Teclistamab FDA approval biweekly dosing in Relapsed or Refractory Multiple Myeloma (3 KOL Video Interviews Below)

On February 20th, 2024 the Teclistamab FDA approval of TECVAYLI® (teclistamab-cqyv) for biweekly dosing was announced as a significant advancement in the treatment landscape for relapsed or refractory multiple myeloma (RRMM), offering a new beacon of hope for patients battling this incurable blood cancer. This approval underscores the commitment to addressing the complex needs of patients with multiple myeloma, especially those who have shown resistance to previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Understanding Multiple Myeloma and the Need for Advanced Treatments

Multiple myeloma is a plasma cell neoplasm that disrupts the production of normal blood cells in the bone marrow, replacing them with cancerous plasma cells. These malignant cells produce abnormal antibodies that can lead to a variety of complications, such as bone damage, anemia, kidney failure, and more. TECVAYLI®, targeting the B-cell maturation antigen (BCMA) on multiple myeloma cells, represents a novel approach in harnessing the body’s immune system to fight the disease. The drug’s mechanism involves engaging both BCMA on multiple myeloma cells and CD3 on T-cells, promoting a potent immune response against the cancerous cells.

The FDA’s accelerated approval of TECVAYLI® was based on the response rate observed in clinical trials, with the condition that continued approval may depend on further verification of clinical benefits in confirmatory trials. The initial treatment dose of 1.5 mg/kg is designed to offer a balance between efficacy and safety, minimizing the risk of adverse reactions while ensuring a therapeutic effect.

Adverse Reactions: Immune effector cell associated neurotoxicity syndrome (ICANS)

Adverse reactions are a critical consideration in the treatment of RRMM, with the most common including cytokine release syndrome (CRS), neurologic toxicity, injection site reactions, and systemic administration reactions. CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), represent some of the most serious potential side effects. These conditions necessitate careful monitoring and management, including the administration of pretreatment medications and complete blood cell counts to mitigate risks. Injection site reactions, although generally less severe, contribute to the overall burden of treatment and require appropriate care.

The Role of Teclistamab (TECVAYLI®) in Multiple Myeloma Treatment

The decision to approve a biweekly dosing regimen for TECVAYLI® was informed by the drug’s ability to maintain efficacy while potentially reducing the frequency of adverse reactions and improving the quality of life for patients. This dosing flexibility allows for adjustments based on disease progression or the emergence of unacceptable toxicity, offering clinicians the ability to tailor treatment plans to the individual needs of their patients.

The Significance of the MajesTEC-1 Study in TECVAYLI®’s Approval

Patients eligible for TECVAYLI® have typically exhausted several prior lines of therapy, underscoring the drug’s role as a critical option for those with few alternatives. The approval for biweekly dosing is based on evidence from the MajesTEC-1 study, which demonstrated that patients achieving a complete response could safely transition to the less frequent dosing schedule without compromising their response to treatment.

Navigating Treatment Safety and Efficacy with Teclistamab (TECVAYLI®)

Safety remains a paramount concern, with recommendations for the use of antibiotic or antiviral prophylaxis to prevent infections and guidelines for the immediate evaluation of patients presenting with symptoms of neurologic toxicity or elevated liver enzymes. The management of these adverse effects is crucial for ensuring the safety and well-being of patients undergoing treatment with TECVAYLI®.

In summary, the FDA approval of TECVAYLI® for biweekly dosing represents a critical development in the fight against relapsed or refractory multiple myeloma. By offering a novel mechanism of action, flexible dosing schedules, and a focus on patient-centered care, TECVAYLI® provides hope for patients seeking to manage their disease with fewer side effects and greater convenience. As the medical community continues to explore the full potential of this innovative treatment, the goal remains clear: to improve outcomes and quality of life for those affected by this challenging condition.

Philippe Moreau, MD, Presents MajesTEC-1 Study Phase 1/2 Study Findings on Teclistamab for Relapsed or Refractory Multiple Myeloma

The landscape of treatment for relapsed and refractory multiple myeloma is undergoing significant evolution, marked by the development of innovative therapies aimed at addressing the complexities of this challenging disease. A notable advancement in this field is the development of teclistamab, a bispecific antibody targeting the B-cell maturation antigen (BCMA), which has shown promising results in a phase 1/2 study presented by Dr. Philippe Moreau. This article provides an objective analysis of the study’s findings, emphasizing the drug’s safety, efficacy, and potential implications for the treatment of multiple myeloma.

Study Overview

Teclistamab is designed to engage both BCMA on multiple myeloma cells and CD3 on T-cells, thereby activating the immune system to target and eliminate cancer cells. The study involved a substantial cohort of patients who had previously been treated with proteasome inhibitors, immunomodulatory drugs (IMiDs), and CD38 antibodies. A significant portion of these patients were identified as triple-class refractory, with seventy-seven percent of participants resistant to these three classes of therapy, and ninety percent refractory to their most recent line of treatment.

