BSH 2022 | Updated results from MajesTEC-1
Rakesh Popat, BSc, MBBS, MRCP, FRCPath, PhD, University College London Hospitals, London, UK, gives an update on the preliminary results of the Phase I/II MajesTEC-1 trial evaluating teclistamab, a bispecific T-cell engager (BiTE) targeting CD3 and BCMA in patients with relapsed/refractory (R/R) multiple myeloma treated with a median of six prior lines of therapy (NCT04557098). The study reported a response rate (RR) of over 60%, with low-grade adverse events including neutropenia, cytopenia, cytokine release syndrome (CRS), and neurotoxicity. Further results on the durability of response, progression-free survival (PFS), and overall survival (OS) are eagerly awaited. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.
Transcript (edited for clarity)
The MajesTEC-1 study was for patients with relapsed and refractory myeloma, who have been exposed to a proteasome inhibitor, an immunomodulatory agent, and a CD38 monoclonal antibody. What we are presenting is the updated results of the Phase I study using the dose at the recommended Phase II dose, from the part one and the cohort expansion at part two. 95 patients were pooled into this study and were treated with teclistamab with two initial step-up doses followed by the maximum recommended Phase II dose...
The MajesTEC-1 study was for patients with relapsed and refractory myeloma, who have been exposed to a proteasome inhibitor, an immunomodulatory agent, and a CD38 monoclonal antibody. What we are presenting is the updated results of the Phase I study using the dose at the recommended Phase II dose, from the part one and the cohort expansion at part two. 95 patients were pooled into this study and were treated with teclistamab with two initial step-up doses followed by the maximum recommended Phase II dose. Patients received treatment until disease progression or intolerance.
Overall, we are reporting a response rate of 62% and importantly, there were very high VGPR and CR rates. Now this is quite a remarkable response rate for patients who’d had a median of six prior lines. The majority of these patients were triple-class refractory, and there was a significant proportion of patients who were also penta-refractory. So this is quite a heavily pretreated population.
In terms of the adverse event profile, there was some hematological toxicity with neutropenia occurring, as well as thrombocytopenia, but this was typically low-grade and was manageable with supportive care. The main non-hematological toxicity is cytokine release syndrome, as you would expect with a bispecific T-cell engager antibody. The majority of cases with cytokine release syndrome were grade one and two. There was only one grade three event, which was fully reversible. All these events were either spontaneously resolved or were managed with tocilizumab or with corticosteroids.
In terms of neurotoxicity or ICANS, the most commonly reported event was a headache and no severe ICANS was observed. The data is still fairly immature. So we don’t have a durability of response, progression-free survival or overall survival as yet. But when you look at the swim lane plot of each individual patient as they go on, what becomes apparent is that the responses deepen as time goes on. So overall, this is the pivotal Phase I / II clinical trial of teclistamab, which is a bispecific T-cell engager targeting CD3 and BCMA for patients with relapsed/refractory multiple myeloma. The response rate is over 60%. The adverse event profile is quite manageable and appears to be quite safe, and we are hoping that these will produce some quite durable responses.
Read more...
