Teclistamab Combination Shows Consistent Safety Profile in Myeloma

Emma Searle, MBChB, PhD, MA, MRCP, FRCPath, consultant hematologist at the Christie Hospital NHS Foundation Trust, and honorary senior lecturer at the University of Manchester, discusses safety results of the MajestTEC-2 trial (NCT04722146), which combined teclistamab (Tecvayli) with daratumumab (Darzalex) and lenalidomide (Revlimid) in patients with multiple myeloma.

At the 2022 American Society of Hematology Annual Meeting and Exposition (ASH), the multicohort phase 1b MajestTEC-2 trial reported results efficacy and safety results from a cohort of 32 patients who received teclistamab plus daratumumab and lenalidomide. The patients must have received between 1 and 3 lines of prior therapy including a proteasome inhibitor and immunomodulatory drug.

Cytokine release syndrome (CRS), which is commonly associated to bispecific T-cell engagers, occurred in this patient population but there were no grade 3 or 4 incidences. Immune effector cell-associated neurotoxicity syndrome (ICANS) was not observed in this cohort. Patients received granulocyte colony-stimulating factor (G-CSF) for neutropenia, which was a grade 3 adverse event (AE) or higher in 68.8% of patients, but only 12.5% had febrile neutropenia.

Searle says that the investigators are conscious of the 90% infection rate reported in patients, with 28.1% being grade 3 or higher. These infections included COVID-19, upper respiratory tract infection, and pneumonia. One patient died due to COVID-19 and another due to sepsis-related organ failure. She says that teclistamab’s immunosuppressive effect is an important learning point going forward with the use of this agent.

TRANSCRIPTION:

0:08 | CRS is something we always worry about with the bispecific antibodies. We did see that CRS was common, but it...was all of low grade. It was all grade 1 or 2; we didn't see any cases of grade 3 or 4 CRS, and we didn't see any ICANS, which is really important as we plan on using these therapies. Neutropenia was a frequent event, and as the study went on G-CSF use was encouraged to help manage that [AE]. Fortunately, febrile neutropenia was much less common event. In the main, [neutropenia is] something we're picking up on the blood tests, but the patients were well.

0:48 | The other [AE] that I think all of us who are involved in this study are very conscious of and we need to be vigilant for as teclistamab moves forward in combination studies is infection. Ninety percent of patients experienced an infection at some point during their treatment. The majority of those infections were mild, but a third of patients had more serious infections and these infections were predominantly COVID-19, upper respiratory tract infections, and pneumonia. And sadly, we did lose 2 patients after the first 2 were treated in this cohort to infection. One death was from COVID-19, and the other for multi-organ failure from sepsis, and so that's an important learning point going forward.