Courtney Flaherty 

KLN-1010 was associated with deep, ongoing minimal residual disease (MRD)–negative responses in multiple myeloma.

In four patients with relapsed/refractory multiple myeloma, the investigational, 

 BCMA-directed CAR-T therapy–generating agent KLN-1010 was associated with deep, ongoing minimal residual disease (MRD)–negative responses, and the treatment had a favorable safety profile as an off-the-shelf product, clinical trial data have shown.

First-in-human results from the phase 1 inMMyCAR trial were presented during the 2025 ASH Annual Meeting.

Responses deepened over time, with patient 1 achieving a complete response at a MRD sensitivity level of 10

 after month 5; patient 2 achieving a partial response (PR) at a MRD sensitivity level of 10

during month 4; patient 3 achieving a PR at a MRD sensitivity level of 10

during month 3; and patient 4 achieving a PR at a MRD sensitivity level of 10

at the beginning of month 2. Of note, in the first two patients with the longest follow-up, MRD-negative bone marrow responses were sustained through three months.

Minimal residual disease (MRD): A very small number of cancer cells that remain in the body after treatment. These cells are too few to cause symptoms but can be detected with sensitive tests.

Complete response: All signs of cancer disappear after treatment. This does not always mean the cancer is cured, but no cancer can be found on tests.

Partial response: The cancer shrinks but does not go away completely.

Immune effector cell–associated neurotoxicity syndrome (ICANS): A temporary side effect that can occur after immune-based therapies (like CAR-T cells). It can cause confusion, trouble speaking, headaches or drowsiness.

Cytokine release syndrome (CRS): A reaction that happens when the immune system becomes very active during certain cancer treatments. It may cause fever, low blood pressure, or trouble breathing.

Infusion-related reaction (IRR): Symptoms such as fever, chills, rash or low blood pressure that can occur during or shortly after a medicine is given by infusion.

Lymphocytosis: A higher-than-normal number of lymphocytes (a type of white blood cell). Sometimes this happens as part of the body’s response to treatment.

Lymphopenia: A lower-than-normal number of lymphocytes, which may increase the risk of infection.

Neutropenia: A low level of neutrophils (another type of white blood cell), which increases infection risk.

Febrile neutropenia: A fever that occurs when neutrophil levels are very low. This is considered an emergency because it can signal a serious infection.

Anemia: A low red blood cell count. This can cause tiredness, shortness of breath, or dizziness.

Thrombocytopenia: A low platelet count. Platelets are needed for blood clotting, so low levels may lead to easy bruising or bleeding.

Hypomagnesemia: Low magnesium levels in the blood. This may cause muscle cramps, weakness, or abnormal heart rhythms.

Hypokalemia: Low potassium levels in the blood. Symptoms may include fatigue, muscle weakness, or irregular heartbeat.

Vasovagal syncope: A brief fainting episode caused by a sudden drop in heart rate and blood pressure, often triggered by pain, stress, or medical procedures.

CAR-T cell expansion occurred despite the absence of lymphodepleting chemotherapy. All patients experienced a rise in lymphocyte count. Dexamethasone was administered to patients 3 and 4 with prompt resolution and no clinical sequelae. Additionally, CAR-positive T cells were detected in the blood at day 15 at rates of 35%, 22%, 72% and 85%, and comprised a mixture of CD4 and CD8 CAR T-cells. Of note, the highest level of CAR-positive cells was achieved at dose level –1.

“These initial MRD-negative responses and persistent CAR-T cell [expansion may be] prognostic of ongoing clinical responses,” presenting author Phoebe Joy Ho, a professor at the University of Sydney, shared. “Establishing durability of response [DOR] remains a priority in continued follow-up, and updated results will be presented at future meetings.”

Ho is also a senior staff specialist in hematology, the director of research, and head of the Multiple Myeloma Research Unit and Thalassemia/Haemoglobinopathy Unit at the Institute of Haematology, Royal Prince Alfred Hospital in Sydney, Australia.

Why was KLN-1010 chosen for investigation in this patient population, and what makes its mechanism of action unique?

KLN‑1010 is an envelope-modified, replication-incompetent, self-inactivating modified lentiviral vector gene therapy administered intravenously to generate novel, fully-human anti-BCMA CAR-T cells in vivo. Designed as an off-the-shelf therapy, KLN-1010 eliminates the need for preconditioning lymphodepleting chemotherapy, simplifies the logistics of CAR-T cell administration, and may increase T-cell fitness through the absence of ex vivo culture, all of which could improve access to CAR-T cell therapies, Ho explained.

inMMyCAR is a first-in-human, dose-escalation/-expansion study conducted at three different sites in Australia: Peter MacCallum Cancer Center, The Alfred Hospital and Royal Prince Alfred Hospital. The study plans to enroll approximately 20 patients with relapsed/refractory multiple myeloma who received three or more lines of prior therapy, including a proteasome inhibitor (PI), immunomodulatory drug (IMiD) or anti-CD38 antibodies. Other eligibility criteria include an ECOG performance status of 0 or 1 and adequate bone marrow or organ function.

