the response rates with the limited number of therapies currently available for heavily pretreated RRMM patients are poor.^18,23

In this context, many immunotherapies, including mAbs, antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapies (CAR-T therapies) targeting surface antigens overexpressed in myeloma cells, have been developed and introduced into MM practice in recent years.^24,25 Bispecific antibodies that target both an antigen expressed on the surface of effector cells and a tumor-associated antigen are one of the novel antibody formats to enter the MM therapeutic space.^24,25 In subsequent sections, the MOA and clinical activity of this novel class of antimyeloma therapies are discussed in further detail, with a focus on teclistamab, a bispecific antibody that targets CD3 on T cells and the B-cell maturation antigen (BCMA) on myeloma cells.

Bispecific Antibodies: Formats and MOA

Overview of the MOA of Bispecific Antibodies and Rationale for Use in MM

Bispecific antibodies of interest in MM are designed to engage 2 targets simultaneously: an antigen that is expressed on the malignant plasma cells and a protein expressed on the surface of cytotoxic immune effector cells, such as T cells or natural killer (NK) cells.²⁵ This bispecific binding bridges the MM cell with the effector cell, causing activation of the T/NK-cell, cytokine production, proliferation of the effector cells, and eventually, lysis of malignant plasma cells.^24,26 Unlike mAbs, bispecific antibodies induce T-cell activation without requiring co-stimulation and can therefore promote T-cell–mediated tumor-cell lysis independent of antigen presentation on cells via major histocompatibility complex class 1, T-cell–receptor specificity, or additional T-cell co-stimuli.^24,26 Notably, CD3 is the target on T cells for most bispecific antibodies of interest in MM that are currently being investigated in clinical trials, with some NK-cell antigens and other T-cell targets being investigated in preclinical studies.²⁵ Myeloma antigens of interest in the design of bispecific antibodies include BCMA, orphan G-protein–coupled receptor class C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5), all of which are highly expressed on malignant plasma cells, as well as CD38.^3,25,26

MM is characterized by immune dysregulation. The bone marrow immune microenvironment undergoes remodeling through various mechanisms—impaired T-cell activation and proliferation, reduced dendritic-cell function, and overproduction of regulatory T cells—all of which essentially help MM cells evade the innate immune response, promote MM cell growth, and increase immune tolerance of the malignant cells.^26,27 Indeed, some of these mechanisms, such as decreased proliferation and activation of T cells, have been associated with MM disease progression.^26,27 Therefore, restoring immune function and immune effector-cell–mediated recognition and killing of MM cells is of interest in MM therapy. Bispecific antibodies enable T/NK-cell–mediated myeloma cell lysis by directly bridging immune cells with MM cells.^24,26

Design and Characteristics of Bispecific Antibodies in MM

The design and development of bispecific antibodies in MM is predicated on choosing target antigens that are expressed either solely or at significantly higher levels in myeloma cells, compared with healthy cells. Of the 4 myeloma cell-specific targets under investigation in clinical trials in MM, BCMA and CD38 are also targets of other therapies.²⁸

Most bispecific antibodies of interest that are currently under investigation in clinical studies in MM involve BCMA × CD3 constructs.²⁴ BCMA is a type III transmembrane protein that, along with other proteins, modulates B-cell proliferation and survival, as well as their maturation and differentiation into plasma cells.²⁴ Moreover, BCMA and BCMA ligands are overexpressed in MM cells but not in healthy tissue.^25,29 Based on these data, BCMA has emerged as a promising and favored therapeutic target of immunotherapies in MM.

