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Omar Nadeem, MD, Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Center for Early Detection and Interception of Blood Cancers at Dana-Farber Cancer Institute; Nausheen Ahmed, MD, a hematologist-oncologist and associate professor in the Division of Hematologic Malignancies and Cellular Therapeutics at The University of Kansas Cancer Center; and Forat G Lutfi, MD, an assistant professor in the Division of Hematologic Malignancies and Cellular Therapeutics at The University of Kansas Cancer Center, provided insights on the FDA’s decision to eliminate Risk Evaluation and Mitigation Strategies (REMS) requirements for all currently approved CD19- and BCMA-directed autologous CAR T-cell immunotherapies in hematologic malignancies.

This decision, which was announced on June 27, 2025, is expected to expand access to these therapies by reducing longstanding socioeconomic, geographic, and logistical barriers, experts explained when interviewed by OncLive®.

Watch the video or read the transcript below to learn more about how this regulatory change is expanding patient access by reducing monitoring requirements and logistical burdens, while also fostering the development of hybrid care models that integrate community oncology centers into the delivery of this curative therapy. For a more in-depth look at the factors informing the removal of this safeguard and its implications for real-world oncology practice, check out our feature article.

Nadeem: The REMS requirement is no longer there for CAR T-cell therapy, which is going to be huge. Before, that was one of the reservations patients had. They could not drive for 2 months. They needed a caregiver for [1] month. These things were real barriers [to CAR T-cell therapy]. To patients going forward with this therapy, it seems much more doable for the majority of patients and their caregivers. They can take that time to get through this, and then they can go back to their community.

Ahmed: When CAR T[-cell therapy first] emerged back in 2017, just a few centers were doing it. Now it has expanded, but we know that there’s [still] room for improvement. It’s not out there in the community. When the REMS [protocols] first came about, monitoring focused on cytokine release syndrome [CRS] and immune effector cell–associated neurotoxicity syndrome [ICANS].

Lutfi: Traditionally, REMS training is required for providers and for people who are interacting with patients, and that is a time and financial barrier. It is hard for a lot of smaller-scale centers to adopt any therapy like CAR T [when] those requirements and restrictions [are in place]. The additional monitoring time period was also quite restrictive. Most centers would keep people locally for 30 days, some a little less, but that was generally what has been done. Additionally, the driving requirements, which previously lasted 8 weeks, were also restrictive for patients and limited the ability for patients who just could not do that, whether it was getting groceries or whatever was required of them.

Ahmed: This regulatory change is a huge deal. It surprised many of us that it came so fast, and we were impressed with that. We have already started making progress toward implementing it. Patients are now able to drive after 2 weeks, as long as they are stable, and they are able to go back home as long as they are stable. We are involving our community oncologists and referring oncologists earlier, and they are willing to take it on. There is more flexibility, which we love, and the patients love it.

Lutfi: As we get more comfortable and we see all these safety parameters, the risk of truly getting high-grade CRS and ICANS after 2 weeks is quite low. Most studies show [an incidence of] less than 1% to 2% [after 2 weeks post-infusion]. As we see that things are being done more safely, we are going to keep reducing the requirements and hoops that patients and their caretakers have to jump through.

Our plan is to move step by step, starting with some of our affiliated community sites. I visit some of them, and that would allow the first rollout. What we are hoping to do is shift some of the preparation and work-up for CAR T—which usually takes weeks before infusion—into the community sites. That way, when patients need echocardiograms, imaging, or other work-up that we traditionally kept at the main campus, we can do it in the community. The infusion process will still be done at the main center.

We have been giving bispecific [antibodies] in the community for over 2 years now, and [community clinicians] are very comfortable. The patients selected for community rollout [of CAR T-cell therapy] will be lower-risk or average-risk patients. We are not saying every [patient getting] CAR T should be managed in the community. Patients with primary refractory disease or relapsed, very high–risk disease, with very high risk for toxicity and complications, should not be treated in the community. Patient selection is an important factor.