Safety and Tolerability

A key focus of the study was the assessment of teclistamab’s safety profile. Out of 165 patients evaluated for safety, the drug was found to be well-tolerated when administered subcutaneously on a weekly basis. Notably, severe cases of cytokine release syndrome (CRS) were infrequent, with only one instance of grade three CRS reported. The onset and median duration of CRS were both approximately two days, indicating manageable side effects that would not preclude the use of teclistamab in outpatient settings.

Efficacy Outcomes

The efficacy of teclistamab in this heavily pretreated patient population was notably high, with an overall response rate of sixty-two percent. This included twenty-nine percent of patients achieving a complete response, demonstrating the drug’s potential to elicit significant anti-myeloma activity. The durability of these responses was also promising, as the median duration of response had not been reached by the time of data presentation. Early progression-free survival (PFS) data suggested encouraging outcomes, with six and nine-month PFS rates of sixty-four and fifty-eight percent, respectively.

Future Directions and Clinical Implications

The study’s results have sparked discussions about the broader applicability of teclistamab in the treatment spectrum of multiple myeloma. Given its efficacy and safety profile, there is optimism about its potential approval by regulatory authorities such as the FDA and EMA. The convenience of its subcutaneous administration and its status as an “off-the-shelf” therapy make it an attractive option for patients with advanced disease. Additionally, ongoing trials are exploring the possibility of combining teclistamab with other therapeutic agents, including daratumumab and more conventional treatments, to enhance its efficacy.

Philippe Moreau, MD Interview Conclusion

The phase 1/2 study of teclistamab represents a significant step forward in the treatment of relapsed and refractory multiple myeloma. Its promising safety and efficacy profile suggest that it could soon become a valuable addition to the arsenal against this disease, potentially benefiting patients who have exhausted other treatment options. As the medical community awaits the publication of these results in a peer-reviewed journal and the subsequent review by regulatory bodies, there is cautious optimism that teclistamab will be available for clinical use in the near future. Moreover, the development of teclistamab and other bispecific antibodies targeting various antigens heralds a new era in the management of multiple myeloma, offering hope for improved patient outcomes.

Teclistamab (TECVAYLI®) Outpatient Admin in Multiple Myeloma from ASH 2023 – Robert Rifkin, MD

At the ASH 2023 conference, Dr. Robert Rifkin, a renowned medical oncologist and hematologist from the Rocky Mountain Cancer Centers and a member of the U.S. Oncology Network, shared insights into a pioneering phase two study focused on the outpatient administration of Teclistamab (TECVAYLI®), a BCMA-targeting bispecific antibody designed for patients with multiple myeloma. This study represents a significant departure from traditional treatment modalities, aiming to introduce new classes of myeloma drugs into the clinical and community settings in a more patient-friendly manner.

Teclistamab (TECVAYLI®), being the first bispecific antibody approved for multiple myeloma, presented unique administration challenges, including a requirement for step-up dosing and hospitalization to monitor potential toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS). Dr. Rifkin highlighted the logistical challenges of hospitalization, including bed availability and the convenience and caregiver issues it presents.

Preemptive Management of CRS in Multiple Myeloma Treatment: Enhancing Outpatient Care with Teclistamab

The phase two study aims to preemptively address cytokine release syndrome by administering tocilizumab and steroids before Teclistamab (TECVAYLI®). Preliminary data suggests this approach could significantly reduce the incidence of CRS, making treatment more convenient and keeping patients out of the hospital. This is crucial in today’s healthcare landscape, where hospital resources are stretched thin, and staff turnover necessitates constant retraining on managing the unique toxicities associated with bispecific antibodies and CAR T-cell therapies.

Dr. Rifkin elaborated on the study’s rationale, emphasizing the need for continuous therapy in managing multiple myeloma, a disease that, to date, remains incurable. The study focuses on patients who have undergone four prior lines of therapy and are refractory to multiple drugs, introducing them to a new class of treatment that has shown remarkable activity. The goal is to manage initial toxicity effectively so that patients can return to their referring providers for ongoing treatment, making the process more efficient for all involved.

Safety is a paramount concern in this study, with extensive patient monitoring and management strategies in place to ensure adverse events are promptly addressed. Patients and their caregivers are educated on monitoring their health signs at home, and emergency protocols are established to ensure quick and effective treatment for CRS or any other complications.

The MAJESTIC-I study: The Impact of Outpatient Teclistamab Treatment

The MAJESTIC-I study, which laid the groundwork for this approach by demonstrating a reduction in CRS incidence with preemptive tocilizumab administration, underscores the potential of outpatient administration of Teclistamab (TECVAYLI®) to revolutionize treatment for patients with relapsed refractory multiple myeloma. Dr. Rifkin’s study builds on this foundation, seeking to validate a safe, effective outpatient treatment model that could significantly impact clinical practice.

By focusing on making bispecific antibody therapy more accessible and manageable in community settings, this study addresses a critical need for practical and convenient treatment options. The evolution of myeloma treatment, from lengthy IV infusions to more manageable subcutaneous administrations, reflects the broader trend toward improving patient experience and outcomes.

Dr. Rifkin’s insights at ASH 2023 offer a glimpse into the future of multiple myeloma treatment, where innovations in drug administration and management of side effects could make powerful therapies like Teclistamab (TECVAYLI®) accessible to a broader patient population. As the study progresses, it promises to contribute valuable knowledge to the field, potentially transforming how clinicians approach the treatment of this challenging disease.