Teclistamab, a T-cell–redirecting BCMA × CD3 bispecific immunoglobulin G4 (IgG4) antibody (of the category of bispecifics, also referred to as bispecific T-cell engagers), was granted breakthrough therapy designation by the US Food and Drug Administration (FDA) and obtained a favorable opinion for authorization from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA).^30,31 A Biologic License Application seeking approval of teclistamab for the treatment of patients with RRMM was submitted to the FDA in December 2021.³² In August 2022, teclistamab gained conditional marketing authorization from the EMA as monotherapy for the treatment of adult patients with RRMM who received ≥3 prior therapies, including an IMiD, a PI, and an anti-CD38 mAb, and had disease progression on the last therapy.³³

Design and MOA of Teclistamab

Teclistamab is a humanized IgG4 proline, alanine, alanine (PAA) bispecific antibody constructed using the DuoBody platform, which allows for controlled swapping of Fab arms between 2 antibodies (Figure 1).^34-36 Preclinical studies showed that teclistamab recruited T cells to BCMA+ cells in vitro and induced potent and specific T-cell–mediated cytotoxicity of cells expressing various levels of BCMA on their surface.³⁴ In addition, teclistamab promoted cytotoxic activity against MM cells in an ex vivo whole-blood model and ex vivo in bone marrow mononuclear cells from patients with MM.³⁴ Teclistamab also significantly inhibited tumor growth in 2 independent in vivo xenograft MM models.³⁴ These data provide support for the therapeutic potential of teclistamab, which is now being investigated in nearly a dozen clinical trials in MM.

Figure 1. Design and MOA of Teclistamab^24-26,36

Clinical Activity of Teclistamab in MM

Clinical Efficacy of Teclistamab in RRMM in the MajesTEC-1 Study

The Biologic License Application for teclistamab was based on data from MajesTEC-1 (NCT04557098 phase 2, NCT03145181 phase 1), an open-label, multicenter, multicohort, phase 1/2 clinical trial evaluating the safety and efficacy of teclistamab in adults with RRMM who previously received ≥3 LOT (Figure 2).^37-39 In phase 1, the recommended phase 2 dose of teclistamab was identified as a weekly subcutaneous dosage of 1.5 mg/kg, preceded by step-up doses of 0.06 mg/kg and 0.3 mg/kg.³⁸

Figure 2. MajesTEC-1 Study^37-39

In the phase 2 portion of MajesTEC-1, 120 patients were enrolled to receive teclistamab at the recommended phase 2 dose (R2PD) of 1.5 mg/kg.³⁹ As of March 16, 2022, 42.4% of patients continued treatment. The median treatment duration was 8.5 months (range, 0.2-24.4); 59.4% and 47.9% of patients received at least 6 and 9 months of teclistamab treatment, respectively. The median relative dose intensity for all treatment cycles, including step-up doses, was 93.7%.³⁹ The median age of the cohort was 64 years (range, 33-84). Extramedullary disease was present in 17.0%; 25.7% of those with available cytogenetic data had ≥1 high-risk cytogenetic abnormalities, defined as del(17p), t(4;14), or t(14;16). Patients had received a median of 5 previous LOT (range, 2-14); 70.3% had received ≥2 IMiDs, ≥2 PIs, and ≥1 anti-CD38 mAb (penta-drug exposure); a majority (77.6%) had triple-class refractory disease, and nearly a third (30.3%) had penta-drug refractory disease.³⁹

Overall, 63% (95% confidence interval [CI], 55.2-70.4) of enrolled patients who received ≥1 dose of teclistamab (as of September 7, 2021) had a response (Table 1); the overall response rate (ORR) included patients who achieved stringent complete response, complete response, very good partial response, and partial response, as assessed by an independent review committee.³⁹ The response data, including the rates of patients with complete response who achieved minimal residual disease-negative status, are summarized in Table 1. Minimal residual disease status was assessed using next-generation sequencing in MajesTEC-1, with a sensitivity threshold of 1 tumor cell per 105 bone marrow cells.³⁹ The minimal residual disease-negativity rate shown in Table 1 is based on the minimal residual disease-negative patients among the all-treated population (44 of 165 patients, 26.7%); of 54 patients who were minimal residual disease-evaluable in the study, 44 (81.5%) were minimal residual disease-negative.³⁹

