SUMMARY

• Please refer to the local labeling for relevant information on use in renal impairment.
• MajesTEC-1 (MMY1001) is an ongoing, phase 1/2, multicohort study evaluating the efficacy and safety of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM). 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.^1,2
  • Per protocol, patients enrolled in the study were required to have adequate renal function during the screening phase described as: serum creatinine ≤1.5 mg/dL or creatinine clearance ≥40 mL/min/1.73 m² or estimated glomerular filtration rate (eGFR) ≥40 mL/min/1.73 m² based upon Modified Diet in Renal Disease (MDRD) formula calculation.²
• Lebreton et al (2024)³ published a retrospective analysis describing the safety and efficacy of TECVAYLI in 15 patients with RRMM on dialysis treated in France through an early access program.
• Khouderchah et al (2024)⁴ published a case series describing the clinical course and outcomes in 4 patients with RRMM on hemodialysis (HD) who were treated with TECVAYLI.
• Joiner et al (2023)⁵ published a case series of preliminary observations of 7 patients with multiple myeloma (MM) and severely impaired renal function treated with TECVAYLI.

product labeling

There were no clinically significant differences in the pharmacokinetics of teclistamab-cqyv based on mild or moderate renal impairment (eGFR by MDRD method: 30 to 89 mL/min). The effects of severe renal impairment (eGFR less than 30 mL/min) on the pharmacokinetics of teclistamab-cqyv is unknown.⁶

retrospective study

Lebreton et al (2024)³ published a retrospective analysis describing the safety and efficacy of TECVAYLI in 15 patients with RRMM on dialysis treated in France through an early access program.

Methods

• Patients with RRMM and end-stage renal failure treated with TECVAYLI were included in the study, which was submitted to the French Health Data Hub.
• TECVAYLI was administered subcutaneously (SC) once weekly at a dose of 1.5 mg/kg, following step-up doses of 0.06 mg/kg and 0.3 mg/kg.
• Premedication (including dexamethasone) was administered prior to TECVAYLI per European Medicines Agency (EMA) approved prescribing information.
• TECVAYLI was usually injected after dialysis, but schedules varied based on the dialysis schedule of each patient.

Results

Patient Demographics

• Data was collected from 15 patients treated with TECVAYLI in French hospitals between November 2022 and October 2023. All patients were ineligible for open clinical trials.
• Median follow up was 166 days (range, 10-315).
• Median number of previous lines of therapy (LOT) was 4 (range, 3-6).
• Median age of patients was 68 years (range, 58-83).
• Median time since diagnosis was 6 years (range, 2-9).
• Most patients had myeloma-related end-stage renal failure.
• Seven of 10 evaluable patients were considered as high-risk based on cytogenetics.

Dosing and Time to Dialysis

• TECVAYLI step-up dose 2 was administered after a median of 3 days (range, 2-7) and the first treatment dose was administered after a median of 7 days (range, 4-14).
• TECVAYLI was administered just after dialysis in 9 patients and on non-dialysis days in 3 patients.
• All patients received HD, except for 1 patient who received peritoneal dialysis.
• Dialysis was discontinued in 1 patient due to improved renal function.
• TECVAYLI dosing was reduced to once every 2 weeks (Q2W) for 5 patients, once every 3 weeks for 1 patient and once every 4 weeks (Q4W) for 1 patient.

Safety

CRS and ICANS

• Cytokine release syndrome (CRS) of grade 1/2 occurring in 11 patients (all during the step-up dosing schedule) was treated with tocilizumab (4 patients) and dexamethasone (1 patient). Grade 3/4 CRS was not reported.
• Grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred concurrently with grade 2 CRS in 1 patient, both of which were resolved following treatment with 2 doses of dexamethasone.

Infections

• Grade ≥2 infections were reported in 9 patients (grade 2, n=2; grade 3, n=4; grade 4, n=1; grade 5, n=2)
  • Bacteremia was reported in 7 patients (2 of which were fatal).
  • Viral infection was reported in 2 patients.
• Prophylaxis for infections included sulfamethoxazole-trimethoprim and valaciclovir in 12 patients and oracillin in 6 patients.
• Primary prophylaxis with SC or intravenous (IV) polyvalent immunoglobulin G (IgG) was administered to 8 patients.
• Grade 3 coronavirus disease 2019 (COVID-19) was reported in 1 patient.