Teclistamab (TECVAYLI®) Toxicity and Efficacy Outcomes in Multiple Myeloma Above 70 [ASH 2023] – Hamza Hashmi, MD

At ASH 2023, the spotlight was on Dr. Hamza Hashmi, a distinguished hematologist from Charleston, South Carolina, affiliated with MUSC Health University Medical Center, as he delved into the outcomes of Teclistamab (TECVAYLI®) treatment in patients over 70 with relapsed refractory multiple myeloma. This multicenter study provided crucial insights into the toxicity and efficacy of this BCMA-directed bispecific T-cell engager in an older patient cohort, challenging prevailing notions about age as a barrier to advanced therapies.

Teclistamab (TECVAYLI®) has emerged as hope for patients with relapsed refractory multiple myeloma

Teclistamab (TECVAYLI®) has emerged as a beacon of hope for patients with relapsed refractory multiple myeloma, a group that has historically faced limited treatment options. Dr. Hashmi’s study analyzed nearly a hundred patients, focusing on those aged above 70, who often present with complex medical profiles including compromised physical performance, organ dysfunction, and high-risk disease features. Despite these challenges, the study revealed that older patients experienced similar safety and efficacy outcomes compared to their younger counterparts, with the exception of a higher incidence of grade three and four thrombocytopenia.

Age-Based Treatment Criteria: The Efficacy of Teclistamab in Older Multiple Myeloma Patients

This finding is particularly significant as it underscores the importance of not letting age alone dictate eligibility for potentially life-saving T-cell engaging therapies. The real-world analysis conducted by Dr. Hashmi and his team showed that older patients with relapsed refractory multiple myeloma treated with Teclistamab (TECVAYLI®) could achieve comparable response rates and progression-free survival as younger patients. Such results could profoundly influence treatment decisions, affirming Teclistamab (TECVAYLI®) as a viable option for older patients and encouraging a reevaluation of age-based treatment criteria in community practice.

Managing Adverse Effects and Infection Risks in Teclistamab Treatment for the Elderly

However, the higher incidence of severe thrombocytopenia within the first 90 days of treatment in older patients warrants a careful approach. Dr. Hashmi attributed this to factors like prolonged disease duration, extensive prior treatments, and diminished bone marrow reserve in the elderly. This adverse effect, though manageable, calls for vigilant monitoring and, when necessary, interventions such as eltrombopag to support bone marrow hematopoiesis and caution with anticoagulation or antiplatelet therapy.

Regarding infection rates, the study’s findings were equally encouraging, showing no significant difference between older and younger patients. This outcome highlights the effectiveness of rigorous anti-infective prophylaxis protocols accompanying Teclistamab (TECVAYLI®) treatment, including acyclovir for HSV and VZV prophylaxis, Bactrim or Pentamidine for PJP prophylaxis, and IVIG for hypogammaglobulinemia. Such strategies are crucial for mitigating infection risks in a patient population inherently more vulnerable to infectious complications.

Dr. Hashmi’s insights from ASH 2023 illuminate the path forward for treating older patients with relapsed refractory multiple myeloma. By demonstrating that Teclistamab (TECVAYLI®) can be safely and effectively used in patients above 70, this study challenges traditional hesitations around age and treatment eligibility. It underscores the need for individualized treatment plans that consider the patient’s overall condition and potential benefits of therapy, rather than age alone.

As the medical community continues to explore and understand the nuances of treating older patients with advanced therapies, studies like Dr. Hashmi’s serve as critical guides. They not only expand our knowledge of how these treatments perform across different age groups but also advocate for a more inclusive approach to care. The findings from this study advocate for leveraging anti-infective strategies and managing adverse effects proactively, ensuring that advanced treatments like Teclistamab (TECVAYLI®) become accessible to all patients who stand to benefit, irrespective of age.

Reference Links:

TECVAYLI® (teclistamab-cqyv) biweekly dosing approved by the U.S. FDA for the treatment of patients with relapsed or refractory multiple myeloma: https://www.prnewswire.com/news-releases/tecvayli-teclistamab-cqyv-biweekly-dosing-approved-by-the-us-fda-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma-302066627.html?tc=eml_cleartime

FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma

New England Journal of Medicine: Teclistamab in Relapsed or Refractory Multiple Myeloma: https://www.nejm.org/doi/full/10.1056/NEJMoa2203478

Video Links on OncologyTube:

Updated Results from MajesTEC-1 with Philippe Moreau, MD: https://oncologytube.com/philippe-moreau-md-chunantes-ash21-majestec1-rrmm-multiplemyeloma-cancer-research-updated-results-from-majestec-1-study/

Teclistamab Outpatient Admin in Multiple Myeloma: https://oncologytube.com/teclistamab-outpatient-admin-in-multiple-myelomaae%c2%a8/

Teclistamab Toxicity and Efficacy Outcomes in MM Above 70 [ASH 2023]: https://oncologytube.com/teclistamab-toxicity-and-efficacy-outcomes-in-mm-above-70-ash-2023/