Category: 3. Business

As the world decarbonizes, what happens to the coal plants left behind? Some countries are reimagining them to serve a new role in a low-carbon future.

—

For more than a century, coal powered industrial growth. Entire towns and regional economies were built around coal mines and power stations. Today, as the world shifts to clean energy and decarbonizes, many of these coal-dependent regions face economic decline. The challenge is no longer only how to close coal plants safely, but what comes next for workers, infrastructure, and local communities.

The pressure to transition away from planet-warming fossil fuels is already underway in many parts of the world. In the United States, coal capacity is down by around 60% since 2010, according to the International Energy Agency (IEA). In the European Union, countries including Germany, Spain and the Netherlands have set legally binding coal phase-out deadlines before 2030. The Global South is also facing mounting pressure to cancel new coal financing.

Without planned transition strategies, retired coal sites risk becoming abandoned industrial zones, driving job losses, population outmigration, and shrinking municipal tax bases. However, emerging techno-economic pathways show that former coal regions can be repurposed into clean energy industrial hubs, turning stranded fossil fuel assets into engines of the green economy.

The solution? There are various ways that have been employed throughout the world, some of which are discussed below.

Hidden Value of Existing Coal Infrastructure 

Coal plants exist on strategically valuable industrial land. They already have grid interconnections, transmission capacity and industrial zoning permits that make it easier for these sites to host utility-scale solar farms, wind farms, and grid-scale battery storage. 

Building new renewable energy projects typically requires lengthy approval processes and costly grid upgrades. Repurposing former coal sites avoids these barriers. This approach accelerates renewable roll-out while preserving grid reliability and local employment opportunities.In the Eastern US, for example, retired coal plant sites in Appalachia are being redeveloped into solar and battery projects, supported by the Biden administration’s flagship Inflation Reduction Act.

Coal mining leaves behind land that offers larger flat areas. Once reclaimed, this land can be suitable for solar panel assembly plants or wind turbine blade manufacturing or green hydrogen electrolysis facilities. 

Germany is a great example of this. The Ruhr region transitioned from coal mining to advanced manufacturing and clean tech research parks over two decades through coordinated industrial policy and public investment – proof that long-term planning can convert declining fossil-fuel regions into innovation centres rather than economic dead zones.

Another pathway is underground mines serving as long-term energy storage facilities. To ensure reliable power supply, grids require storage technologies capable of delivering electricity for several hours or days. Decommissioned mines offer natural cavities that can store pumped hydro energy, where water is pumped uphill using excess electricity and released to generate power when needed – or compressed-air energy storage, where air is pressurised underground and later released through turbines. Pilot projects in Spain and the UK are testing mine-based gravity and compressed-air storage.

Transition for Coal Workers

Coal workers already possess transferable skills like electrical maintenance skills, heavy machinery operation experience, and safety training. Short retraining programs can shift them into solar installation, wind turbine maintenance, and grid operations. Retraining initiatives, wage insurance programs, and regional investment funds are increasingly being adopted to support a “just transition” – a policy framework ensuring that workers and communities benefit from the shift to clean energy rather than bearing its costs alone.

Final Thoughts 

With strategic reinvestment moving forward, regions can gain new industries with higher long-term job stability and local ownership of energy assets. Community investment schemes and clean-tech innovation clusters further increase regional resilience.

The transformation is not automatic. It requires coordinated policy, public-private financing, workforce planning, and long-term political commitment. However, the examples emerging across Europe and North America demonstrate that coal’s decline does not have to mean regional decline.

As the world decarbonizes, the future of former coal regions will depend on whether governments and industry treat plant closures as endings or as opportunities to build the next generation of clean energy industrial hubs.

Photo: Tom Grundy/hongkongfp.com.

Good morning and welcome back to FirstFT Asia. In today’s newsletter:

• Chinese trading firm wins big from silver route

• Can Takaichi govern Japan on star power alone?

• Indian leaders duck Trump’s Russian oil claim

• Where to stay in Hong Kong

---

We have an exclusive story today on Chinese trading firm Zhongcai Futures, which has emerged as a big winner from the recent rout in silver.

Rare silver bear: Zhongcai has booked profits of more than Rmb3.6bn ($519mn) since Friday morning after building up short positions in silver in late January, according to FT calculations based on disclosures to the Shanghai Futures Exchange. Founded three decades ago by Bian Ximing as a manufacturer of PVC pipes before branching into futures trading, Zhongcai stands out as a rare silver bear in mainland China, even as a blistering rally in the metal gathered pace through January.