Efficacy

• Median time to best response was 40 days (range, 6-124).
• A total of 14 patients achieved a response. Of these, 2 patients experienced stringent complete response (sCR), 2 patients experienced complete response (CR), 7 patients had very good partial response (VGPR) and 2 patients had partial response (PR).
• One patient with progressive disease had extramedullary disease and died from sepsis.
• One patient was not evaluable for response.
• Median progression-free survival has not been reached.

CASE SERIES

Khouderchah et al (2024)⁴ published a case series that described the clinical course and outcomes in 4 patients with RRMM who were treated with TECVAYLI. These 4 patients had end-stage renal disease (ESRD) and were on HD at the time of TECVAYLI initiation.

Patient 1

• A 65 year old female diagnosed with kappa free light chain (FLC) MM with high risk-cytogenetics developed progressive myeloma-related renal impairment and was started on HD. After treatment with 11 prior LOT, the patient was started on TECVAYLI.
• The patient was hospitalized and received 2 step-up doses of SC TECVAYLI on days 1 and 4 (0.06 mg/kg and 0.3 mg/kg, respectively), followed by the first full dose on day 7 (1.5 mg/kg).
• HD was continued irrespective of TECVAYLI administration. The patient had an incomplete HD run on day 1, and then underwent 3-hour HD runs on days 2, 5, and 7, including a HD session just prior to TECVAYLI administration on day 7. An additional HD session occurred on day 9.
• The patient had no evidence of CRS and ICANS; she was discharged 48 hours after the first full dose of TECVAYLI.
• The patient was continued on weekly TECVAYLI. Prior to the start of cycle 3, she exhibited progressive disease (per International Myeloma Working Group [IMWG] response criteria) and enlargement of a known plasmacytoma on the forehead (as seen on imaging). TECVAYLI was discontinued.

Patient 2

• A 68 year old male diagnosed with IgA kappa light chain MM with high-risk cytogenetics had ESRD from MM requiring chronic HD and chronic anemia requiring weekly red blood cell (RBC) transfusions. After treatment with 6 prior LOT, the patient was started on TECVAYLI.
• The patient was hospitalized and received 2 step-up doses of SC TECVAYLI on days 1 and 3 (0.06 mg/kg and 0.3 mg/kg, respectively), followed by the first full dose on day 5 (1.5 mg/kg SC). He received HD and 2 units of packed RBCs prior to step-up dose 1 with subsequent HD on days 7, 11, 13 and 15. Ultrafiltration was only performed on days 8 and 9.
• The patient had no clinical evidence of CRS or ICANS.
• The patient had orthopnea and shortness of breath with exertion before initiating TECVAYLI therapy. On day 6, he developed worsening orthopnea and was found to have newly diagnosed dilated cardiomyopathy, with a left ventricular ejection fraction of 28% (previously 69% in 2017) and pulmonary hypertension.
• Over the course of several days, he received ongoing transfusion support for low hemoglobin. Based on fluid status and blood pressure, HD was modified. Symptoms of cardiomyopathy and pulmonary hypertension were thought to be unrelated to TECVAYLI. He was administered the second full-treatment dose of TECVAYLI on day 13.
• Continuous renal replacement therapy was initiated in the intensive care unit due to cardiac issues prohibiting HD.
• After receiving 2 weeks of full treatment dose TECVAYLI, the patient achieved PR (per IMWG response criteria), despite his declining clinical status. No further TECVAYLI was given. The patient transitioned to comfort care and passed away shortly after.