The ages of patients 1, 2, 3 and 4 were 72 years, 62 years, 61 years and 70 years, respectively. Patients 1 and 4 were male; patients 2 and 3 were female. These patients received 4, 3, 3 and 5 prior lines of therapy, respectively. Patients 1, 3, and 4 were all refractory to PIs, IMiDs, and anti-CD38 antibodies; patient 2 was only refractory to IMiDs and anti-CD38 antibodies. No patients had extramedullary disease and all patients had previously undergone autologous stem cell transplant.

What should be known about the agent’s safety profile?

Investigators did not observe any instances of immune effector cell–associated neurotoxicity syndrome or delayed neurotoxicity. Moreover, all cases of cytokine release syndrome (CRS) were low-grade, and CRS events were consistent with those seen with 

CAR-T cell therapies. The median onset of CRS was 10 days, and the median duration was 5.5 days. Two Grade 1 (mild)/2 (moderate) CRS events occurred at dose level 1, and 1 grade 1/2 CRS event occurred at dose level –1. Dexamethasone and Actemra (tocilizumab) were administered as supportive care measures (three patients each).

Treatment-emergent side effects that occurred in more than one patient included Infusion-related reactions (IRR; grade 1/2, two patients; grade 3 (severe) or higher, one patient [dose-limiting toxicity]), lymphocytosis (one patient each), hypomagnesemia (two and zero patients), and hypokalemia (two and zero patients). Grade 3 or higher treatment-emergent side effects included febrile neutropenia, IRR, lymphopenia, lymphocytosis, anemia, vasovagal syncope and pneumonia (one patient each).

Cytopenias were also minimal, with only one case of grade 4 (life-threatening) transient neutropenia reported. Grade 3 or higher anemia and thrombocytopenia occurred in one patient each on study days 15 and 16, respectively, and lasted for two days. Two patients experienced grade 3 or higher neutropenia. One grade 1/2 and one grade 3 or higher IRR occurred at dose level 1; tocilizumab and steroids were administered as supportive care. One grade 1/2 IRR occurred at dose level –1, and paracetamol was administered as supportive care.

This favorable safety and tolerability profile, which was achieved with an off-the-shelf product, suggests that outpatient administration of KLN-1010 may be feasible, Ho concluded.

“Minimal residual disease (MRD)-negative outcomes following a novel, in vivo gene therapy generating anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells in patients with relapsed and refractory multiple myeloma (RRMM): preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010: results of a phase 2 trial” by Phoebe Joy Ho et al., 

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Articles

KLN-1010, an investigational BCMA-directed CAR-T therapy, demonstrated promising MRD-negative responses in patients with relapsed/refractory multiple myeloma, with a favorable safety profile. The phase 1 inMMyCAR trial showed deepening responses over time, with sustained MRD-negative bone marrow responses in patients with longer follow-up. The therapy, administered without lymphodepleting chemotherapy, resulted in CAR-T cell expansion and manageable side effects. KLN-1010's unique mechanism simplifies CAR-T administration and may enhance T-cell fitness, potentially improving access to CAR-T therapies for multiple myeloma patients.

Off-The-Shelf CAR-T KLN-1010 Associated With Deep Responses in R/R Myeloma

Lutathera demonstrated antitumor activity in metastatic bronchopulmonary neuroendocrine tumors: © stock.adobe.com.

Lutathera showed antitumor activity in patients with metastatic bronchopulmonary neuroendocrine tumors, based on real-world data presented at the IASLC 2025 World Conference on Lung Cancer.

Among patients treated with Lutathera (23 patients), partial responses, stable disease and progressive disease occurred in 17%, 30% and 23% of patients, respectively.

“In clinical practice, the decision of when to utilize peptide receptor radionuclide therapy varies widely, found here most commonly as a third-line systemic agent,” Dr. Giuseppe Maiocco, a resident in the Division of Internal Medicine at the Mayo Clinic and coauthors wrote in a poster presentation.

What Are the Background and Design of this Real-World Study?

Lutathera is a peptide receptor radionuclide therapy and has emerged as a promising treatment in neuroendocrine tumors with selective targeting of somatostatin receptor–expressing cells.

