SAN DIEGO — Patients with mantle cell lymphoma (MCL) and undetectable minimal residual disease (uMRD) after induction therapy did not live longer if they underwent hematopoietic cell transplantation (HCT), a randomized trial showed.
After a median follow-up of 2.7 years, patients treated with rituximab (Rituxan) and transplantation had a 3-year overall survival (OS) of 82.1% versus 82.7% among patients who received only rituximab. Progression-free survival (PFS) at 3 years also did not differ significantly between the two groups. Separate analyses of all patients and only those treated according to protocol yielded similar results.
A separate analysis of patients with detectable MRD status after induction suggested that those who converted to uMRD after transplantation did live longer, reported Timothy Fenske, MD, of the Medical College of Wisconsin in Milwaukee, at the American Society of Hematology (ASH) annual meeting.
“In the era of highly effective induction and maintenance regimens for mantle cell lymphoma, patients with undetectable MRD … did not benefit from consolidation autologous transplantation,” Fenske said during a press briefing. “The patients who remain MRD positive after induction may benefit from [autologous] transplant. In particular, the patients who converted to undetectable MRD post-transplant appear to have improved survival and progression-free survival. I would emphasize that longer follow-up will be important to confirm that these findings hold up.”
Following the presentation, Fenske said no consensus existed about the value of stem cell transplant in the setting of uMRD when the trial started. However, younger, fit patients with MCL would often undergo stem cell transplant. Use of MRD to inform treatment decisions also was not standard practice.
“I think [the study] could be practice changing, because if there is a small subset that may still benefit from transplant that we can identify with MRD testing, I think it may be important to identify those patients,” he said. “At the same time, we can spare the majority, because among the patients we tested for MRD, over 70% were MRD negative. If we can safely spare those patients from the potential toxicities of transplant, I think that’s a big step forward.”
“Historically, I think it’s somewhere in the range of 1-2% of patients who die from complications of transplant, and other patients will experience toxicities and effects on their quality of life. For some of our patients going through that, I think that alone will be a big step forward.”
Press briefing moderator Mikkael Sekeres, MD, of the Sylvester Comprehensive Cancer Center and University of Miami in Florida, asked Fenske whether MRD testing should be standard of care for determining transplant eligibility.
“Second, if [patients are] MRD negative in your practice, will you now eliminate the transplant decision as an option?” asked Sekeres.
Said Fenske, “Based on our data and also based on the recently published TRIANGLE study in Europe, we have two studies that suggest that we can safely omit the stem cell transplant in the majority of patients. I do think that identifying the MRD-positive patients is important, since it does appear that those patients may still benefit from transplant. In my practice, I would do this testing so that we can differentiate these two populations.”
Patients with MCL in first remission often undergo transplantation, a strategy based on nonrandomized phase II studies and one randomized trial. The issue has become controversial with the emergence of more effective therapies for MCL, said Fenske. Two years ago at ASH, a report from the TRIANGLE study group showed that HCT for MCL in first remission led to inferior failure-free survival as compared with single-agent ibrutinib (Imbruvica) or the Bruton’s tyrosine kinase inhibitor plus HCT.
Fenske reported primary findings from the EA4151 trial, designed to determine whether HCT benefits patients with MCL in deep first remission. Investigators in the multicenter North American trial determined patients’ MRD status by means of an immunoglobulin high throughput assay with sensitivity of 1 x 10-6.
All patients began treatment with rituximab-containing induction therapy. Those who achieved uMRD status were randomized to autologous HCT plus rituximab for 3 years or to rituximab alone. Patients with detectable or indeterminate MRD status underwent HCT and received 3 years of rituximab.
Data analysis included 650 patients: 516 with uMRD, 49 with MRD-positive status, and 85 with indeterminate MRD status. The futility boundary was an OS hazard ratio of 0.984 for the comparison of HCT plus rituximab versus rituximab alone.
An OS analysis that included all randomized patients yielded a hazard ratio of 1.11. An analysis limited to the 375 patients who actually received assigned treatment produced a hazard ratio of 1.00. The 3-year OS values for the per-protocol analysis were 86.2% with HCT and 84.8% with rituximab alone.
The hazard ratios for 3-year PFS were 1.05 for all patients and 0.95 for the per-protocol analysis. Absolute values were 76.6% with HCT and 77.4% without and 81.5% versus 80.4%.
An exploratory analysis of OS in the MRD-positive patients showed a 3-year OS of 100% with HCT and rituximab in 17 patients who converted to uMRD after transplantation. That contrasted with 63.6% for patients who remained MRD positive. The 17 patients also had a 3-year PFS of 100% versus 48.8% for the patients who remained MRD positive.

Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures
The EA4151 study was supported by the National Cancer Institute.Fenske disclosed relationships with AbbVie, Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, Bayer, BeiGene, Janssen, Kite, Lilly, Ono Pharmaceuticals, and SeaGen.Sekeres disclosed relationships with Bristol Myers Squibb, Kurome, and Schrodinger.

Primary Source
American Society of Hematology
Source Reference: Fenske TS, et al “Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma patients in first complete remission with undetectable minimal disease: Initial report from the ECOG-ACRIN EA4151 phase III randomized trial” ASH 2024; Abstract LBA-6.

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LOS ANGELES — The FDA’s warning about arrhythmia risk with lamotrigine (Lamictal) based on in vitro data wasn’t borne out in observational cohorts of people with epilepsy, although the risk did appear significant in people with bipolar disease.
The difference in findings presented at the American Epilepsy Society (AES) annual meeting appeared to be due to comparator drugs used between the two conditions.
In a study looking at Medicare and U.K. CALIBER datasets for new-onset epilepsy or seizure disorder cases, initial treatment with lamotrigine wasn’t associated with any higher risk of serious ventricular arrhythmias or death compared with levetiracetam as a “presumably cardiac ‘inert'” control, reported Samuel Terman, MD, of the University of Michigan Department of Neurology in Ann Arbor.
In a larger study of Medicare and commercial claims data, lamotrigine didn’t hold any greater ventricular tachycardia (VT) risk compared with other sodium channel blockers or other drugs for the same seizure indications.
However, lamotrigine used for bipolar disorder in that study did have higher VT risk than commonly used antipsychotics (HR 1.243, P=0.02), with an absolute risk difference of about 0.09% at 1 year, reported Przemyslaw Radwanski, PharmD, PhD, of the Ohio State University College of Pharmacy in Columbus.
Neither study showed a significantly greater risk for lamotrigine in patients with comorbid heart disease.
In 2021, the FDA warned about potential increased arrhythmia risk in people with cardiac disease who are taking lamotrigine based on reports of abnormal ECG findings and cases of chest pain, loss of consciousness, and cardiac arrest. Suggesting it could be a class effect, the agency required in vitro safety studies on all the sodium channel blockers, although that data has yet to be made publicly available.
The new observational data add to the AES treatment committee’s prior conclusion that “there’s nothing to this” based on an extensive review, said AES board of directors member David Vossler, MD, of the University of Washington School of Medicine in Seattle.
“When you look at this compared to other antiepileptic drugs, we’re not seeing a clear difference,” he summarized. However, he added, “We will know more when the manufacturers complete their additional in vitro studies.”
“There’s no need to take patients with epilepsy off lamotrigine,” Vossler concluded. “But if they have other significant heart conditions, including structural heart disease or known cardiac arrhythmias, getting an EKG test and perhaps even consulting with a cardiologist would be prudent. But for someone that’s otherwise healthy, I don’t believe you need an EKG or even need to see a cardiologist. And from both of these studies, there’s no evidence of increased risk.”
For the bipolar patients, “the question is maybe lithium, quetiapine [Seroquel], and risperidone [Risperdal] are less problematic than lamotrigine,” he noted. “That’s an observation that needs to be explained.”
With lamotrigine so commonly used for bipolar disorder, even a small increase in risk, if real, would mean serious risk for a meaningful number of patients over the course of a year in the United States, Radwanski argued.
Radwanski’s study used the Merative MarketScan Commercial Claims and Medicare Supplemental Database to find 2.6 million adults with at least one prescription filled for lamotrigine or controls comprising other medications for the same indication. For partial seizure, 10,275 persons on lamotrigine were matched with the same number on carbamazepine, levetiracetam, oxcarbazepine, or eslicarbazepine. For generalized tonic-clonic seizure, 5,855 pairs were matched for lamotrigine versus controls on valproate, levetiracetam, carbamazepine, or zonisamide (Zonegran). For bipolar disorder, 148,645 matched pairs were on lamotrigine versus comparators of lithium, quetiapine, valproate, or risperidone. Individuals with preexisting ventricular or atrial arrhythmia during the 6 months prior to enrollment were excluded.
Onset of VT while covered with one of these medications for at least 7 days during 365 days of follow-up was not significantly more common with lamotrigine in partial seizure patients (HR 1.477, 95% CI 0.886-2.462, P=0.14) or generalized tonic-clonic seizure patients (HR 1.427, 95% CI 0.622-3.271, P=0.40).
Although the statistical significance is limited, “the positive association is ubiquitous across epileptic conditions,” Radwanski concluded, suggesting that the smaller cohorts in those indications might have been underpowered to find small differences.
Terman’s study included a total of 53,652 patients in a Medicare 20% random sample or the U.K. CALIBER study from primary and secondary care practices. Enrollment was limited to adults with epilepsy or seizure diagnoses who were starting lamotrigine or levetiracetam without any antiseizure medication use in the prior year.
After adjusting for a wide range of demographics, comorbidities, and co-medications, 2-year cumulative incidence of VT or ventricular fibrillation in the Medicare group was 0.6 percentage points (95% CI -1.2 to 0.0) less common with lamotrigine than levetiracetam in the intent-to-treat analysis and 0.1 percentage points (95% CI -0.5% to 0.7%) more common with lamotrigine in the per-protocol analysis. In CALIBER, those figures were -0.1 percentage points (95% CI -0.3 to 0.1) and -0.1% (95% CI -0.4 to 0.2), respectively.
Adjusted 2-year cumulative incidence of death was also lower in the lamotrigine groups in each study, by an absolute -7.6% (95% CI -9.4 to -4.8) in the Medicare group and -3.1% (95% CI -2.2 to -4.0) in the CALIBER group.
“Our data support continued use of lamotrigine amongst patients starting a new [antiseizure medication], even amongst those at higher cardiac risk or using concomitant sodium channel blockers,” Terman’s group concluded.
Both studies were limited by their comparators and by the observational nature of the data that could not determine causality or eliminate the potential for residual confounding.

