CAR T-Cell Therapy & Tec-Dara: Which Comes First?
- Tec-Dara (teclistamab + daratumumab) is a powerful “off-the-shelf” immunotherapy given by injection. In clinical trials it produced dramatically higher response and longer remissions than older regimens at first relapse. It can often be started quickly and given in outpatient/community settings, with generally manageable side effects.
- CAR T-cell therapy offers a one-time personalized treatment that can induce very deep, durable remissions and was shown to significantly improve survival versus standard therapy. It requires specialized treatment centers, a caregiver, and close monitoring for side effects.
- Both treatments target BCMA, so doctors often prefer to give CAR T first if possible, then use a bispecific like Tec-Dara later if needed.
- However, Tec-Dara is an excellent alternative for patients who aren’t eligible for CAR T or would prefer to avoid the treatment.
“Even with newer options like Tec-Dara, if a patient can receive CAR-T, I strongly recommend CAR-T,” Dr. Ehsan Malek, a medical oncologist at Roswell Park in New York, says. “It produces a more durable response with a one-time treatment.”
Since the U.S. Food and Drug Administration’s (FDA) approval of teclistamab (Tecvayli) plus daratumumab hyaluronidase (Darzalex Faspro), often referred to as “Tec‑Dara,” clinicians have been considering the option for adults with relapsed or refractory multiple myeloma after at least one prior line of therapy. The approval reflects a broader shift towards using immune therapies earlier, when the immune system is stronger, allowing patients to more safely benefit from a potential deeper response.
There are now two very powerful, but very different, BCMA-directed approaches that can be considered as early as first relapse: CAR T‑cell therapy and Tec‑Dara. When it comes to sequencing, however, CAR T-cell therapy still tends to be the first choice when possible.
“If a patient can go to CAR T, I strongly suggest CAR T. If not, Tec‑Dara may be an option,” Dr. Malek tells SurvivorNet Connect. This is because CAR T is typically a single infusion designed to create a long treatment‑free stretch, while Tec‑Dara is a therapy patients stay on continuously as long as it’s working and tolerable.
Why CAR T Still Comes First
At first relapse, patients are often fitter than they will be later, their T cells may be healthier, and they may have more time and resilience to handle an intense treatment that requires a specialized center such as CAR T-cell therapy.
Still, the choice between CAR T and Tec-Dar is not always clear-cut. In practice, the conversation about “best sequence” often starts with a simple, pragmatic question: “Can this patient get CAR T?” The question is a reflection of the many factors that still influence the availability of CAR T, such as the patient’s ability to travel and access a caregiver, scheduling, cost, and wait time.
Prior therapies a patient received also play a role. If they relapsed while taking daratumumab (for example, during daratumumab‑based maintenance), some teams will caution that Tec‑Dara’s results in trials may not translate as cleanly, because the pivotal MajesTEC‑3 trial excluded patients with disease refractory to anti‑CD38 antibodies.
It’s also important to make patients aware that despite its potential to induce a long, chemo-free remission with a single infusion, standard preparation for CAR T-cell therapy includes a regimen of lymphodepleting chemo, such as cyclophosphamide and fludarabine. It also requires specialized monitoring for CRS and neurologic toxicities, and has updates for rare, serious late toxicities such as immune effector cell-associated enterocolitis.
Where Tec‑Dara Fits In Today
Despite CAR T still being choice No. 1 at relpase, Tec‑Dara is a potent immune therapy that can be started without the delays associated with CAR T logistics.
Teclistamab is an “off the shelf” option, but it does require step‑up dosing with close monitoring to reduce the risk of cytokine release syndrome (CRS) and neurologic toxicity.
“The trade-off with the Tec-Dara approach is you have to stay with continuous therapy,” Dr. Malek says. “You have to stay on Tec-Dara for as long as you benefit. CAR T-cell, that is a one-time therapy and no chemotherapy after that.”
Current labeling instructions include hospitalization for 48 hours after step‑up doses and guidance to remain near a healthcare facility with monitoring after the first full treatment dose.
Infection prevention is also a central part of care. Trial data show that teclistamab can cause infections and low immunoglobulin levels. Proactive discussions on antiviral prophylaxis, vaccines (when appropriate), and whether IVIG might be needed should be taken before the treatment begins.
The biggest “sequencing” nuance with Tec‑Dara is that it may look most impressive in patients who are daratumumab‑naïve or still daratumumab‑sensitive, and less dramatic in patients whose myeloma is actively progressing on anti‑CD38 therapy. Doctors increasingly name that upfront so patients don’t feel misled by headline trial numbers.
‘Switching The Target’
A newer sequencing principle is “switch the target if you can.” If a patient relapses after BCMA‑targeted therapy (either BCMA CAR T or a BCMA bispecific like teclistamab), many myeloma programs aim to move to an immunotherapy targeting a different target, such as GPRC5D, rather than repeating another BCMA‑directed strategy right away.
This is partly about biology (antigen loss or reduced BCMA expression can contribute to resistance) and partly about ensuring the patient experiences CAR T‑level toxicity only when the potential benefit is high.
“When we come to day-to-day practice, theoretical background is mostly what kind of patients is in front of me. If a patient can go to CAR T-cell, I strongly suggest CAR T-cell,” Dr. Malek says. “Another point is also very important: nowadays around 20-30% of patients before being eligible for Tec-Dara, they are part of the Darzalex maintenance program and they are on Darzalex already or Daratumumab anti CD-38 when they relapse, therefore they are not meeting eligibility criteria for Tec-Dara.”
