SUMMARY

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Tumor lysis syndrome (TLS) has been reported as an adverse event in the MajesTEC-1 study.¹ The content herein is limited to available information in the published literature and the MajesTEC-1 study.
• MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^2-5
  • Cohort A (triple class exposed) included 165 patients with RRMM who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.^2,3
    • At a median follow up of 7.2 months (range, 0.3-18.0), TLS (serious, grade 3; judged by the investigator to be very likely related to TECVAYLI) was reported in 1 patient (0.6%).¹
  • Please see below for a summary of mitigation and management strategies from the MajesTEC-1 study protocol related to TLS.³
• Routine pharmacovigilance surveillance activities in Johnson and Johnson (J&J) are in place to detect safety signals, both clinical and spontaneous events as a standard part of our processes. Confirmed signals are communicated as appropriate with health authorities and investigators/healthcare professionals (HCPs) in a timely manner. As such, all reported events of TLS will continue to be monitored.

background

• Tumor lysis syndrome (TLS) is an acute, life-threatening condition that has been associated with the initiation of cytoreductive therapy for the treatment of malignancy.⁶
• In tumors which proliferate rapidly, have a relatively large tumor burden, and are highly sensitive to cytotoxic agents, the initiation of therapy can often result in the rapid release of intracellular anions, cations and the metabolic products of proteins and nucleic acids into the systemic circulation.⁷
• Clinical presentation of TLS includes hyperkalemia, hyperphosphatemia, hyperuricemia and hypocalcemia, all of which can lead to cardiac arrythmias, seizures, renal failure, and sudden death.⁸
• The Cairo-Bishop diagnostic criteria are used to classify TLS⁷:
  • Laboratory tumor lysis syndrome (LTLS): defined as either a 25% change or level above or below normal, for any 2 or more serum values of uric acid, potassium, phosphate, and calcium within 3 days before or 7 days after the initiation of chemotherapy.
  • Clinical tumor lysis syndrome (CTLS): assumes the laboratory evidence of metabolic changes and significant clinical toxicity that requires clinical intervention. CTLS is defined as the presence of LTLS and any one or more of the following criteria: creatinine ≥1.5 times upper limit of normal (ULN; age >12 years or age adjusted), cardiac arrhythmia/sudden death or seizure (none of which are directly or probably attributable to a therapeutic agent).
  • The severity is graded from 0 to 5.

Clinical data - majestic-1 study

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^2-5

Study Design/Methods

The main objectives are as follows: Part 1 (dose escalation) to determine the recommended phase 2 dose (RP2D) for TECVAYLI; Part 2 (dose expansion) to distinguish safety and tolerability of TECVAYLI at the RP2D; Part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^2,3

• Key eligibility criteria for Cohort A: ≥3 prior lines of therapy including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, no prior B-cell maturation antigen (BCMA)-targeted therapy use.²
• Primary endpoint for Cohort A: overall response rate (ORR).²
• Dosing for Cohort A:
  • Step-up doses of TECVAYLI (0.06 mg/kg and 0.3 mg/kg SC) followed by first treatment dose of TECVAYLI 1.5 mg/kg SC.²
  • Subsequent treatment doses: TECVAYLI 1.5 mg/kg SC QW until progressive disease or unacceptable toxicity.²

Results

Treatment Disposition

• At a median follow-up of 7.2 months (range, 0.3-18.0), 165 patients treated with TECVAYLI at the RP2D were included in this analysis.¹
• Patients received a median of 5 prior lines of therapy (range, 2-14).¹

Safety

• TLS was reported in 1 patient (0.6%) as serious, grade 3 (judged by the investigator to be very likely related to TECVAYLI). The patient had no clinical symptoms and TLS was diagnosed by the site based on elevated uric acid results only (potassium and phosphate levels were normal).¹
• The event lasted for 7 days and resolved; treatment with TECVAYLI was not modified.¹

MajesTEC-1 Study Protocol - Potential Risks Associated with TECVAYLI and Mitigation Strategies Related to TLS

Per protocol, potential safety risks and mitigation strategies are outlined below³:

• Frequent monitoring of chemistry parameters.
• Early recognition of signs and symptoms.
• Initiation of preventive measures in high-risk patients prior to treatment, as well as the prompt initiation of supportive care for patients who developed acute TLS during treatment as outlined by institutional guidelines.

MajesTEC-1 Study Protocol - Management of TLS

Per protocol, management guidelines are summarized below³:

• Patients should be monitored for evidence of TLS.
• Management of TLS including forced diuresis and correction of electrolyte disturbances such as hyperkalemia, hyperuricemia, and hypocalcemia, was highly recommended.
• It was also recommended that high-risk patients (ie, those with a high tumor burden [a patient with ≥60% plasma cell infiltrate on the bone marrow biopsy or aspirate, whichever is higher, or a patient with multiple extramedullary disease sites or plasmacytomas]), be treated prophylactically in accordance with local standards (eg, hydration, diuretics, allopurinol 300 mg daily and medication to increase urate excretion).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 24 June 2024.