TECVAYLI - Occurrence and Management of Tumor Lysis Syndrome

SUMMARY

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Tumor lysis syndrome (TLS) has been reported as an adverse event in the MajesTEC-1, MajesTEC-3, and MajesTEC-9 studies.^1-3
• Summarized below are mitigation and management strategies from the MajesTEC-1, MajesTEC-3, and MajesTEC-9 studies related to TLS.^4-6
• 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.

PRODUCT LABELING

• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

background

• TLS is an acute, life-threatening condition that has been associated with the initiation of cytoreductive therapy for the treatment of malignancy.⁷
• 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.⁸
• Clinical presentation of TLS includes hyperkalemia, hyperphosphatemia, hyperuricemia and hypocalcemia, all of which can lead to cardiac arrythmias, seizures, renal failure, and sudden death.⁹
• The Cairo-Bishop diagnostic criteria are used to classify TLS⁸:
  • 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 - majestEc-1 study

MajesTEC-1 (NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with relapsed/refractory multiple myeloma (RRMM).^4,10

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.^4,10

• Key eligibility criteria for Cohort A: ≥3 prior lines of therapy (LOTs) including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb), no prior B-cell maturation antigen (BCMA)-targeted therapy use.¹⁰

Results

Median follow-up of 7.2 months

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

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

Median follow-up of 30.4 months

Treatment Disposition

• At a median follow-up of 30.4 months (range, 0.3-41.5), 165 patients treated with TECVAYLI at the RP2D were included in this analysis.¹¹ 

Safety

• No additional events of TLS were reported.¹¹ 

Clinical data - majestEc-3 study

MajesTEC-3 is a phase 3, randomized, open-label study evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO (Tec-Dara subcutaneous [SC]) vs investigator’s choice of DARZALEX FASPRO, pomalidomide, and dexamethasone (DPd) or DARZALEX FASPRO, bortezomib, and dexamethasone (DVd) in patients with RRMM after 1-3 prior LOTs.¹² 

Study Design/Methods

• Key eligibility criteria: RRMM, 1-3 prior LOTs, including a PI and lenalidomide, patients with only 1 prior LOT must have been lenalidomide-refractory per International Myeloma Working Group criteria, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2.¹²

Results

Treatment Disposition

• At a median followup of 34.5 months, 291 patients treated with TecDara SC and 296 patients treated with DPd/DVd were included in the study.¹²

Safety

• Treatment-emergent TLS was reported for 2 participants (0.7%) in the Tec-Dara group and no participants in the control group. Neither participant discontinued study treatment due to TLS.²

Clinical data - majestEc-9 study

MajesTEC-9 is an ongoing, phase 3, randomized, open-label, multicenter study comparing TECVAYLI with investigator’s choice of pomalidomide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with RRMM who previously received 1-3 LOTs including an anti-CD38 mAb and lenalidomide.¹³

Study Design/Methods

• Key eligibility criteria: ECOG PS 0-2, 1-3 prior LOTs including antiCD38 mAb and lenalidomide, with documented disease progression or no response to last regimen, and no prior BCMAtargeted therapy, no prior pomalidomide/ineligible for bortezomib retreatment, and no prior carfilzomib exposure.¹³

Results

Treatment Disposition

• At a median follow-up of 17.3 months, 291 patients treated with TECVAYLI, and 283 patients treated with PVd/Kd were included in the analysis.¹³

Safety

• Treatment-emergent TLS was reported in 6 participants (2.1%) in the TECVAYLI group and 4 participants (1.4%) in the control group. All events in the TECVAYLI group were Grade 3 or 4. Grade 5 TLS was reported in 1 participant in the control group. No participants in the TECVAYLI group and 1 participant in the control group discontinued study treatment due to TLS.³

Clinical data - Management and Mitigation Strategies

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

Per protocol, potential safety risks and mitigation strategies are outlined below⁴:

• Frequent monitoring of chemistry parameters.
• Early identification of clinical signs and symptoms.
• Preventive measures should be initiated in patients at high risk before starting therapy.
• As specified in institutional guidelines, rapid supportive care is essential for patients who develop acute TLS during treatment.

Management of TLS - MajesTEC-1, MajesTEC-3, and MajesTEC-9 Study Protocols

Per protocol, management guidelines are summarized below^4-6:

• Monitor for TLS.
• The following management strategies were highly recommended:
  • Forced diuresis
  • Correcting electrolyte imbalances such as:
    • Hyperkalemia
    • Hyperuricemia
    • Hypocalcemia
• In accordance with local standards, the following preventive measures are recommended for patients at high-risk (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]), such as:
  • Rehydration
  • Use of diuretics
  • Daily allopurinol 300 mg
  • Medications that promote 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) was conducted on 18 June 2026.