Why it matters: Zhongcai’s profits highlight the recent wild volatility in precious metals trading, particularly in China, where regulators have been working to tamp down on speculative activity. It also underscores how the centre of gravity for gold and silver trading is gradually shifting towards Asia, where a frenzy of retail investment in bullion was central to driving January’s historic price surge.

Read more about Zhongcai’s aggressive bets.

Here’s what else we’re keeping tabs on today:

• Economic data: January inflation data is due from Thailand, Taiwan and the Philippines. Indonesia reports fourth-quarter GDP and Singapore publishes December retail sales.

• Results: Sony, Tata Motors, Nippon Steel, Amazon and Shell report earnings.

• Ask an Expert Q&A: Are US markets and the economy as strong as Trump claims? Take part in a live Q&A today with US managing editor Brooke Masters and financial commentator Robert Armstrong.

Five more top stories

1. Donald Trump said he had spoken to Xi Jinping about the Ukraine war, Taiwan and other issues, in a call that came two months before the Chinese leader is expected to welcome the US president on a state visit in Beijing. The call took place after Xi spoke to Russia’s President Vladimir Putin, according to Chinese state media.

• More US-China news: Nvidia’s sales of H200 AI chips to China are still awaiting final approval from Washington as the US government conducts a national security review.

• Panama ports deal: CK Hutchison has taken Panama to arbitration after the Central American country’s top court ruled to kick out the Hong Kong-based conglomerate from ports on its canal.

2. The US has launched an effort to form a trade zone for critical minerals with allies including Japan and the EU. The initiative marks a rare instance of global trade co-operation from the Trump administration, as it works to reduce western reliance on China for a wide range of critical minerals. Here are more details.

• Related: Beijing’s dominance of rare earths has sparked a rush among buyers to source the metals elsewhere, with more than 30 projects set for production this decade.

3. Companies linked to Indonesia’s richest man have announced share buybacks after a market rout triggered by a downgrade warning from index provider MSCI helped wipe out more than a quarter of his net worth. Billionaire Prajogo Pangestu has lost $11.7bn of his wealth since the start of the year amid Indonesia’s worst stock sell-off since the Asian financial crisis of 1998, according to Bloomberg data.

4. Google said it plans to spend at least $55bn more on capital expenditure this year than Wall Street had forecast, as it doubles down on its huge spending on AI. The search giant increased its forecast for capex in 2026 to a range of $175bn to $185bn, far exceeding analysts’ expectations for about $120bn.

• Markets: US tech stocks were hit by a fresh wave of selling yesterday, adding fuel to a sell-off sparked by concerns about the impact of AI on software businesses.

• Anthropic’s new AI tools: The start-up’s advances have rattled markets this week, amid fears of disruption across sectors from publishing and advertising to law.

5. A top Senate Republican has said Fed chair Jay Powell has not “committed a crime”, in a strong rebuke of the Trump administration’s probe into the central bank chief from a senior member of the president’s own party. Read the remarks from Tim Scott, chair of the powerful Senate banking committee.

The Big Read

Sanae Takaichi, the arch-conservative and populist, is on course for a possible landslide in the shortest election campaign in postwar Japanese history. But if the prime minister wins this week’s vote, she will face harsh realities.

We’re also reading . . . 

Chart of the day

When Trump announced a long-awaited US-India trade deal on Monday, the president claimed a commitment by New Delhi to stop buying Russian oil had made the agreement possible. But the reluctance of Indian leaders to confirm such a pledge is fuelling deep scepticism among analysts that any substantial cut is imminent.

Take a break from the news . . . 

Looking for a place to stay in Hong Kong? FT Globetrotter has you covered, from the city’s grandes dames to new design classics.

Atherosclerosis begins early and progresses silently. Patients requiring secondary prevention have already accumulated decades of low-density lipoprotein cholesterol (LDL-C) exposure resulting in some potentially irreversible arterial aging and injury. LDL-C should be conceived of as a marker of cumulative risk rather than a single assessment at a point in time. As Shapiro and Bhatt described, cumulative exposure to LDL-C functions much like pack-years for smoking, predicting not only the likelihood but also the timing and severity of atherosclerotic cardiovascular disease (ASCVD).¹ For true primary prevention of ASCVD, when it comes to LDL-C levels, lower is better for longer.

