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Early teclistamab discontinuation after deep response showed PFS comparable to continuous therapy in relapsed/refractory myeloma in the LimiTEC trial.
Early discontinuation of teclistamab (Tecvayli) after 6 to 9 months of treatment was associated with comparable outcomes to continuously administered therapy with the BCMA-directed T-cell engaging bispecific antibody in patients with relapsed/refractory multiple myeloma, according to descriptive interim findings from the LimiTEC trial (NCT05932680) that were presented the 2025 ASH Annual Meeting & Exposition.1
“In this preliminary analysis, teclistamab discontinuation after 6 to 9 months in patients with very good partial response or better [≥VGPR] yielded durable responses off therapy in most patients,” Beatrice Razzo, MD, lead study author and assistant professor at Thomas Jefferson University in Philadelphia, Pennsylvania, and coauthors wrote in the poster. “Outcomes were comparable to historical expectations with continuous therapy,” Razzo added.
Teclistamab was first approved in 2022 and received supplemental approval for a reduced dosing frequency of 1.5 mg/kg every 2 weeks in patients with relapsed/refractory multiple myeloma who sustained complete response (CR) or better for 6 months or more.2 Both approvals were based on data from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098), which demonstrated that over half of patients (59.4%) achieved ≥ VGPR and that the median duration of response (DOR) exceeded 2 years (25.6 months) in this population.1 Landmark analysis also indicated that the 6- and 12-month DOR rates in this population were 76% and 65%, respectively. This same population experienced 6- and 12-month progression-free survival (PFS) rates of 77% and 64%, respectively.
Given the depth and quick onset of responses investigators theorized that fixed-duration therapy may provide comparable outcomes to that of continuous administration while limiting the risk of chronic infectious complications and improving quality of life. To that end, the prospective LimiTEC trial was initiated to evaluate teclistamab discontinuation in patients who achieved deep response.
LimiTEC was a multisite, single-arm, noninferiority trial that evaluated controlled drug discontinuation in patients who achieved ≥ VGPR after 6 to 9 months of teclistamab. Per the trial schema, patients who received a dose intensity of at least 3 mg/kg/month discontinued teclistamab with the ability to resume therapy upon disease progression or early multiple myeloma growth.
The primary end point was freedom from teclistamab failure 6 months after enrollment. Failure was defined as the time of first disease progression in patients whose disease did not response to retreatment with teclistamab.
Noninferiority could be claimed if the 6-month failure-free probability was comparable to the historical control of 79% in MajesTEC-1.
The data cutoff was November 15, 2025, for the 50 patients who were enrolled by October 15, 2025.
Baseline characteristics revealed that patients were heavily pretreated with 90% presenting with triple-class refractory disease and 22% undergoing prior treatment with BCMA-directed therapy. The median time from diagnosis was 7.1 years (range, range, 1.0-23.7).
Additional findings indicated that humoral immune reconstitution was gradual, beginning approximately 6 months after treatment discontinuation and only exceeded the serum free light chain normal range of between 5.6 and 23 mg/L 25 months after discontinuation. Moreover, the median CD19 count reached the normal range of between 110 and 660 cells/uL around 7 months and fell below the lower limit of the range around 13 months after treatment discontinuation.
With median follow-up of 12.8 months (range, 10.2-18.6) the median PFS after enrollment was 19.9 months (95% CI, 17.9-not available). The 6- and 12-month PFS rates were 76.4% (95% CI, 64.5%-90.4%) and 68.2% (95% CI, 55.2%-84.3%), respectively. The 1-year overall survival rate was 90% (95% CI, 81%-100%).
PFS outcomes were also stratified according to receipt of prior BCMA-directed therapy and depth of response by serum/urine. The 6- and 12-month PFS rates in patients who received prior BCMA-directed therapy (n = 11) were 90% (95% CI, 73%-100%) and 77% (95% CI, 53%-100%), respectively. Patients without exposure to BCMA-directed therapy (n = 39) experienced 6- and 12-month PFS rates of 72% (95% CI, 59%-90%) and 66% (95% CI, 51%-85%), respectively. Patients who achieved CR or better (n = 34) saw 6- and 12-month PFS rates of 79% (95% CI, 65%-90%) and 70% (95% CI, 55%-90%), respectively; those who achieved less than CR (n = 15) saw 6- and 12-month PFS rates of 73% (95% CI, 54%-100%) and 65% (95% CI, 44%-96%), respectively.
BCMA loss was also exhibited among patients with early progression events (n = 4 of 8). “High response rate to talquetamab further implicates target loss rather than resistance to [the] bispecific antibody mechanism as the dominant reason for teclistamab retreatment failure,” the authors noted.
A total of 17 patients experienced disease progression according to International Myeloma Working Group criteria. Fifteen restarted teclistamab at a median of 5.5 months after enrollment. None of the 12 patients who restarted within 12 months of enrollment responded and only 1 of the 3 patients who restarted at least 1 year after enrollment responded. Notably, 6 of the 7 patients who received talquetamab-tgvs (Talvey) after teclistamab retreatment responded. Four patients died, all due to disease progression.
“BCMA loss among patients with early progressive disease suggests continuous teclistamab would have yielded similar outcomes,” the authors stated. “Experience remains limited with teclistamab retreatment in patients with at least 12 months off therapy,” the authors concluded.
Disclosures: No disclosures were provided for Razzo.
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