Nadeem: We are moving quickly to adopt these changes since the REMS requirements were dropped. To be honest, I do not think [toxicity management] is going to change too much, because most toxicities occur within that 2-week window [after infusion]. CRS usually occurs within a week and is typically resolved by day 14. If it is not, we keep the patient until it is resolved. The more acute neurological toxicities are also usually resolved by that time point. Delayed neurological toxicities can occur weeks to months later, so that is not affected by the monitoring window.

Nadeem: The CRS timeline is fairly reliable. We can see inflammatory markers rise, and when patients develop chills or other signs, we know CRS is coming. At that point, we typically admit them around day 7, and they may stay until day 10 or 11. That means they are in the hospital for 3 days instead of 10 days, which has made a big difference for patients.

As a result, we have had to make sure we have enough providers, lab monitoring, and nursing support. It takes a whole team effort to guide management of these toxicities. It has been very smooth, and I think it will only get better over time.

Ahmed: As referring oncologists get more comfortable with CAR T-cell therapy, they will hopefully advocate for it more, and we will likely see more patients treated with CAR T-cell therapy.

First-line sacituzumab tirumotecan (sac-TMT) plus tagitanlimab (KL-A167) showed promising efficacy and safety for patients with advanced or metastatic non–small cell lung cancer, according to results from the phase 2 OptiTROP-Lung01 trial (NCT05351788) published in Nature Medicine.

In cohort 1A (n = 40), the median best percentage change in target lesions from baseline was –30.6% (range, –91.8% to 13.0%) and –44.8% (range, –89.6% to 0%) in cohort 1B (n = 63). The confirmed overall response rate (ORR) was 40.0% (95% CI, 24.9%-56.7%) in cohort 1A and 66.7% (95% CI, 53.7%-78.0%) in arm B. The disease control rate (DCR) was 85.0% (95% CI, 70.2%-94.3%) in cohort 1A and 92.1% (95% CI, 82.4%-97.4%) in cohort 1B.

The median progression-free survival (PFS) in cohort 1A was 15.4 months (95% CI, 6.7-17.9). The 6-month PFS rate was 69.2% (95% CI, 51.2%-81.6%), and the 12-month PFS rate was 51.1% (95% CI, 33.5%-66.2%). In cohort 1B, the median PFS was not reached (95% CI, 9.6-not estimable [NE]). The 6-month PFS rate was 84.2% (95% CI, 71.8%-91.4%) and the 12-month PFS rate was 58.4% (95% CI, 44.2%-70.1%).

“In this phase 2 study, the combination of sac-TMT and tagitanlimab exhibited encouraging efficacy and a manageable safety profile in patients with advanced or metastatic NSCLC in the first-line setting,” the authors of the study wrote. “These findings provide a rationale for further investigation of sac-TMT plus immunotherapy in a broad spectrum of patients with NSCLC, as evidenced by the increasing number of phase 3 studies evaluating this combination therapy.”

A total of 103 patients were enrolled. In arms 1A and 1B, the median age was 63 years in both cohorts, most patients were male (85.0% vs 76.2%), and 72.1% vs 60.3% had a smoking history. An ECOG performance status of 1 was noted in 97.5% of patients in cohort 1A and 85.7% in cohort 1B, brain metastases were observed in 12.5% and 3.2%, liver metastases in 10.0% and 14.3%, and squamous cell carcinoma was documented in 55.0% and 46.0%.

The coprimary end points of the trial included safety and ORR. Secondary end points included PFS, duration of response, and DCR according to RECIST v1.1 criteria.

In cohort 1A, sac-TMT was given at 5 mg/kg every 3 weeks plus tagitanlimab at 1200 mg every 3 weeks in each 3-week cycle. In cohort 1B, patients were given sac-TMT at 5 mg/kg every 2 weeks plus tagitanlimab at 900 mg every 2 weeks in each 4-week cycle.