Decades of genetic, epidemiologic, and clinical evidence summarized in recent meta-analyses and guidelines demonstrate a linear, causal, and cumulative relationship between lifelong elevated LDL-C levels and ASCVD risk.^1,2 Recent data reveal that timing of elevated LDL-C exposure matters as much as the degree of elevation. Domanski et al. demonstrated that both total cumulative LDL-C exposure and the time-weighted mean LDL-C levels were independently predictive of future cardiovascular (CV) events.³ Specifically, exposure prior to 50 years of age may increase risk of CV events more than exposure later in life—a concept consistent with the life-course framework, which emphasizes the ways timing of exposure shapes long-term disease trajectories.⁴ Specifically, lowering LDL-C levels in young adults has a more potent effect in reducing ASCVD incidence than does starting later.

These findings complement recent findings from Wilkins et al. that a single LDL-C or non–high-density lipoprotein cholesterol (HDL-C) measurement obtained between 18 and 30 years of age predicts an individual’s cumulative exposure through 40 years of age with excellent precision.⁵ Participants in the top quartile of early-life non–HDL-C levels >135 mg/dL had a 4.5-fold greater risk of ASCVD after 40 years of age than did those in the lowest quartile. Thus, a single lipid panel in young adulthood can predict decades of risk. For many adults who are open to preventive statin therapy, the questions should be how early and how intensively to start. The 2025 Focused Update of the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidaemias reinforces a proactive approach that calls for consideration of earlier, more aggressive LDL-C lowering in primary prevention rather than waiting for the disease to manifest.²

If cumulative exposure to atherogenic lipoproteins drives ASCVD, it would make sense that earlier LDL-C reduction would yield greater benefit than waiting until moderate atherosclerosis is present. Every 1 mmol/L LDL-C reduction yields approximately 20-25% relative major adverse CV events reduction over 5 years, with absolute risk reduction dependent on baseline risk.² Long-term follow-up of the WOSCOPS (The West of Scotland Coronary Prevention Study) participants demonstrated a persistent legacy benefit of early statin therapy and lower coronary and CV mortality up to 20 years later despite similar LDL-C levels in follow-up.^6,7 A similar legacy effect was observed in the FOURIER-OLE (FOURIER Open-Label Extension) study, an open label extension of the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial. These findings highlight that earlier LDL-C control forestalls atheroma formation and reduce risk of recurrent events, and, thereby, highlight how preventive pharmacotherapy supports healthy vascular aging.

Traditionally, lipid management followed a sequential, stepwise approach. Most patients would start a statin, LDL-C levels would be rechecked months later, and, if targets were unmet despite concomitant efforts at lifestyle improvement, ezetimibe or, more rarely, a proprotein convertase subtilisin/kexin type 9 inhibitor was considered. In contrast, both the 2025 ESC/EAS focused update on dyslipidemia and the 2022 American College of Cardiology (ACC) Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-C Lowering in the Management of ASCVD Risk now recommend consideration of more rapid, intensive lipid-lowering strategies from the start, especially for patients with CV risk–enhancing factors such as elevated lipoprotein(a) levels, elevated high-sensitivity C-reactive protein levels, and health-related social needs.^2,8 Implementation of such guidelines may help overcome the low use of combination lipid-lowering therapy in both Europe and the United States (US).

Under the European model, treatment initiation should be considered when LDL-C levels exceed 100 mg/dL in individuals at moderate risk and 70 mg/dL in those at high risk, with targets of <70 mg/dL for those at moderate risk and <55 mg/dL for those at high risk.² The 2025 ESC/EAS focused update on dyslipidemia elevates bempedoic acid to a class I recommendation on the basis of the CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) trial results and recognizes inclisiran as an alternative.²

Similarly, the 2022 ACC expert consensus decision pathway on LDL-C lowering recommends reassessment within 6 weeks and immediate addition of nonstatin lipid-lowering therapy if LDL-C targets are unmet (<70 mg/dL for individuals at high risk, <55 mg/dL for those at very high risk).⁸ This guidance encourages clinicians to anticipate the need for combination therapy from initiation in patients at high risk.

Beyond clinical benefit, earlier LDL-C lowering is economically optimal. Cost-effectiveness analyses support earlier initiation of lipid-lowering therapy: Statins are cost-effective in adults <40 years of age with LDL-C levels ≥130-160 mg/dL, and starting 10 years earlier likely prevents more events than intensifying therapy later.⁹ In an accompanying editorial, Heidenreich et al. urged the US societies to relax the 40-years-old age threshold and to adopt lifetime risk-guided pharmacologic LDL-C lowering to align with the European prevention principles.¹⁰ Early testing enables earlier treatment rather than delayed reaction. Even modest LDL-C reduction begun early yields exponential economic benefit, which may be thought of as a legacy effect.