Table 1. Summary of MajesTEC-1 Response Data³⁹

The responses were durable and deepened over time; median duration of response (DOR) was 18.4 months (95% CI, 14.9 to not estimable) and had not yet matured.³⁹ The median time to first response was 1.2 months (range, 0.2-5.5), and the median time to best response was 3.8 months (range, 1.1-16.8). The Kaplan-Meier estimate of maintenance of response for ≥12 months was 68.5% (95% CI, 57.7-77.1). The median progression-free survival was 11.3 months (95% CI, 8.8-17.1). The median overall survival was 18.3 months (95% CI, 15.1 to not estimable) and had not yet matured (Table 2).³⁹

Table 2. Medium PFS and OS in the MajesTEC-1 Study³⁹

In MajesTEC-1, response criteria included serum and urine MM markers at day 1 of each treatment cycle, assessment of bone marrow aspirate, and imaging to confirm a complete response (negative immunofixation of serum and urine) and if progressive disease was suspected.³⁹ Although the treatment response was not associated with the maximum change in cytokine levels or T-cell activation, response was associated with higher levels of cytokines, compared with the levels in patients who did not respond. These data suggest that the immune activation that occurred early after treatment initiation may be a predictor of clinical response to teclistamab.³⁹ The ongoing MajesTEC-4 phase 3 study is evaluating the addition of teclistamab to lenalidomide for the treatment of patients with newly diagnosed MM.

“Patients should be advised that the inflammatory response, including cytokine release syndrome (CRS), is an expected consequence of teclistamab activity attacking their disease and should not be viewed as an undesirable effect. CRS related to teclistamab was low grade in the majority of patients, ie, mild to moderate symptoms. No deaths occurred related to toxicity, and CRS was managed effectively in most patients with supportive care and tocilizumab and, less commonly, steroids or oxygen.” —Elizabeth Aronson, MSN, FNP-BCN, OCN

“Patients should be monitored in the hospital during the step-up dosing and full dose for CRS. CRS is usually an indicator of response to the bispecific T-cell engagers (BiTE). We like to see signs and symptoms of CRS such as fevers and C-reactive protein elevations, which show a response to the treatment.” —Jenai Wilmoth, RN

Immunogenicity and pharmacokinetics: No teclistamab antibodies were detectable in any of the 146 patients treated with the teclistamab at the R2PD evaluable for immunogenicity. Soluble BCMA levels decreased rapidly and were sustained over 4 cycles in evaluable patients who had a partial response or better but increased in those without a response. Reductions in soluble BCMA levels were greater in patients with a deeper response.³⁹

Subgroup analyses of data from the MajesTEC-1 study indicated consistent responses across clinically relevant patient subgroups, including those with high-risk cytogenetic abnormalities, penta-drug refractory disease (except those with extramedullary disease), stage III disease, and presence of ≥60% plasma cells in the marrow.³⁹ Moreover, the data suggested that patients who received ≤3 prior LOT may have a better response rate than those who have received >3 therapies (albeit with wide confidence intervals); this finding supports the use of teclistamab in earlier LOT.³⁹

Overall, the data from the MajesTEC-1 study showed that a once-weekly subcutaneous dose (1.5 mg/kg after step-up dosing) of teclistamab induced deep and durable responses in patients with triple-class–exposed RRMM, providing another therapeutic option in this clinical setting with limited options.³⁹

Ongoing/Additional Clinical Studies of Teclistamab in MM

Teclistamab is also under investigation in combination with other agents in MM (Table 3). Preclinical studies demonstrated the synergistic antimyeloma activity of teclistamab in combination with the anti-CD38 mAb daratumumab.⁴⁰ The combination immunotherapy effectively killed MM cells ex vivo, including those from heavily pretreated MM patients, providing support for clinical investigation of this combination.⁴⁰ Teclistamab in combination with daratumumab is being investigated in several clinical trials in RRMM, including the MajesTEC-3 phase 3 study.⁴¹