In April 2024, the FDA approved Lutathera for the treatment of patients 12 years of age or older with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. This regulatory decision represented the first FDA approval of a radioactive drug or radiopharmaceutical for this patient population.

Of note, BP-NETs comprise approximately 20% to 30% of neuroendocrine tumors and the management of metastatic BP-NETs requires substantial tailoring. Accordingly, the objective of this real-world study was to evaluate the real-world use of Lutathera in patients with BP-NETs.

In the retrospective analysis, patients with metastatic BP-NETs were treated with peptide receptor radionuclide therapy at Mayo Clinic sites in Arizona, Florida and Minnesota between 2014 and 2025. Notably, tumor grade was defined by Ki-67 score and histology was defined per World Health Organization 2017 criteria.

Primary outcomes included response rates, progression-free survival and overall survival. Response rates were assessed by 3-month post-treatment interval restaging imaging and clinician document assessment. Progression-free survival was defined as therapy initiation to any disease progression, last follow-up or death; overall survival was defined as therapy initiation to last follow-up or death.

What Were the Baseline Patient Characteristics?

In the patient population, the median age was 66 years, 39% were female and 48% had a history of tobacco use. Metastatic sites included liver (78%), bone (61%), pancreas (9%) and contralateral lung (4%). Additionally, patients had grade 1 (26%), grade 2 (39%) or grade 3 (26%) disease per World Health Organization 2017 criteria. Carcinoid histology was either typical (43%) and atypical (57%). Furthermore, the majority of patients were nonfunctional (70%), had a Krenning scale score of 4 (57%) and an ECOG performance status of 0 (57%). The median number of therapy treatments was 4. Regarding treatment history, more than half of patients received 2 systemic treatments before therapy (52%). Preceding treatments included somatostatin analog (100%), chemotherapy (65%) with 43% of patients treated with single-line chemotherapy, Afinitor (43%) and a tyrosine kinase inhibitor (9%). Notably, 43% of patients did not receive systemic treatments following therapy.

What Other Efficacy and Safety Data Were Reported?

In all patients, the median progression-free survival was 10.8 months. Moreover, in patients with typical and atypical carcinoid histology, the median progression-free survival was 11.1 months and 8.4 months. Those with a Krenning score of 4 and a Krenning score of 3 or less had a median progression-free survival of 14.7 months and 7.3 months.

The median overall survival in all patients was 35.6 months. Patients with typical and atypical carcinoid histologies had a median overall survival of 35.5 months and 19.8 months. Patients with a Krenning score of 4 or a Krenning score of 3 or less had a median overall survival of 24.4 months and 16.5 months.

Regarding side effects, the most common treatment-related side effects included fatigue (35%), nausea (26%), abdominal pain (22%) and decreased appetite (13%).

“Lutathera was well tolerated, with no grade 3 or higher side effects,” Maiocco and coauthors concluded in the poster presentation.

Maiocco G, Hazim A, Halfdanarson T, et al. Real-world outcomes of patients with bronchopulmonary neuroendocrine tumors treated with Lutetium Lu-177 dotatate. Presented at: International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract P3.13.32.

FDA approves lutetium Lu 177 dotatate for pediatric patients 12 years or older with GEP-NETS. FDA. April 23, 2024. Accessed September 9, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-dotatate-pediatric-patients-12-years-and-older-gep-nets

Lutathera, a peptide receptor radionuclide therapy, demonstrated antitumor activity in patients with metastatic bronchopulmonary neuroendocrine tumors (BP-NETs) in a real-world study. The study, conducted at Mayo Clinic sites, assessed response rates, progression-free survival, and overall survival among patients treated with Lutathera. Results showed a median progression-free survival of 10.8 months and a median overall survival of 35.6 months. The treatment was well-tolerated, with common side effects including fatigue, nausea, and abdominal pain, and no grade 3 or higher side effects were reported.

Lutathera demonstrated antitumor activity in patients with metastatic bronchopulmonary neuroendocrine tumors.

Real-World Study Finds Benefit of Lutathera in Patients With Lung NETs 

Nubeqa plus hormone therapy improved progression-free survival and delayed PSA progression in metastatic prostate cancer with manageable side effects.

While the addition of Nubeqa (darolutamide) to androgen deprivation therapy proved clinically beneficial among patients with metastatic hormone-sensitive prostate cancer, the nurse’s role in educating patients on its effect and its safety is key, according to Brenda Martone, registered nurse and advanced practice provider.