Atherogenesis is a cumulative vascular aging process. Every decade of elevated LDL-C levels compounds lifetime risk, whereas each year of earlier LDL-C lowering confers protection. The 2025 ESC/EAS focused update on dyslipidemia emphasizes early prevention by lowering initiation thresholds to 100 mg/dL in groups at moderate risk and to 70 mg/dL those at high risk. By reframing lipid management as lifelong exposure reduction to promote healthy vascular aging rather than reactive correction, clinicians can shift from managing disease to effectively preventing it.

References

1. Shapiro MD, Bhatt DL. “Cholesterol-years” for ASCVD risk prediction and treatment. J Am Coll Cardiol. 2020;76(13):1517-1520. doi:10.1016/j.jacc.2020.08.004
2. Mach F, Koskinas KC, Roeters van Lennep JE, et al. 2025 focused update of the 2019 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2025;46(42):4359-4378. doi:10.1093/eurheartj/ehaf190
3. Domanski MJ, Tian X, Wu CO, et al. Time course of LDL cholesterol exposure and cardiovascular disease event risk. J Am Coll Cardiol. 2020;76(13):1507-1516. doi:10.1016/j.jacc.2020.07.059
4. Zheutlin AR, Handoo F, Luebbe S, et al. Cumulative exposure to atherogenic lipoprotein particles in young adults and subsequent incident atherosclerotic cardiovascular disease. Eur Heart J. 2025;46(41):4302-4312. doi:10.1093/eurheartj/ehaf472
5. Wilkins JT, Ning H, Allen NB, et al. Prediction of cumulative exposure to atherogenic lipids during early adulthood. J Am Coll Cardiol. 2024;84(11):961-973. doi:10.1016/j.jacc.2024.05.070
6. Mhaimeed O, Burney ZA, Schott SL, Kohli P, Marvel FA, Martin SS. The importance of LDL-C lowering in atherosclerotic cardiovascular disease prevention: lower for longer is better. Am J Prev Cardiol. 2024;18:100649. Published 2024 Mar 18. doi:10.1016/j.ajpc.2024.100649
7. Ford I, Murray H, McCowan C, Packard CJ. Long-term safety and efficacy of lowering low-density lipoprotein cholesterol with statin therapy: 20-year follow-up of West of Scotland coronary prevention study. Circulation. 2016;133(11):1073-1080. doi:10.1161/CIRCULATIONAHA.115.019014
8. Writing Committee, Lloyd-Jones DM, Morris PB, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(14):1366-1418. doi:10.1016/j.jacc.2022.07.006
9. Kohli-Lynch CN, Bellows BK, Zhang Y, et al. Cost-effectiveness of lipid-lowering treatments in young adults. J Am Coll Cardiol. 2021;78(20):1954-1964. doi:10.1016/j.jacc.2021.08.065
10. Heidenreich PA, Clarke SL, Maron DJ. Time to relax the 40-year age threshold for pharmacologic cholesterol lowering. J Am Coll Cardiol. 2021;78(20):1965-1967. doi:10.1016/j.jacc.2021.08.072

Opportunities for integrating AI in health care

Establishing relevant frameworks for enabling AI integration

WASHINGTON — The Commodity Futures Trading Commission today announced it has withdrawn the notice of proposed rulemaking titled “Event Contracts” that published June 10, 2024. [See CFTC Press Release No. 8907-24] The CFTC does not intend to issue final rules with respect to the proposal. 

Additionally, Commission staff has withdrawn CFTC Staff Letter 25-36, a Staff Advisory on Certain Contract Markets, issued Sept. 30, 2025 [See CFTC Press Release No. 9137-25].

“Today’s actions reflect the CFTC’s commitment to lawful innovation in our markets,” said CFTC Chairman Michael S. Selig. “The 2024 event contracts proposal reflected the prior administration’s frolic into merit regulation with an outright prohibition on political contracts ahead of the 2024 presidential election. The Commission is withdrawing that proposal and will advance a new rulemaking grounded in a rational and coherent interpretation of the Commodity Exchange Act that promotes responsible innovation in our derivatives markets in line with Congressional intent.”

Chairman Selig also commended the staff’s withdrawal of its 2025 sports event contracts advisory. 

“While intended to highlight litigation considerations, the advisory inadvertently created confusion and uncertainty for our market participants” Chairman Selig said. “I look forward to working with staff on an event contracts rulemaking.”