Disclosures
Terman disclosed support from an American Epilepsy Society Research and Training Fellowship for Clinicians and the National Institute on Aging.Radwanski had no disclosures.Vossler disclosed no relevant relationships with industry.

Primary Source
American Epilepsy Society
Source Reference: Terman SW “Lamotrigine and cardiac conduction abnormalities: An international target trial approach” AES 2024; Abstract 2.383.

Secondary Source
American Epilepsy Society
Source Reference: Kim S “Lamotrigine use is associated with ventricular tachycardia: An observational cohort study” AES 2024; Abstract 2.392.

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Canadian public health officials closed their investigation into the teenager who became critically ill with the H5N1 bird flu virus, with no source of infection identified.
It’s not clear whether the teenager recovered or was released from the hospital. Andy Watson, director of communications for the Office of the Provincial Health Officer in British Columbia, said in an email to MedPage Today that the office does not provide patient status updates due to privacy.
The office “won’t be providing any updates on the status of the teenaged patient or this now complete investigation unless there is a need from a public health perspective to do so,” Watson said in the email.
During a press briefing 2 weeks ago, Provincial Health Officer for British Columbia Bonnie Henry, MD, MPH, said the teenager remained in critical care at BC Children’s Hospital in Vancouver. While the individual was stable, they were “still very sick.”
“Our thoughts remain with them and their family and we remain hopeful as they have made some progress in the last few days that they will recover from this very severe infection,” Henry said during the briefing.
Henry said the patient was young and healthy, with no underlying conditions. The infection started with conjunctivitis and progressed over several days to a severe lung infection.
Henry noted that among the 900 cases of H5N1 globally, young people tend to have more severe illness. “It may be that as we get older, we have some exposure to different influenza viruses, particularly with the N1 component, that might give us some protection from severe illness,” she said.
The investigation revealed no additional cases of H5N1 and no evidence of human-to-human transmission, and all testing on human, animal, and environmental samples were negative for H5N1. Public health officials assessed the 60 healthcare workers who had contact with the patient, along with 16 close family and friends, none of whom developed any illness.
A pet dog had been sick at the time of the patient’s onset of illness, but a thorough investigation of the dog turned up no evidence of H5N1 infection, Henry said.
Genetic testing showed the patient was infected with the same H5N1 strain seen in wild birds in British Columbia — clade 2.3.4.4b, genotype D1.1 — and that it most closely matched that of wild birds found in the Fraser Valley area in October. It was not related to outbreaks at poultry farms in British Columbia, Henry added.
However, investigators did see some changes in the genetic sequence that may signal adaptation to humans, and there were some mutations that were particularly concerning, including one that may have led the virus to more easily bind to receptors deep in the lung, causing more severe illness, she said.
Henry said the fact that a source of infection wasn’t found isn’t unusual, as there have been three cases in the U.S. — one in an adult in Missouri, and two in children in California — that don’t have an apparent source of infection.

Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow

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In this exclusive MedPage Today video, Theodore Pak, MD, PhD, of Harvard Medical School in Boston, discusses the findings from a study that examined how changes in masking and testing policies in hospitals influenced rates of respiratory viral infections, including COVID-19, influenza, and respiratory syncytial virus (RSV), during the 2023-2024 season.