At the 50th Annual Oncology Nursing Society Congress, safety and efficacy data from the phase 3 ARANOTE study were shared with oncology nurses so that they can better educate, and counsel patients being treated with this approach. The data, which were shared in a poster and previously presented, underscored that the Nubeqa combination (446 patients) resulted in a 46% reduction in the risk of radiological progression or death versus placebo and androgen deprivation therapy (223 patients). The median radiological progression-free survival in these respective arms was not reached versus 25 months, respectively. The 24-month radiological progression-free survival rate was 70.3% with Nubeqa versus 52.1% without it.

A positive trend in overall survival was also observed, with Nubeqa plus androgen deprivation therapy leading to a 19% reduction in the risk of death versus androgen deprivation therapy alone. Moreover, the Nubeqa combination led to a 60% reduction in risk of progression to metastatic castration-resistant prostate cancer; the median time to metastatic castration-resistant prostate cancer in these respective arms was not reached and 13.8 months.

A higher proportion of patients in the Nubeqa arm achieved undetectable prostate-specific antigen, defined as less than 0.2 nanograms per milliliter, versus those in the placebo arm, at 62.6% and 18.5%, respectively. The addition of Nubeqa to androgen deprivation therapy also delayed time to prostate-specific antigen progression, leading to a 69% reduction in the risk of prostate-specific antigen progression. The median time to prostate-specific antigen progression in the Nubeqa arm was not reached versus 16.8 months in the placebo arm.

Lastly, Nubeqa demonstrated clear benefits over placebo in terms of time to pain progression, an important patient-relevant end point. The median time to pain progression was not reached with Nubeqa versus 29.9 months without, translating to a 28% reduction in the risk of pain progression.

“When discussing treatment options with patients, it is important to consider efficacy, safety, and the impact of treatment on patients’ quality of life, and nurses play an important role in providing education to help patients manage disease symptoms and treatment side effects,” Martone, of Northwestern University, Feinberg School of Medicine in Chicago, and colleagues wrote in a poster of the data. “Together with the positive results of the phase 3 ARASENS study, the findings from ARANOTE provide the option to select treatment in metastatic hormone-sensitive prostate cancer with and without Taxotere to meet patients’ individual needs and preferences.”

The incidence of side effects was reported to be low and comparable between the treatment arms. Any side effects were experienced by 91% of those in the Nubeqa arm versus 90% of those in the placebo arm; grade 3 (severe) or 4 (life-threatening) side effects were experienced by 30.8% and 30.3% of patients, respectively. Moreover, serious side effects were reported in 23.6% of those who received Nubeqa plus androgen deprivation therapy versus 23.5% of those who only received androgen deprivation therapy.

Notably, a smaller proportion of patients in the Nubeqa arm experienced side effects that led to treatment discontinuation versus those in the placebo arm, at 6.1% versus 9%, respectively. Authors underscored that this is a “measure of drug tolerability.”

Moreover, the incidence of side effects linked with androgen receptor inhibitor therapy was low in both arms. Side effects included hypertension (Nubeqa, 9.4%; placebo, 9.5%), vasodilation or flushing (9.2%; 7.2%), diabetes or hyperglycemia (9%; 9.5%), cardiac arrhythmias (8.8%; 6.8%), fatigue (5.6%; 8.1%), rash (4.3%; 3.6%), bone fracture (4%; 2.3%), coronary artery disorders (3.6%; 1.4%), mental impairment (1.6%; 0.5%), falls (1.3%; 0.9%) and heart failure (0.9%; 0.9%).

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Nubeqa (darolutamide) combined with androgen deprivation therapy significantly benefits patients with metastatic hormone-sensitive prostate cancer, reducing risks of radiological progression, death, and progression to metastatic castration-resistant prostate cancer. The ARANOTE study highlighted a 46% reduction in radiological progression risk and a 19% reduction in death risk. Nurses play a crucial role in patient education regarding treatment efficacy, safety, and quality of life. Side effects were comparable between treatment arms, with a lower discontinuation rate in the Nubeqa group, indicating good drug tolerability.

Nubeqa plus hormone therapy improved outcomes in metastatic prostate cancer, reducing disease progression and showing a favorable safety profile.

Nubeqa Combo Improves Outcomes in Metastatic Prostate Cancer

Early and late responders with ESCC experienced comparable OS benefits with Tevimbra plus chemo.

Patients with locally advanced, unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who responded to first-line Tevimbra (tislelizumab) plus chemotherapy showed improved overall survival (OS) with deeper responses and a longer time to maximum response, according to data from the phase 3 RATIONALE-306 study presented at the 

2025 ASCO Gastrointestinal Cancers Symposium.

As of November 24, 2023, 68.3% (207 patients) of patients in the intention-to-treat population who received Tevimbra plus chemotherapy achieved a response, with a median time to response of 6.1 weeks. Most responses (64.7%) were achieved within eight weeks of treatment; 22.2% of responses were achieved after eight weeks, up to and including 14 weeks; and 13% of responses were achieved after 14 weeks.