“Dripping water hollows out stone, not through force but through persistence.” – Ovid

The 2025 American Society of Hematology (ASH) Annual Meeting & Exposition delivered multiple practice-changing datasets surrounding T-cell–redirecting therapies in relapsed or refractory multiple myeloma.

Three abstracts were especially notable: the phase III MajesTEC-3 trial (LBA-6)¹, which paired teclistamab-cqyv with daratumumab and reported striking long-term progression-free and overall survival in relapsed or refractory multiple myeloma treated with one to three prior lines of therapy; the phase II RedirecTT-1 study (Abstract 698)², which tested dual bispecific targeting (GPRC5D and BCMA) in true extramedullary disease; and early results from inMMyCAR (LBA-1)³, which used an intravenously delivered gene therapy (KLN-1010) to generate anti-BCMA chimeric antigen receptor (CAR) T cells in vivo without leukapheresis or lymphodepleting chemotherapy.

For full details of the study abstracts, visit www.hematology.org/meetings/annual-meeting/abstracts.

LBA-6 (MajesTEC-3): Teclistamab Plus Subcutaneous Daratumumab vs Standard Daratumumab Triplets

Background: Daratumumab-based triplets such as daratumumab plus pomalidomide and lenalidomide (DPd) and daratumumab plus bortezomib and lenalidomide (DVd) are commonly used in patients with relapsed or refractory multiple myeloma after one to three prior lines of therapy, but outcomes remain limited, particularly in those previously exposed to proteasome inhibitors and immunomodulatory drugs. Teclistamab, a BCMA × CD3 bispecific antibody, has shown deep and durable responses in later-line disease. In October 2022, teclistamab was granted accelerated approval by the U.S. Food and Drug Administration, based on the results of MajesTEC-1 trial; patients with relapsed or refractory multiple myeloma who received at least three prior lines of therapy and were treated with teclistamab had an overall response rate of 63.0%,^4,5 and 46.1% achieved a complete response or better.⁴ Long-term follow-up from MajesTEC-1 (median follow-up = 30.4 months) showed a median duration of response of 24 months overall, with a 30-month duration of response rate of 60.8% in patients achieving a complete response (median = not reached).⁴ MajesTEC-3 (ClinicalTrials.gov Identifier: NCT05083169) is a phase III trial evaluating teclistamab plus subcutaneous daratumumab earlier in the disease course.^1,6,7

Methods: MajesTEC-3 is an ongoing randomized phase III trial in relapsed or refractory multiple myeloma after one to three prior lines of therapy (including prior lenalidomide and a proteasome inhibitor). Patients with prior BCMA-directed therapy or anti-CD38 antibody refractory disease were excluded. Participants were randomly assigned to receive teclistamab plus subcutaneous daratumumab (n = 291) or investigator’s choice of DPd or DVd (n = 296). Approximately 5% of patients had prior daratumumab exposure, balanced across arms.

After step-up dosing, teclistamab was administered at 1.5 mg/kg weekly in the first and second cycles, then 3 mg/kg every 2 weeks in the third through sixth cycles, and every 4 weeks from the seventh cycle and onward. Subcutaneous daratumumab was given weekly in the first and second cycles, every 14 days in the third through sixth cycles, and every 4 weeks from the seventh cycle and onward. The primary endpoint was progression-free survival by independent review; key secondary endpoints included overall survival, overall response rate, complete response rate, measurable residual disease (MRD) negativity, patient-reported outcomes, and safety.

Efficacy Results: With extended follow-up (median = 34.5 months), teclistamab plus daratumumab produced a marked reduction in the risk of disease progression or death (36-month progression-free survival: 83.4% vs 29.7%; hazard ratio [HR] = 0.17, 95% confidence interval [CI] = 0.12–0.23; P < .0001). Of note, 90% of patients who were progression-free at 6 months remained progression-free at 3 years. Overall survival also favored teclistamab plus daratumumab (36-month: 83.3% vs 65.0%; HR = 0.46, 95% CI = 0.32–0.65; P < .0001). Responses were both more frequent and deeper: the overall response rate was 89.0% vs 75.3% in the control group (odds ratio [OR] = 2.65; P < .0001), and the complete response or better rates were 81.8% vs 32.1% (OR = 9.56, 95% CI = 6.46–14.14; P < .0001). Among evaluable patients, MRD-negative complete response at 10^–5 sensitivity was 57.6% with teclistamab plus daratumumab vs 17.1% with DPd or DVd (OR = 6.78; P < .0001).