Table 3. Other Clinical Studies of Teclistamab in MM

In the phase 1b TRIMM-2 study of the combination of teclistamab and daratumumab for patients with RRMM, initial data demonstrated tolerable safety and promising efficacy, without overlapping toxicities.⁴² Updated data from this study showed an overall response rate (ORR) of 78% among the 37 evaluable patients treated with the combination, with 73% achieving very good partial response or better.⁴² Median time to first response across dosing cohorts was 1.0 month (range, 0.9-2.8 months) and the median DOR was not reached. Treatment with the combination resulted in upregulation of CD38+/CD8+ T cells and proinflammatory cytokines, indicating potential synergy of the combination in patients with prior anti-CD38 exposure.⁴² MajesTEC-2, a phase 1b multi-arm study, is investigating the safety, tolerability, and optimal dose of teclistamab administered in different combination regimens, including with daratumumab, bortezomib, and IMiDs, in patients with MM.⁴³

Safety Profile of Teclistamab in the MajesTEC-1 Study

Overall, AEs were common in the MajesTEC-1 study, with all 165 patients reporting an AE and 94.5% reporting grade 3 or 4 AEs (Table 4).³⁹ The most common AEs were hematologic, including neutropenia (70.9%), anemia (52.1%), and thrombocytopenia (40.0%). Injection-site reactions (all grade 1 or 2) were reported in 26.1%.³⁹ Transfusion and growth factor support may be indicated for some patients with hematologic AEs.

Table 4. Summary of AEs Reported in ≥15% of Patients in the MajesTEC-1 Study.³⁹

Cytokine release syndrome (CRS)³⁹: CRS occurred in 72.1%. Most CRS events occurred after step-up and cycle 1 doses, with CRS occurring in 3.6% of patients cycle ≥2. It is important to note that most CRS events were grade 1 or 2 in severity and fully resolved, except for 1 grade 3 event, which occurred in a patient with concurrent pneumonia and resolved in 2 days. No patients discontinued teclistamab due to CRS. The median time until CRS onset was 2 days (range, 1-6) after the most recent dose, and the median duration was 2 days (range, 1-9). Supportive measures for CRS management were provided to 110 patients (66.7%); these treatments included the administration of tocilizumab (36.4%), low-flow oxygen by nasal cannula (12.7%), and glucocorticoids (8.5%). A single vasopressor was administered in 1 patient (0.6%). Additional supportive measures that may be required, but not specified in the study, include acetaminophen for fevers and meperidine for rigors.

Neurotoxicity³⁹: Investigator-assessed neurotoxic events, including immune effector-cell–associated neurotoxicity syndrome (ICANS), were reported in 14.5% of patients. Most events were grade 1 or 2, except for 1 grade 4 seizure that occurred in a patient with bacterial meningitis during cycle 7. Neurotoxic AEs did not lead to teclistamab discontinuation in any patient. Headache, determined by the investigator to be the most frequent teclistamab-related neurotoxic event, was reported in 8.5%. In all, 5 patients had a total of 9 events of ICANS, all either grade 1 or 2. Supportive measures used for management of teclistamab-associated AEs are summarized in Table 4.

Principles of Navigation for Managing Patients Receiving Teclistamab Therapy

Role of the Navigator

The care and treatment of patients with MM involves multidisciplinary teams (MDTs), with navigators playing an integral role within the MDT.⁴⁷ Key navigator functions throughout the patient’s journey through the MM care continuum are depicted in Figure 3. In essence, the navigator’s central role is to address barriers to care, acting as a patient advocate and educator throughout their healthcare journey.^9,11,47,48

Figure 3. Role of the Navigator in the Multiple Myeloma Care Continuum

The responsibility and core competencies for oncology nurse navigators (ONNs), as described by the Academy of Oncology Nurse and Patient Navigators (AONN+), fall within 4 broad functional domains: coordination of care, overcoming healthcare-system barriers, education, and professional role as oncology nurse.¹¹

Coordination of care includes a range of responsibilities throughout the care continuum, especially for the MM patient. The MDT managing MM patients includes surgeons, radiologists, and medical oncologists as well as other members such as nurse practitioners, financial navigators, pharmacists, and social workers.¹¹ ONNs serve as a clinically informed liaison, enabling communications between the MDT and the patient to ensure that the patient’s interaction across MDT members is productive. In addition to coordinating the testing, treatment, and follow-up appointments for the patient, navigators also play a key role in ensuring care continuity, such as when patients continue treatments, posttreatment follow-ups, and long-term evaluations in community practice.¹¹ Inclusion of ONNs as part of the MDT for patients with gastrointestinal cancer, for example, shortened the interval between diagnosis and treatment and reduced missed appointments.⁴⁹ Care improvements such as earlier diagnosis, treatment by a high-volume specialist, and reduced time to treatment have been reported in other studies evaluating the impact of navigators on oncology practice.^50-52