Following is a transcript of his remarks:
The impetus for this study is that policies for preventing respiratory viral infections in the hospital setting has obviously changed and evolved a lot since the start of the COVID pandemic. And because of the way the pandemic evolved, we often had to implement these changes on the fly. Many hospital systems were figuring out what to do next. It was very unpredictable.
And I think the point of this study is to look at the trend and particularly the last respiratory viral season from 2023 to 2024 and think about what does that mean for what hospitals should consider going forward in terms of masking of staff, masking of patients and visitors, and also testing all patients upon coming to the hospital.
So just to set this up, we had done a study and published it in JAMA Internal Medicine about a year ago, and that reviewed data from the National Health Service, which spans the United Kingdom, but in particular they release a lot of great public data on hospital-onset and community-onset COVID infections at a nationwide level. So it was a very large dataset.
Our health system decided to end universal testing and also universal masking around the same time in May of 2023. So that was about the time the federal public health emergency was ending as well, and general rates of community COVID and other respiratory viruses were on a downtrend at that point going into the summer. So those policy changes occurred, and we decided to do a similar study.
Now we had our own health system, we could use data where we could dig deep into individual cases if necessary, to look at why is testing being performed for this particular patient, what is the clinical background for each case? And we were looking for a very similar thing. What is the association between that policy change and subsequent rates of hospital-onset respiratory viruses? And in this case, we included COVID, influenza, and RSV before and after that policy change.
The rationale for adding more respiratory viruses like flu and RSV is that, last winter, we actually had more of those cases. Those are picking back up again. And our last winter was basically split pretty evenly between flu and COVID in particular, but with still a decent proportion of RSV cases.
So what we saw was that after this policy change occurred, when universal masking and testing ended in our health system, we saw a rise in hospital-onset respiratory and viral infections compared to the number of patients being admitted for those same kind of infections from the community. In an unadjusted model, the change in the ratio is about a doubling, but for these kinds of studies, you do want to adjust for other factors like seasonality, etc. And after doing that, it’s about a 25%, but significant, increase after ending masking and testing compared to the counterfactual of the same trends continuing from the prior period essentially.
And then we were able to add a fourth study period to this analysis because as winter happened last year, of course rates of respiratory viruses started picking back up in the community, and the health system decided to start targeted masking. And what that means is we would have all healthcare staff mask when interacting with patients. These are surgical masks, but it is at least one layer of protection there. And after that policy change, which started January 2024, we were able to collect about 3 months of data. But we did see, using the same model, a 33% drop in hospital-onset respiratory viral infections relative to community-onset infections.
And so, all this goes to show us these two associations where you pull back on precautions and you see a rise, and then you reinstitute some precautions and you see a drop, that these precautions are really tightly associated with changes in hospital-onset infections, and therefore hospitals should really carefully consider them for the coming winter as, no doubt, all these infections pick up again in the community.

Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams. Follow

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Developments in chronic lymphocytic leukemia (CLL) this year included the first CAR T-cell therapy approval for the chronic blood cancer, potential treatments for Richter transformation, and investigations into triplet regimens.
First CAR-T Approved for CLL
In March, the FDA granted accelerated approval to lisocabtagene maraleucel (liso-cel, Breyanzi) for pretreated CLL or small lymphocytic lymphoma (SLL).
A CD19-directed cellular therapy, liso-cel is the first CAR-T product specifically for CLL/SLL; the one-time infusion is indicated for patients with relapsed or refractory disease following two or more prior therapies, including both a BCL-2 inhibitor such as venetoclax (Venclexta) and a Bruton’s tyrosine kinase (BTK) inhibitor such as ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa).
Findings from the phase I/II TRANSCEND CLL 004 study supported liso-cel’s approval. Among patients with relapsed or refractory CLL/ SLL in the single-arm, open-label trial, 45% responded to treatment, including complete responses in 20%. The median duration of response reached 35.3 months overall and was not reached among complete responders, a group that had high rates of minimal residual disease (MRD) negativity in the blood (100%) and bone marrow (92.3%).
As with other CAR-T drugs, liso-cel includes a boxed warning about the risk for secondary T-cell malignancies, cytokine release syndrome, and neurologic toxicities.
Moving the Needle in Richter Transformation
New studies evaluated treatment options for Richter transformation, a rare complication of CLL/SLL where the leukemia turns into an aggressive lymphoma.
In a subgroup analysis of the BRUIN study — which led to last year’s approval of pirtobrutinib (Jaypirca) in CLL/SLL — half of patients with Richter transformation responded to the oral non-covalent BTK inhibitor.
Of the 82 patients with Richter transformation in the phase I/II study, 13% achieved complete responses and 37% had partial responses. Almost half of the responses lasted a year or longer. Eight patients discontinued pirtobrutinib while still in response to undergo stem-cell transplantation. A majority of patients had grade ≥3 adverse events (AEs), but relatively few patients discontinued treatment because of AEs.
“For a disease with few treatment options, pirtobrutinib offered single-agent activity and, as is often the goal for some patients, a bridge to a potentially curative treatment option,” William Wierda, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues concluded in Lancet Haematology.
“This subgroup with Richter transformation included many heavily pretreated patients, who historically have a poor expected overall survival [OS],” the researchers pointed out. For example, the study population had received a median of two prior therapies for Richter transformation, and three-fourths had prior treatment with a covalent BTK inhibitor.
In the phase II MOLTO study, a three-drug regimen involving a PD-L1 inhibitor and two targeted agents was active and safe for treating the diffuse large B-cell lymphoma variant of Richter transformation.
Among 28 patients previously untreated for their Richter transformation, the overall response rate reached 68% following six cycles of atezolizumab (Tecentriq) plus venetoclax and obinutuzumab (Gazyva), including complete responses in 29%. One-year rates of progression-free survival (PFS) and OS landed at 43% and 64%, respectively.
“The clinical activity of this chemotherapy-free regimen translated into durable remissions and a prolonged survival benefit, making the venetoclax, atezolizumab, and obinutuzumab triplet a potential first-line standard treatment for patients with Richter transformation,” Alessandra Tedeschi, MD, of the Niguarda Cancer Center in Milan, and co-authors wrote in Lancet Oncology.
New Data on Triplets for CLL
A fixed-duration, three-drug regimen for CLL achieved deep and durable remissions lasting for up to 7 years, according to updated results from a prospective study.
Median PFS with ibrutinib, venetoclax, and obinutuzumab exceeded 80 months in patients with untreated or relapsed/refractory CLL. Almost 60% of patients with untreated disease had undetectable MRD (uMRD) status, as did 44% of the relapsed/refractory cohort. Overall response rate at the end of treatment was 88% in patients with previously treated CLL, and 84% and 96% for two untreated cohorts. The study involved 75 patients with CLL.
