Evaluating T-Cell Therapies in First-Line Multiple Myeloma Treatment

There are limited randomized data on studies that focus on T-cell–directed therapies in the first-line setting for multiple myeloma. However, the ongoing CARTITUDE-5 and CARTITUDE-6 studies are comparing chimeric antigen receptor (CAR) T-cell therapies with traditional treatments, said Rahul Banerjee, MD, FACP, assistant professor for the Division of Hematology and Oncology at the University of Washington.

Banerjee attended the annual International Myeloma Society conference to discuss how to determine the type of T-cell–directed therapies to use for patient populations. Although newer CAR T-cell therapies are expected to be more effective based on less T-cell exhaustion, he expressed concerns regarding infectious complications and the unmet need for specialized centers that are equipped to treat CAR T-cell therapies.

The CARTITUDE-5 study is comparing the efficacy of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) induction followed by a single administration of ciltacabtagene autoleucel (cilta-cel) vs VRd induction followed by lenalidomide and dexamethasone maintenance in newly diagnosed patients with multiple myeloma.

Banerjee also addressed the CARTITUDE-6 study that is comparing the efficacy of daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) followed by cilta-cel vs DVRd followed by autologous stem cell transplant in newly diagnosed patients with multiple myeloma.

"Bispecifics are also being explored in the front-line setting. There are several studies that have been looking at this; MajesTEC-7 comes to mind."

Banerjee explains the purpose of MajesTEC-7 was to compare the efficacy of teclistamab in combination with daratumumab and lenalidomide and talquetamab in combination with daratumumab and lenalidomide vs daratumumab, lenalidomide, and dexamethasone.

Additionally, he mentions the MAIA study as an example where bispecifics were explored in a front-line setting. Banerjee states that although the study results thus far have shown some success, the risk of infections was found to be greater than he would like them to be, and he suggests the safety profiles of the drugs should be examined further.

"Even if tomorrow, teclistamab were to be approved for front-line therapy in any subset of patients, I would hazard a guess that 90% of Americans do not live within 30 minutes of a bispecific-capable center."

Banerjee concludes the interview by recognizing the specific outpatient dosing they have access to but how this falls short on a global scale.

"I do want to put a very clear note of caution there that we need to look before we leap into this world of BCMA [B-cell maturation antigen] as front-line therapy."