Safety Results: Cytokine release syndrome was reported in 60.1% of patients treated with teclistamab plus daratumumab and was predominantly grade 1 (44.2%) or grade 2 (15.9%); no grade 2 cytokine release syndrome occurred after the first cycle, and discontinuations because of cytokine release syndrome were rare. Immune effector cell–associated neurotoxicity syndrome was uncommon (1.1%).

As expected with BCMA-directed T-cell–engaging therapy, infections and hypogammaglobulinemia were common. Any-grade infections were observed in 96.5% of patients treated with teclistamab plus daratumumab vs 84.1% of those who received the control. Thirteen patients (4.6%) treated with teclistamab plus daratumumab died from infection; of these deaths, 12 occurred within 6 months of treatment, including 3 due to COVID-19, and 9 of the 12 had not received immunoglobulin replacement therapy. After a protocol amendment reinforcing immunoglobulin replacement therapy was made, only one infection-related death occurred. Overall, 87.3% of the patients treated with teclistamab plus daratumumab received at least one dose of intravenous immunoglobulin.

Clinical Implications: MajesTEC-3 is the first phase III randomized study to pair a bispecific regimen with concurrent improvements in progression-free survival, overall survival, response depth, and MRD negativity in relapsed or refractory multiple myeloma treated with one to three prior lines of therapy. The unprecedented efficacy results support teclistamab plus daratumumab as a potential new standard of care for appropriately selected patients with one to three prior lines of therapy who are not refractory to anti-CD38 monoclonal antibodies. Broad adoption will hinge on standardized infection prevention pathways (eg, early intravenous immunoglobulin/immunoglobulin replacement therapy, vaccination strategy, and antimicrobial prophylaxis) and on defining sequencing vs BCMA-directed CAR T-cell therapy.

698 (RedirecTT-1): Talquetamab-tgvs Plus Teclistamab in Relapsed or Refractory Multiple Myeloma With Centrally Confirmed True Extramedullary Disease

Background: True extramedullary disease—defined as bone-independent soft-tissue or organ plasmacytomas—remains among the highest-risk manifestations of myeloma and is associated with heterogeneous antigen expression and immune microenvironment features, as well as inferior response rates and survival compared with patients without true extramedullary disease.^8,9 Extramedullary disease lesions can be biologically heterogeneous, including variable expression of BCMA and GPRC5D, raising the possibility that dual antigen targeting could mitigate antigen escape.^10,11 RedirecTT-1 (ClinicalTrials.gov Identifier: NCT04586426) tested dual antigen targeting with talquetamab (GPRC5D × CD3) plus teclistamab in this high-risk population.^2,12,13

Methods: Eligible patients had triple-class–exposed relapsed or refractory multiple myeloma with centrally confirmed true extramedullary disease (n = 90)—defined as at least one nonirradiated, bone-independent soft-tissue plasmacytoma measuring at least 2 cm in greatest dimension, confirmed by central PET/CT review. Nonsecretory and oligosecretory myeloma were allowed. Prior anti-BCMA CAR T-cell therapy and non-BCMA/non-GPRC5D bispecific therapy were permitted; the median time from CAR T-cell therapy to study treatment was 295 days (range: 98–1,030 days).

Talquetamab and teclistamab were administered subcutaneously on the same day (30 ± 10 minutes apart) with three step-up doses given 2 to 4 days apart, followed by full doses of 0.8 mg/kg of talquetamab every 2 weeks and 3.0 mg/kg of teclistamab every 2 weeks. Patients were permitted to transition to monthly dosing after four cycles if they achieved a very good partial response or better, or after six cycles irrespective of response.

The primary endpoint was overall response rate by an independent review committee per International Myeloma Working Group (IMWG) criteria; extramedullary disease response incorporated centralized PET/CT assessment using the Deauville 5-point scale and IMPeTUs criteria.^14,15

Efficacy Results: At a median follow-up of 16.8 months, the overall response rate was 79% (95% CI = 69%–87%), including complete responses or better in 54% of patients. The median time to first response was 2.6 months (range: 1.0–5.8 months), and the median time to best response was 5.1 months (range: 1.0–16.6 months). Responses appeared durable: 62% of patients had an ongoing response at 12 months, and the median duration of response was not reached (95% CI = 11.5 months–not estimable). With extended follow-up, the report cited a median progression-free survival of 15 months; 91% of patients maintained or deepened response in the 6 months following protocol-defined de-escalation to monthly dosing.