Educating patients and their caregivers is one of the fundamental mandates for navigators.^11,53 MM is a challenging diagnosis for patients and their caregivers, and patients with RRMM are a heterogeneous group, with different prior therapies and disease courses.^4,54 Navigators can help provide patients and caregivers with critical and tailored information on their specific disease setting; the tests that may be required prior to, during, and after treatment; available treatment options; potential side effects of treatments; and how to watch for and report any AEs to the care team.¹¹ A recent survey-based analysis of the management of lung cancer patients showed that nurse navigators/clinic administrators were more likely to distribute patient education materials than oncologists and pulmonologists across practice settings.⁵⁵ These findings highlight the key role of nurse navigators as the primary point of contact for patients. Improving the health literacy of patients and caregivers can facilitate shared decision-making (SDM) in MM practice.⁵⁶ Indeed, the involvement of navigators was shown to improve SDM rates for patients with cancer, providing opportunities for improved cancer screening, diagnosis, treatment, and care coordination.^51,57-60 For example, ONNs were reported to not only provide symptom management education to patients with lung cancer, but they also assessed and monitored the symptoms of their patients, enabling personalized care delivery.⁵⁷

Another key aspect of patient education in MM practice is to set patient expectations to ensure that the MDT and the patient are aligned in their understanding of the therapeutic goals and that patients are prepared for their treatment journey.⁵⁴ Studies of patient perspectives in MM highlight the importance of managing expectations as an important component of therapeutic decision-making.^54,61

Given the significant impact of the MM patient journey on their mental health, including mental health-related QOL, psychological distress, and anxiety, as well as the critical role of and impact on their caregivers, navigators can also help educate, engage, and support caregivers, family members, and friends of patients with MM.^62-65

Navigators can help identify the informational, financial, and emotional needs of caregivers and facilitate interventions to address these unmet needs, thereby improving the QOL of caregivers of patients with MM.⁶⁵

Navigators can also provide a venue for patients and their caregivers to discuss their concerns and fears, facilitating the patient–caregiver communication along their cancer journey.⁶⁴

One of the core responsibilities that navigators are tasked with is to help address barriers to care access. In MM practice, numerous barriers to care and practice gaps have been identified, including the contribution of a patient’s age, race/ethnicity, rural/urban residence, socioeconomic status, and insurance type.^66,67 Navigators, in their role as patient advocates throughout the care journey, can help reduce racial disparities in care and address other barriers to care by identifying and referring patients for clinical trial enrollment; screening patients who are at risk of financial toxicity and helping implement suitable interventions to address financial concerns (such as reviewing insurance coverage and referring patients to financial/copay assistance programs); and planning and coordinating emotional/psychosocial support.^48,68-71

The RRMM patient journey is often long and complex, with the potential for multiple relapses requiring treatment with novel therapies and/or clinical trial enrollment (Figure 4). Moreover, treatment options for RRMM continue to evolve, which can make it even more challenging for patients and caregivers to understand medical terminology and unfamiliar terms, even if they have undergone prior treatment. Navigators can provide timely and meaningful information to patients with MM and connect them to resources, thereby empowering the patient to become engaged and well-informed participants in their own care journey.¹¹

Figure 4. The Complexity of the MM Patient Journey

The final core competency for navigators in the MM MDT is their role as a professional clinician in applicable cases, such as with advanced practice providers or oncology nurses. In their clinical role, navigators may perform many functions, including ensuring safe and reliable care delivery, commensurate with guideline-directed evidence-based treatment practices and Quality Oncology Practice Initiative safety standards; conducting patient triage for decisions on treatments, hospitalization, and interventions for potential AEs; and communicating regularly with referring physicians and the MDT.^9,72-74 For example, immunotherapy nurse navigators were identified as one approach for optimizing the outcomes for patients receiving immunotherapies, such as bispecific antibody-based treatment.⁷³ Indeed, a real-world study showed that nurse navigators successfully implemented toxicity screening tools in hematology-oncology clinics in a broad range of cancer types, resulting in referrals to multiple supportive services.⁷⁴