Overall survival: the time from diagnosis or treatment initiation when a patient with cancer is still alive.

Time to maximum response: time it takes for a patient’s tumor to reach the greatest degree of shrinkage or response to treatment.

Intention-to-treat population: a group of patients who were randomly assigned to receive a particular treatment, whether or not they actually received that treatment or adhered to it.

Depth of response rate: how much a tumor shrinks in response to therapy.

ECOG performance status of 0 or 1: a tool used by clinicians to assess a patient’s overall health and ability to perform daily activities. A status of 0 indicates that a patient is fully active and has no restrictions. With a status of 1, a patient is restricted in strenuous physical activity but is able to carry out light housework or sedentary activities.

Overall response rate: the percentage of patients whose cancer shrinks or disappears entirely after treatment.

PD-L1 tumor area positivity score of 10% or greater: at least 10% of the tumor area of covered by PD-L1-positive cells, which are proteins found on some cancer cells that helps cancer cells evade the immune system.

For patients in these three time-to-response groups, the median OS was 21.8 months, 23.1 months and 29 months, respectively. The median OS after first response in these respective groups were 21.3 months, 21.3 months and 23.2 months.

“In the [Tevimbra] plus chemotherapy arm, 64.7% of responders achieved a response within eight weeks, while still 35.2% of responders achieved response at later assessments,” lead study author Dr. Yi Li, of Fifth Medical Center, Chinese PLA General Hospital in Beijing, China, and colleagues wrote in a poster presentation of the data. “[However,] the [OS] benefits were comparable between early responders and late responders.”

The depth of response rate among responders to Tevimbra plus chemotherapy was 62.1%. Over half (50.2%) of responders achieved a depth of response above 50% up to and including 80%; a depth of response above 30% up to and including 50% was observed in 29.8% of responders; and a depth of response greater than 80% up to and including 100% was observed in 20% of responders. Among these three depth-of-response groups, the median OS was 23.7 months, 16.1 months and 34.5 months, respectively.

Among responders, the median time to maximum response was 19 weeks. Maximum response was achieved within 14 weeks, after 14 weeks up to and including 28 weeks, and after 28 weeks in 32.7%, 34.6% and 32.7% of responders, respectively. The median OS for patients in these respective time to maximum response categories was 14.3 months, 17.4 months and 39.9 months. The median OS after maximum response was 12.6 months, 14.3 months and 24.8 months, respectively.

RATIONALE-306 was a trial that enrolled patients at least 18 years of age with unresectable locally advanced or metastatic ESCC, no prior systemic treatment for advanced disease, an ECOG performance status of 0 or 1, and measurable or evaluable disease. Upon enrollment, patients were randomly assigned to receive Tevimbra or placebo intravenously once every three weeks alongside chemotherapy. Treatment continued until disease progression or unacceptable toxicity.

The study’s primary end point was OS in the intention-to-treat patient population. Key secondary end points included progression-free survival, overall response rate, duration of response, OS in patients with a PD-L1 tumor area positivity score of 10% or greater, and safety. Notably, tumor response was assessed every six weeks for the first 48 weeks and every nine weeks thereafter.

Disclosures: Dr Li has no relationships to disclose.

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Response characteristics of tislelizumab (TIS) plus chemotherapy (chemo) in first-line (1L) treatment of locally advanced or metastatic esophageal squamous cell carcinoma (ESCC): a post hoc analysis of RATIONALE-306. Dr Yi Li, et al. 

Patients with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma (ESCC) showed improved overall survival (OS) when treated with Tevimbra (tislelizumab) plus chemotherapy, as per the phase 3 RATIONALE-306 study. The study revealed that 68.3% of patients achieved a response, with a median time to response of 6.1 weeks. The depth of response and time to maximum response were significant factors influencing OS. The trial's primary endpoint was OS, with secondary endpoints including progression-free survival and overall response rate.

Early and late responders with esophageal squamous cell carcinoma experienced comparable OS benefits with Tevimbra plus chemo in the RATIONALE-306 trial.

Courtney Flaherty

Off-The-Shelf CAR-T KLN-1010 Associated With Deep Responses in R/R Myeloma

Real-World Study Finds Benefit of Lutathera in Patients With Lung NETs

Nubeqa Combo Improves Outcomes in Metastatic Prostate Cancer

Tevimbra Plus Chemotherapy May Improve Survival in First-Line ESCC

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