Treating Relapsed of Refractory Multiple Myeloma
- When multiple myeloma returns or stops responding to treatment, many specialists still try to do CAR T-cell therapy first if a patient can safely and realistically receive it. This is often because CAR T is a one‑time therapy with strong evidence for deep, durable remissions.
- Tec‑Dara, or teclistamab (Tecvayli) given alongside daratumumab hyaluronidase (Darzalex Faspro), just received FDA approval for relapsed or refractory multiple myeloma as well. It is taken continuously as long as patients continue to respond.
- Doctors may use Tec-Dara when CAR T is not feasible due to logistics or other conflicts. However, it may not be effective in patients whose cancer has progressed on daratumumab‑based maintenance therapy.
- 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 that aims for a different target, such as GPRC5D, rather than repeating another BCMA‑directed strategy right away.
The U.S. Food and Drug Administration (FDA) has approved a drug called teclistamab (Tecvayli) alongside daratumumab hyaluronidase (Darzalex Faspro), often referred to as “Tec‑Dara,” for adults with relapsed or refractory multiple myeloma after at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory drug.
Read More- CAR T‑cell therapy: A one‑time, personalized cell therapy
- Tec‑Dara: An “off‑the‑shelf” injectable immunotherapy combination
Comparing CAR T-Cell Therapy & Tec-Dara
At first relapse, patients are often fitter and able to handle more strenuous treatments than they will be down the line. For this reason, many doctors suggest CAR T-cell therapy at this stage.Still, the choice between CAR T and Tec-Dar is not always clear-cut. The treatment conversation often starts with a simple question: is this patient able to get CAR T? Because CAR T-cell therapy is a specialized treatment that is not available everywhere, logistics like scheduling, cost, travel, and wait time all need to be considered.
“If a patient can go to CAR T, I strongly suggest CAR T,” Dr. Malek says. “If not, Tec‑Dara may be an option.”
CAR T-cell therapy 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.
This is also where doctors reality‑check expectations using your prior therapies. If you 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 due to the population in the clinical trial that led to the recent approval.
When Is Tec-Dara Used Today?
Doctors may reach for Tec‑Dara when they want a potent immune therapy that can be started without the delays associated with CAR T-cell therapy.
“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.”
Teclistamab requires step‑up dosing with close monitoring to reduce the risk of common immunotherapy side effects like cytokine release syndrome (CRS) and neurologic toxicity. Current U.S. labeling includes hospitalization for 48 hours after step‑up doses and instructions to remain near a healthcare facility with monitoring after the first full treatment dose.
Patients should also be aware that infection prevention becomes a central part of care. The trial that led to the approval showed that teclistamab can cause infections and low immunoglobulin levels. Proactive steps to reduce these side effects should be discussed and taken before 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 impressive headline trial numbers.
“Nowadays, around 20 to 30% of patients before being eligible for Tec-Dara, they are part of the Darzalex maintenance program … they are on Darzalex already or daratumumab anti-CD38 when they relapse,” Dr. Malek says. “Therefore, they are not meeting eligibility criteria for Tec-Dara.”
Should CAR T Still Be The First Approach?
CAR T-cell therapy remains the first choice most experts would recommend, and this is largely due to its potential to induce a long, chemo-free remission with a single infusion.
CAR T, however, is not chemo-free, and its standard preparation includes a regimen of lymphodepleting chemo, such as cyclophosphamide and fludarabine, before the CAR T-cell infusion.
It also requires specialized monitoring for CRS, neurologic toxicities, and other potential side effects.
What Happens If The Disease Returns?
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 that aims for 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.
Questions To Ask Your Doctor
- Am I eligible for CAR T right now, and if so, what would the timeline look like?
- If I relapse while receiving daratumumab, is Tec‑Dara still an option?
- Is there significant benefit to waiting for CAR T-cell therapy over starting Tec-Dara immediately?
- What will the first month of Tec‑Dara treatment actually look like (hospitalization, monitoring, etc.)?
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