Safety Results: Safety was generally consistent with the known profiles of each bispecific. Any-grade and grade 3 or 4 infections occurred in 80% and 33% of the population, respectively; pneumonia and COVID-19 were among the most frequent serious infections. Opportunistic infections were reported in 6.7% (grade 3/4: 3.3%) of patients. Hypogammaglobulinemia was frequent after treatment (71%), and 86% of patients received at least one dose of immunoglobulin replacement therapy. Cytokine release syndrome was observed in 77.8% of patients and was largely low grade. After switching from every-2-week to monthly dosing, new-onset key toxicities were less frequent. Adverse events resulted in death in 10 patients, including 5 infection-related deaths.

Clinical Implications: Dual bispecific targeting of GPRC5D and BCMA produced unusually deep and durable responses in centrally confirmed true extramedullary disease—an outcome that could materially change expectations for this subgroup if replicated. The data also underscore that dose/interval de-escalation is not merely a convenience strategy but may be a critical safety lever to reduce cumulative toxicity while preserving response. In summary, this off-the-shelf bispecific antibody combination regimen offers clinically meaningful efficacy for one of the most challenging-to-treat subgroups of patients with multiple myeloma.

LBA-1 (inMMyCAR): In Vivo Gene Therapy to Generate Anti-BCMA CAR T Cells Without Lymphodepletion

Background: Despite major advances with ex vivo–manufactured BCMA-directed CAR T-cell therapies, delivery remains constrained by leukapheresis, centralized manufacturing, time to infusion, and the need for lymphodepleting chemotherapy—factors that can limit access, increase cost, and add toxicity. The inMMyCAR trial (ClinicalTrials.gov Identifier: NCT07075185) explores an investigational approach to overcome the access and logistical constraints of ex vivo CAR T-cell therapy.^3,16 KLN-1010 is an intravenously administered, replication-incompetent lentiviral vector designed to transduce circulating T cells in vivo, generating a fully human anti-BCMA CAR T-cell population without leukapheresis, centralized manufacturing, or lymphodepleting chemotherapy.

Methods: This first-in-human multicenter phase I study uses a 3 + 3 dose-escalation design with primary objectives of safety/tolerability and selection of a recommended phase II dose. Eligibility includes relapsed or refractory multiple myeloma with measurable disease after at least three prior lines of therapy, including prior exposure to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, with an Eastern Cooperative Oncology Group performance status of 0 to 1 and adequate organ function. The ASH presentation summarized the outcomes of the first four treated patients (three treated at dose level 1 and one treated at dose level −1), with follow-up through at least month 3 in those with the longest observation.

Efficacy Results: KLN-1010 generated measurable CAR T cells in vivo, with peak expansion around day +15. CAR-positive cells comprised a substantial fraction of circulating CD3-positive T cells (at day +15: 22%–72% in dose level 1; 85% in dose level −1). No adverse clinical sequelae were attributed to lymphocytosis during expansion, and dexamethasone promptly resolved lymphocytosis in the patient with the highest level. Circulating CAR T cells were detectable in peripheral blood and bone marrow through month 3 and were predominantly memory phenotype, a feature historically associated with durable remissions after ex vivo CAR T-cell therapy.

All treated patients (n = 4; 100%) achieved early MRD negativity at month 1 by next-generation flow cytometry or next-generation sequencing (10^–5–10^–6 sensitivity), with sustained MRD negativity through month 2 in the two patients with the longest follow-up.

SafetyResults: Treatment-emergent adverse events clustered around infusion and the period of CAR T-cell expansion. Infusion-related reactions were early and generally self-limited; after an initial reaction, prophylactic tocilizumab was incorporated. Cytokine release syndrome occurred with a median onset of 10 days (range: 10–12 days) and was limited to grade 1 to 2, with no grade 3 or higher events reported. Management included supportive care with tocilizumab and/or dexamethasone when indicated. No immune effector cell–associated neurotoxicity syndrome or delayed neurotoxicity (eg, parkinsonism or cranial nerve palsies) was reported in this early cohort, and cytopenias appeared limited compared with typical ex vivo CAR T-cell experiences.

