CONFERENCE UPDATE: EHA 2025

Talquetamab + teclistamab yields deep and durable responses in EMD-positive RRMM: Results from the phase 2 RedirecTT-1 trial

HEMATOLOGY
25 Sep 2025

STUDY DESIGN

Extramedullary disease (EMD) in multiple myeloma (MM) is associated with a poor prognosis, with patients being approximately 87% less likely to respond to standard treatments compared to those without EMD.1 Previous pivotal studies have shown modest efficacy of monotherapy bispecific antibody (BsAb) in this setting, where patients with EMD treated with talquetamab (antiGPRC5D) and teclistamab (antiBCMA) monotherapies have both exhibited overall response rates (ORR) of approximately 43%.1

Building on preliminary data from the RedirecTT-1 phase 1 trial, the phase 2 RedirecTT-1 trial enrolled patients aged ≥18 years with measurable MM with true EMD, defined as ≥1 non-radiated bone-independent soft tissue plasmacytoma ≥2cm in greatest dimension as confirmed by central review of positron emission tomography–computed tomography (PET-CT) scans.1 Patients with triple-class-exposed relapsed/refractory MM (RRMM) were included.1 Prior CAR-T or BsAb therapy (not targeted at GPRC5D or BCMA) and those with non-secretory or oligosecretory disease were permitted.1 Participants received maintenance therapy with talquetamab (0.8mg/kg) + teclistamab (3.0mg/kg), administered subcutaneously every two weeks, following a step-up dosing regimen, and continued until disease progression.1

A total of 90 patients were enrolled.1 Of these, 39% had non-secretory/oligosecretory disease, 20% had received prior anti-BCMA CAR-T therapy, and 9% had prior BsAb exposure.1 Notably, 84% were triple-class refractory, and 36% were penta-drug refractory, underscoring a cohort with difficult-to-treat disease.1 The median follow-up duration was 12.6 months.1

The primary endpoint was the overall response rate (ORR) determined based on EMD response assessed by central radiology review of whole-body PET-CT scans.1 The secondary endpoints presented included time to response, duration of response (DOR), median progression-free survival (mPFS), and overall survival (OS).1

FINDINGS

 
  • The primary endpoint was ORR determined based on EMD response assessed by central radiology review of whole-body PET-CT scans1
  • The combination of talquetamab and teclistamab demonstrated an ORR of 78.9% (95% CI: 69.0-86.8) in patients with RRMM and EMD, with over half of the patients (54.4%) achieving a complete response (CR)1
 
  • The secondary endpoints presented included time to response, DOR, mPFS, and OS1
  • The median time to first response was 2.6 months (range: 1.0-5.8), and the median time to best response was achieved at 4.7 months (range: 1.0-11.9)1
  • The mPFS was 15.4 months (95% CI: 10.8-not estimable [NE]), with 61.0% of patients estimated to remain progression-free at 1 year¹
  • Treatment responses were durable, with a median DOR of 13.8 months (95% CI: 11.5-NE) and an estimated 64.1% of patients progression-free at 12 months1
  • Median OS was not reached at time of analysis, and the 12-month OS rate was estimated at 74.5%, highlighting promising survival outcomes1
  • At data cut-off with a median follow-up of 13.4 months, 66.2% of responders remained on therapy, and 92.7% deepened or maintained their response after switching to monthly dosing after cycles 4-61
 
  • The combination of talquetamab and teclistamab showed a safety profile consistent with their individual monotherapies, with cytokine release syndrome (CRS) as the most common adverse event (AE) (77.8%) and immune effector cell-associated neurotoxicity syndrome (ICANS) reported in 12.2% of patients, including one grade 3/4 case (1.1%)1
  • Neutropenia was the most frequent grade 3/4 AE, affecting 62.2% of patients1
  • Infections were reported in 78.9% of patients, with grade 3/4 infections occurring in approximately one-third of the cohort, most of which were limited to early treatment cycles1
  • Grade 5 infections were observed in 5.6% of patients1
  • Post-treatment hypogammaglobulinemia was reported in 70.0% of patients, and 86.7% received intravenous immunoglobulin1

 

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