Patient 3

• A 65 year old male diagnosed with IgG lambda MM with high-risk cytogenetics had a history of atrial fibrillation and ESRD which required HD at the time of MM diagnosis. After treatment with 8 prior LOT, the patient was started on TECVAYLI.
• The patient was hospitalized and received SC TECVAYLI step-up dose 1 (0.06 mg/kg SC) and step-up dose 2 (0.3 mg/kg SC) administered on days 1 and 3, respectively; HD was completed the day after each dose.
• The first full-treatment dose (1.5 mg/kg SC) was completed on day 5; followed by HD the next day. No clinical CRS or ICANS occurred.
• Throughout hospitalization, the patient underwent approximately 3-hour HD sessions 3 times per week. An additional HD session was given due to contrast administration.
• The patient had a prolonged hospitalization due to atrial fibrillation, new malignant pleural effusion and the development of dysphagia which was likely due to cranial nerve involvement from plasmacytoma.
• On day 12, the patient became acutely confused, and the immune effector cell-associated encephalopathy (ICE) score decreased to 5; a neurology consult deemed this to be related to metabolic abnormalities, and TECVAYLI doses were withheld.
• Despite interventions to correct the metabolic abnormalities, the patient’s neurologic status still declined. On day 14, the ICE score decreased to 1, and dexamethasone 10 mg IV every 6 hours was started for potential grade 3 ICANS.
• An increase in C-reactive protein (CRP) was noted (baseline of 1.33 mg/dL increased to 3.78 mg/dL).
• Dexamethasone was increased to every 4 hours; anakinra 100 mg SC was administered for refractory ICANS after the patient’s neurologic status did not improve.
• The family chose to withdraw care and the patient was discharged to hospice after imaging showed persistent disease and minimal improvement in mental status was observed.

Patient 4

• A 61 year old female diagnosed with standard-risk IgG kappa MM developed renal failure secondary to disease and was started on HD. After treatment with 7 prior LOT, the patient was started on TECVAYLI.
• The patient was hospitalized and received SC TECVAYLI step-up dose 1 (0.06 mg/kg SC) and step-up dose 2 (0.3 mg/kg SC) administered on days 1 and 3, respectively, with HD performed prior to each dose.
• On day 4, the patient developed grade 1 CRS with a fever of 38°C. On day 6, ferritin levels increased to a peak of 836 ng/mL (from 745 ng/mL at baseline). CRP levels increased to a peak of 11.03 mg/dL (from 0.33 mg/dL at baseline).
• The patient was treated with acetaminophen for fever and was started on broad-spectrum antibiotics. By day 5, the fever resolved and infectious work-up was negative.
• The patient received the first full-treatment dose of SC TECVAYLI (1.5 mg/kg) after HD.
• No additional CRS or ICANS events occurred, and the patient was discharged for outpatient follow-up on day 7.
• The patient had a significant decrease in the kappa FLC (161.98 mg/dL at baseline to 2.63 mg/dL) prior to the second full-treatment dose. She was continued on weekly TECVAYLI; prior to the third full-treatment dose, the patient achieved sCR (per IMWG response criteria).
• The patient completed cycle 2 before being transitioned to dosing of Q2W per provider preference. She completed 3 cycles of TECVAYLI and was lost to follow-up.

Joiner et al (2023)⁵ published a case series which reported initial observations in 7 patients with MM and severely impaired renal function treated with TECVAYLI. This series included 4 patients with ESRD on HD therapy at the time of TECVAYLI initiation.The other 3 patients had an eGFR of 16 mL/min, 22 mL/min, and 27 mL/min, respectively.

• Risk factors of the 7 patients included: ECOG performance status 2-3, cytogenetic abnormalities, extramedullary plasmacytoma, and triple-class and penta-class refractory status.The median follow-up of these observations was 2 months (range, 1-7).
• The Food and Drug Administration (FDA) approved TECVAYLI prescribing information dosing schedule was followed for dosing cycles 1 and 2. At dosing cycle 3 the frequency was modified to Q2W for 8 doses followed by Q4W starting cycle 7 onward.
  • Infection prophylaxis (starting at onset of TECVAYLI) and monthly IV Ig (starting on the second month) was administered.
• A total of 6 patients experienced CRS (maximum CRS grade 1, n=4; grade 2, n=1; grade 3, n=1). No events of ICANS or infections have been reported at this time.
• Renal improvement was noted in 1 patient with acute renal impairment related to myeloma progression (eGFR from 27 mL/min to 56 mL/min after cycle 1).Stable renal function was maintained in 1 patient.Worsening renal function along with disease progression was observed in 1 patient.
• A total of 5 patients experienced evidence of VGPR and remain on TECVAYLI treatment to date.Two patients with extramedullary plasmacytoma experienced disease progression and discontinued TECVAYLI treatment prior to cycle 2.

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 28 November 2024.