Low-dose teclistamab in newly diagnosed multiple myeloma patients

Abstract Background: Teclistamab is a bispecific antibody targeting B-cell maturation antigen (BCMA), which has shown efficacy in the achievement of deep responses in multiple myeloma (MM). The depth of response, particularly the achievement of measurable residual disease (MRD) negativity, is associated with longer progression free-survival. Nevertheless, extended teclistamab therapy has been associated with a heightened risk of infections, motivating the investigation of shorter, less intensive treatment approaches. Moreover, lower doses of teclistamab could reduce toxicity and significantly reduce treatment costs. This study aims to assess the efficacy of low-dose teclistamab as consolidation in newly diagnosed MM. Methods A single-arm phase II study is being conducted (​​NCT06758375). Transplant eligible, treatment-naive patients (pts) receive three cycles of induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd), followed by consolidation with four weekly doses of teclistamab at 1.0 mg/kg. Pts with plasma cell leukemia were excluded. Autologous transplantation is not performed. Pts who achieve a complete response (CR) or better are evaluated for MRD using flow cytometry (sensitivity: 10^-5), one month after the last dose of teclistamab. Those with CR, MRD negativity, and standard cytogenetic risk are assigned to active surveillance. Pts with MRD positivity or high cytogenetic risk initiate maintenance therapy with bortezomib. Pts with very good partial response (VGPR) or less receive one or two additional doses of teclistamab and are re-evaluated after four weeks. Those who do not achieve CR are withdrawn from the protocol and continue with conventional management. The primary endpoint of this study is response rate after teclistamab consolidation as defined by the IMWG. Secondary endpoints included adverse events (AEs), MRD status, duration of response, and progression-free survival. AEs were graded as per the CTCAE v5; cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT criteria. Results: 11 pts have been included with a median follow-up of 4.3 months (IQR: 4.0-4.3 months). Median age was 61 years (IQR: 53-67) and 54.5% (n=6) were male. The most common subtype was IgG kappa (n=4, 36.4%), followed by IgG lambda (n=3, 27.3%). According to the R-ISS, 72.7% (n=8) were in stage II or III. Six pts had high-risk cytogenetics, of which five showed 1q21 gain. One medullary plasmacytoma and two extramedullary plasmacytomas were identified. Eleven pts have completed the three cycles of VRd. Nine out the eleven evaluable pts achieved at least a VGPR, and one patient who achieved partial response (PR). Nine pts have completed consolidation with teclistamab, with an ORR of 100%. All the assessed pts (n=8), all have achieved a MRD-negative CR. Three patients remain under active surveillance whilst six are on monotherapy maintenance. All received intravenous immunoglobulin after the first dose of teclistamab. No relapses or refractoriness were reported. All pts received ambulatory treatment and no hospitalization due to AEs was required. The most common AE was cytokine release syndrome (CRS; n=10), followed by diarrhea (n=5) and local reactions (n=3), all grade 1. One case of grade 1 ICANS was reported, which did not require tocilizumab administration. The median time to onset of CRS was 4 days (1–32), with resolution in 1 day (0.5–2). There were isolated grade 2 events (neuropathy, constipation, infection) and one case of grade 2 pneumonia at 26.5 days after therapy initiation. No grade ≥3 toxicities or permanent treatment discontinuations were observed. Conclusion: Early consolidation with low-dose teclistamab achieved high rates of complete response with negative MRD in all evaluated patients, with a manageable toxicity profile. This strategy may offer an effective and safe therapeutic approach, allowing for treatment-free periods guided by MRD and risk profile, while reducing infectious complications and associated costs.