Treatment-related adverse effects (TRAEs) in cohort 1A were observed in 95.0% of patients and in 96.8% in cohort 1B. Grade 3 or higher TRAEs were noted in 42.5% of patients in cohort 1A and 58.7% in cohort 1B.

Dose reductions of sac-TMT due to TRAEs were observed in 17.5% of patients in cohort 1A and 42.9% in cohort 1B. Treatment discontinuations due to any drug were observed in 2.5% and 6.3%, and discontinuation of sac-TMT was noted in 2 patients in cohort 1B, while tagitanlimab discontinuation occurred in 2.5% in cohort 1A and 3.2% in cohort 1B.

Treatment-related serious AEs occurred in 10.0% of patients in cohort 1A and 20.6% in cohort 1B.

The most common TRAEs of grade 3 or higher in cohort 1A and 1B, respectively were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%), anemia (5.0% and 19.0%), rash (5.0% and 7.9%), stomatitis (0% and 9.5%), and drug eruption (7.5% and 0%).

Immune-related AEs (irAEs) occurred in 25.0% of patients in cohort 1A and 39.7% in cohort 1B. Grade 3 or higher irAEs were noted in 7.5% of patients in cohort 1A and 12.7% in cohort 1B, with the most common between cohorts being rash (12.5% and 14.3%), increased alanine aminotransferase (ALT) (0% and 11.1%), hypothyroidism (2.5% and 7.9%), increased aspartate aminotransferase (AST) (0% and 6.3%) and hyperthyroidism (0% and 6.3%).

Reference

Hong S, Wang Q, Cheng Y, et al. First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial. Nat Med. Published online August 19, 2025. doi:10.1038/s41591-025-03883-5

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The US could break its dependence on China for many critical minerals if metals found in the waste from existing American mines were used rather than discarded, new research has found.

The US is among a growing number of countries racing to secure more independent supplies of metals including copper, lithium and nickel — which are essential for a broad range of industries, from energy to technology and defence. 

China has invested heavily in the sector for two decades and dominates the supply chains for many critical minerals.

That dominance contributed to the Trump administration’s imposition of hefty tariffs on a range of Chinese products in a bid to encourage domestic US supply chains.

The paper, published in the journal Science on Thursday by researchers at the Colorado School of Mines, said that the US could supply most of its metals needs if it made better use of mining waste.

“The US’ vulnerable supply of critical minerals is not a function of domestic geological availability,” they said. Recovering even small quantities of the byproducts “would substantially reduce net import reliance for most critical minerals,” said the researchers. 

The waste from the 54 mining operations active in the US were likely to be rich in many of the critical minerals needed by the country’s industrial sector, they added.

Their analysis found that recovering some of the metals that occur as byproducts at active mines, combined with existing production, could be “sufficient to meet US manufacturing demand for copper, iron, molybdenum, silver, nickel, zinc and [rare earths].” 

Making better use of these waste products could prove difficult, however, since the researchers noted that “a lot more research, development and policy” was needed to make it “economically feasible”.

Other nations including Australia, Canada and the EU are also trying to wean themselves off a heavy dependency on Chinese metals with plans that include investing in domestic mining or stockpiling material.

Thursday’s analysis drew on geologic data from the US, Australian and Canadian Geological Surveys, among other sources. 

Rare earth elements, which are essential for the production of magnets, have drawn particular attention in recent months following a temporary Chinese export ban on the materials that upended the global supply chain.

Despite their name, these metals are not especially rare but are often not economic to extract, with many mined as byproducts of other minerals. 

The amount of critical minerals that currently end up as US mining waste could “exceed US imports and US manufacturing demand for most elements,” the researchers said.

For 15 elements — including rare earths, gallium and germanium — recovering less than 1 per cent of the potential byproducts found in mines across the US would be enough to replace imports, they found.

For another 11, including the battery metal lithium, recovery of between 1 and 10 per cent would be needed to replace imports, they said.

“US metal mines already have sufficient mineral endowment to substantially reduce the nation’s mineral [deficit],” they said. “Unrecovered, these byproducts contribute to the country’s growing industrial waste.”