Overall, there is a large body of evidence underscoring the importance of navigators in cancer care. As the roles and responsibilities of navigators with different skills, place in the MDT, and clinical/nonclinical responsibilities continue to evolve, an improved awareness of novel therapies in MM, the RRMM patient journey, and best practices for optimizing MM management can inform their practice and foster patient- and practice-level improvements in outcomes.

Best Practices for Optimizing Teclistamab Therapy

Teclistamab is delivered subcutaneously, making it amenable to administration in an outpatient setting.^39,75 However, as with other therapeutic options for patients with MM, specific supportive care measures and monitoring protocols are important for patients who may be candidates for or who receive teclistamab therapy. The safety profile of teclistamab from the MajesTEC-1 study has been discussed previously; AEs and the corresponding supportive measures in patients treated with teclistamab in this study are summarized in Table 5.

Table 5. AEs and Corresponding Supportive Measures with Teclistamab^39,76

“Monitoring and management is a huge educational piece that all patients need to be aware of and that the nurse navigator needs to become familiar with.” —Jenai Wilmoth, RN

“Developing a working understanding of CRS and immune effector-cell–associated neurotoxicity syndrome will be invaluable to nurse navigators as more immune therapies are approved and utilized for a variety of malignancies. Nurse navigators should understand the cardinal signs of CRS (fever, fever, fever!) and neurotoxicity (altered mental status, lethargy, dysgraphia, headache, and expressive aphasia) and the need for rapid evaluation and intervention.” —Elizabeth Aronson, MSN, FNP-BCN, OCN

Clinical Efficacy/Toxicity Profile of Teclistamab and Other BCMA-Directed Therapies for MM

To date, 3 BCMA-directed therapies have been approved for use in patients with RRMM: the antibody–drug conjugate belantamab mafodotin and the 2 CAR-T therapies, idecabtagene vicleucel and ciltacabtagene autoleucel.^77,78 Although cross-trial comparisons should be interpreted with caution, the response rate observed with teclistamab (63%) in the MajecTEC-1 study compares favorably to that of belantamab mafodotin (31% in the DREAMM-2 study in triple-refractory RRMM).³⁹ Although the response rates in patients who received approved BCMA-directed CAR-T therapies and underwent apheresis (67%-83%) were higher than that with teclistamab, teclistamab is an “off-the-shelf” immunotherapy that is associated with rapid response (within the first month of treatment), is not associated with long wait times (for apheresis appointments or engineered T-cell production), and can be administered subcutaneously (CAR T cells are delivered via infusion, primarily in specialty care centers in an inpatient setting).^39,79

Conclusions

Teclistamab and other bispecific antibodies are poised to enter the MM therapeutic space, providing welcome and much-needed new therapeutic options, especially for patients with MM whose disease has relapsed or is refractory to multiple classes of drugs. Teclistamab is an “off-the-shelf” immunotherapy that has demonstrated favorable response rates in patients with RRMM, with deep and durable responses seen in patients with exposure to 3 major classes of drugs: PI, IMiD, and anti-CD38 mAb. It is important for navigators to stay abreast of these new clinical developments in MM, including the MOA, class-specific and unique toxicities/side effects, and the clinical safety and efficacy data for teclistamab and bispecific antibodies, as well as best practices for supporting patients who may be candidates for or receive bispecific antibody therapies such as teclistamab. Improved familiarity with these key concepts can help navigators translate clinical advances to improved outcomes and QOL for patients with MM.

“With the imminent FDA approval of teclistamab and the issues surrounding the accessibility of CAR-T therapies for patients with MM, this directed therapy may become the therapy of choice for oncologists providing care to these patients.” —Jenai Wilmoth, RN

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