Clinical Implications: These preliminary first-in-human observations provide proof of concept for an off-the-shelf in vivo CAR T-cell platform, with the potential to shorten time to treatment and reduce the intensity of supportive care required for lymphodepletion-related cytopenias. If durability and safety are confirmed with longer follow-up and across dose levels, in vivo CAR T-cell platforms such as KLN-1010 could significantly advance the field of CAR T-cell therapy. By simplifying logistics, shortening time to treatment, and potentially enabling outpatient delivery, in vivo CAR T-cell products may meaningfully expand access to cellular therapy for appropriate patients with relapsed or refractory multiple myeloma. The study remains ongoing. ν

DISCLOSURE: Dr. Abutalib reported a relationship with AstraZeneca. Dr. Pianko has received research funding and/or consulting fees from AbbVie, AstraZeneca, Bristol Myers Squibb/Celgene, Janssen, Karyopharm, Kite/Gilead, GlaxoSmithKline, Oncopeptides, Pfizer, Regeneron, and Sanofi.

REFERENCES

1. Mateos M-V, Bahlis N, Perrot A, et al: Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib in patients with relapsed refractory multiple myeloma: Results of majestec-3. 2025 ASH Annual Meeting & Exposition. Abstract LBA-6. Presented December 8, 2025.

2. Usmani S, Kumar S, Mateos MM, et al: Efficacy and safety of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: Updated phase 2 results from the redirectt-1 study with extended follow-up. 2025 ASH Annual Meeting & Exposition. Abstract 698. Presented December 2025.

3. Harrison S, Ho PJ, Lim S-L, et al: Minimal residual disease-negative outcomes following a novel, in vivo gene therapy generating anti–B-cell maturation antigen chimeric antigen receptor-T cells in patients with relapsed and refractory multiple myeloma: Preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010. 2025 ASH Annual Meeting & Exposition. Abstract LBA-1. Presented December 2025.

4. Garfall AL, Nooka AK, van de Donk NWCJ, et al: Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol 42:7540, 2024.

5. Moreau P, Garfall AL, van de Donk NWCJ, et al: Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med 387:495-505, 2022.

6. Mateos M-V, Bahlis N, Perrot A, et al: Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib in patients with relapsed refractory multiple myeloma: Results of majestec-3. Blood 146:LBA-6, 2025.

7. Costa LJ, Bahlis NJ, Perrot A, et al: Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. December 9, 2025 (early release online).

8. Bladé J, Beksac M, Caers J, et al: Extramedullary disease in multiple myeloma: A systematic literature review. Blood Cancer J 12:45, 2022.

9. Rosiñol L, Beksac M, Zamagni E, et al: Expert review on soft-tissue plasmacytomas in multiple myeloma: Definition, disease assessment and treatment considerations. Br J Haematol 194:496-507, 2021.

10. John M, Helal M, Duell J, et al: Spatial transcriptomics reveals profound subclonal heterogeneity and T-cell dysfunction in extramedullary myeloma. Blood 144:2121-2135, 2024.

11. Zanwar S, Novak J, Gonsalves W, et al: Extramedullary myeloma is genomically complex and characterized by near-universal MAPK pathway alterations. Blood Adv 9:3979-3987, 2025.

12. Kumar S, Mateos M-V, Ye JC, et al: Dual targeting of extramedullary myeloma with talquetamab and teclistamab. N Engl J Med 394:51-61, 2026.

13. Usmani S, Kumar S, Mateos M-V, et al: Efficacy and safety of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: Updated phase 2 results from the redirectt-1 study with extended follow-up. Blood 146:698, 2025.

14. Nanni C, Zamagni E, Versari A, et al: Image interpretation criteria for FDG PET/CT in multiple myeloma: A new proposal from an Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET USe). Eur J Nucl Med Mol Imaging 43:414-421, 2016.

15. Zamagni E, Nanni C, Dozza L, et al: Standardization of 18F-FDG–PET/CT according to Deauville criteria for metabolic complete response definition in newly diagnosed multiple myeloma. J Clin Oncol 39:116-125, 2021.

16. Harrison S, Ho PJ, Lim S-L, et al: Minimal residual disease-negative outcomes following a novel, in vivo gene therapy generating anti–B-cell maturation antigen chimeric antigen receptor-T cells in patients with relapsed and refractory multiple myeloma: Preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010. Blood 146:LBA-1, 2025.

Dr. Abutalib is Director of the Malignant Hematology and Transplantation & Cellular Therapy Programs at the Advocate/Aurora St. Luke’s Medical Center, Milwaukee, and Associate Professor at Rosalind Franklin University of Medicine and Science, Chicago. Dr. Pianko is Clinical Associate Professor of Internal Medicine at the University of Michigan, Ann Arbor, and a member of the Multiple Myeloma & Amyloidosis Program at the Rogel Cancer Center of the University of Michigan.