Tec-Dara vs. CAR T-Cell Therapy: Sequencing BCMA-Directed Therapy in Multiple Myeloma

Two pivotal phase 3 trials, MAJESTEC-3 evaluating teclistamab plus daratumumab (Tec-Dara) and CARTITUDE-3 evaluating BCMA-directed CAR T-cell therapy, have accelerated the shift of immunotherapy into the second-line setting for multiple myeloma.

As these approaches move earlier in the disease course, clinicians increasingly must decide how Tec-Dara and CAR T should be sequenced to maximize patient outcomes. A prevailing approach among some myeloma specialists is to prioritize CAR T therapy in eligible patients at first relapse.

However, other factors must be considered, including patient preference, Dr. Al-Ola Abdallah, director of the Plasma Cell Disorder Program at the University of Kansas Medical Center, tells SurvivorNet Connect.

“We always have to consider the patient’s goals and timing,” Dr. Abdallah explains. “Some patients want to delay CAR T because of travel, family events, or other commitments. In those cases, bispecific therapy provides an effective and flexible alternative.”

Conversely, patients seeking a time-limited therapy with the potential for prolonged remission may favor CAR T.

Tec-Dara: Redefining First Relapse

Teclistamab, a BCMA-directed bispecific antibody, leverages dual immune-mediated mechanisms through T-cell engagement and antibody dependent cytotoxicity when combined with daratumumab.

In MAJESTEC-3, this combination demonstrated superior overall response rates and progression-free survival (PFS) compared with standard of care regimens in early relapsed disease. Importantly, the depth and durability of response suggest that bispecific-based combinations may redefine expectations in the first-relapse setting.

“This is a very important change in our myeloma world … the difference in progression-free survival was substantial, and it opens the door to potentially moving these therapies even earlier,” Dr. Abdallah says.

CAR T-Cell Therapy: Deep, Durable Responses

In parallel, CAR T-cell therapy, particularly the BCMA-directed ciltacabtagene autoleucel studied in CARTITUDE-3, has shown remarkable efficacy when deployed earlier in the disease course.

CAR T offers a fundamentally different therapeutic paradigm: a one time, personalized cellular therapy capable of inducing deep and sustained remissions, often accompanied by high rates of MRD negativity.

In CARTITUDE-3, early use of CAR T significantly improved outcomes compared with standard regimens, reinforcing the concept that earlier intervention with cellular therapy may yield more durable disease control.

However, Dr. Abdallah notes that “CARTITUDE-3 compared CAR T to standard of care regimens, not to bispecific therapies,” underscoring the absence of direct comparative data between these two immunotherapy approaches.

Real-World Sequencing is Taking Shape

Despite the lack of head-to-head trials, clinicians are actively developing sequencing strategies based on biological rationale, logistics, and real-world experience. A prevailing approach among some myeloma specialists is to prioritize CAR T therapy in eligible patients at first relapse, according to Dr. Abdallah.

“If the patient is eligible for CAR T, I usually consider it as the first option,” he explains. “It is a one-time treatment, and if patients remain in remission for a couple of years, they can later receive bispecific therapy and still derive benefit.”

This strategy is further supported by the observation that T-cell fitness is optimal earlier in the disease course.

“The T cells we collect earlier are healthier and more potent, which likely contributes to better outcomes with CAR T,” Dr. Abdallah adds.

Antigen Targeting & Resistance: The BCMA Challenge

Equally important is the issue of antigen targeting and resistance. Both CAR T and teclistamab rely on BCMA expression, raising concerns about sequencing.

“Continuous exposure to BCMA-directed bispecific therapy may exhaust the target. If you use a bispecific first, the response to a subsequent BCMA CAR T may be limited because the target is no longer there or is significantly reduced,” Dr. Abdallah says.

In contrast, administering CAR T first may preserve BCMA expression at relapse, allowing for more effective use of bispecific therapy later.

“The goal is to maximize the benefit of each treatment, not to compromise one by using another too early,” he notes.

Access & Tolerability: Tec-Dara Fits Many Patients

Tec-Dara remains an important and highly effective option, particularly for patients who are not candidates for CAR T-cell therapy.

Barriers to CAR T remain for many patients. These include:

• The need for a caregiver
• Specialized centers may be far away
• Manufacturing delays
• Strict eligibility criteria related to organ function and performance status

“There are many patients who are not eligible for CAR T, whether due to comorbidities, lack of caregiver support, or logistical challenges,” Dr. Abdallah says. “In these cases, teclistamab with daratumumab is an excellent option that can be delivered off-the-shelf and often in the outpatient setting.”

Tolerability is also a major draw. “Most cytokine release syndrome is low grade, and neurotoxicity is relatively rare compared to CAR T,” Dr. Abdallah says.

Patient Preference & Real-World Logistics

Patient preference and real-world logistics are also central to decision-making. Some patients may choose to defer CAR-T due to the intensity of therapy or life circumstances.

Looking ahead, sequencing strategies will continue to evolve as more data emerge, including trials comparing immunotherapy approaches and studies targeting alternative antigens such as GPRC5D.

“We still need clinical trials to guide us, especially in patients who relapse after BCMA-directed therapies. There is an unmet need, and we must continue to innovate,” Dr. Abdallah says.

For now, a practical framework is taking shape:

1. Prioritize CAR T in eligible patients at first relapse to leverage its one-time administration and durable efficacy.
2. Reserve Tec-Dara as a highly effective, accessible option for those ineligible for CAR T or as a subsequent therapy.

“Sequencing is critical,” Dr. Abdallah adds. “We are not just choosing treatments, we are planning the entire course of disease to keep patients in remission as long as possible.”

In an era of rapidly expanding immunotherapy options, the challenge is no longer a lack of effective treatments but how to use them optimally. Thoughtful sequencing, grounded in biology, clinical evidence, and patient-centered care will be essential to achieving deeper remissions, longer survival, and ultimately, the possibility of cure in multiple myeloma.