Interestingly, uMRD status had no association with PFS, reported Kerry Rogers, MD, of the Ohio State University in Columbus, at the 2024 European Hematology Association meeting in Madrid.
“Additional studies are needed to determine the relative benefit of either three- versus two-drug regimens, particularly the inclusion of an anti-CD20 monoclonal antibody, as well as mechanisms of resistance and sensitivity, and, of course, the optimal sequence of treatments over the lifespan of patients with CLL,” she said.
In updated results of another prospective study, time-limited treatment with a similar triplet — acalabrutinib, venetoclax, and obinutuzumab — produced long-term uMRD in more than 90% of patients with relapsed/refractory CLL.
After a median follow-up of 36.3 months, 42 of 45 patients (93%) achieved uMRD in peripheral blood at any time point with the combination. The estimated 3-year OS rate was 94%. Subgroups with uMRD status exceeding 90% included patients previously treated with venetoclax and those with TP53 mutations.
At last follow-up, patients had been off treatment for a median of 21.9 months. COVID-19 was responsible for all three fatal AEs in the study, reported Moritz Fürstenau, MD, of the University of Cologne in Germany, and co-authors in Blood.
Their report also showed that monitoring circulating tumor (ct)DNA in addition to flow cytometry at least doubled early detection of MRD recurrences.
Ibrutinib’s Negotiated Medicare Price
In August, the Centers for Medicare & Medicaid Services (CMS) unveiled the negotiated prices for the 10 drugs selected under Medicare’s drug-price negotiation program — the first-generation BTK inhibitor ibrutinib among them.
Ibrutinib will drop from a list price of $14,934 to $9,319 under the negotiated terms, representing a 38% decrease. The new prices will take effect beginning in January 2026.
The price negotiation program was passed in 2022 as part of the Inflation Reduction Act. The measure lowers prescription drug costs for seniors by empowering Medicare to negotiate the cost of prescription drugs for the first time. The 10 drugs chosen for negotiation by CMS — single-source brand-name drugs with no therapeutically equivalent generic or biosimilar competition — were targeted for negotiation based on their total expenditures in the Medicare Part D program. These drugs are either costly, widely used, or both. Costs for ibrutinib in 2023 totalled $2.37 billion for the 17,000 enrollees who used the drug.
Other drugs on the list include blood thinners and therapeutics for diabetes, heart failure, chronic kidney disease, rheumatoid arthritis, inflammatory bowel disease, and psoriasis.
New Labeling for Fludarabine
In November, the FDA updated drug labeling for fludarabine as part of its Project Renewal program, an initiative that aims to make sure the prescribing information for older oncology drugs remains clinically meaningful and up to date.
Fludarabine’s labeling now reflects that the chemotherapy can be used for adults with B-cell CLL in combination with cyclophosphamide and rituximab, and as monotherapy for those who have failed on a prior regimen containing an alkylating agent.
In addition, a previous boxed warning regarding central nervous system toxicity, hemolytic anemia, and pulmonary toxicity was removed and the information was moved to the label’s “warnings and precautions” section.
Senior Editor Charles Bankhead and Washington Editor Joyce Frieden contributed to this report.

Ian Ingram is Managing Editor at MedPage Today and helps cover oncology for the site.

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When Matt was diagnosed with ALK-positive (ALK+) metastatic non-small cell lung cancer (mNSCLC), his world turned upside down. It’s a moment that many patients like Matt dread — the words “you have cancer” hang in the air, bringing with it waves of fear and uncertainty. For Matt, a Stage 4 diagnosis meant facing an uncertain future. His wife, a nurse, grasped the severity more than he did, while Matt was still coming to terms with what his diagnosis meant.
“I didn’t know what to expect,” Matt recalls. “My wife understood it better than I did, but for me, it was like, ‘Okay, I have cancer — what now?'”
The “what now” led Matt to Alecensa® (alectinib), a treatment that has helped to redefine what it means to live with an ALK+ mNSCLC diagnosis. Alecensa has been available as a treatment option for patients like Matt since it was first approved in 2015 for metastatic ALK+ NSCLC. It was later extended to some earlier stages of the disease, when it was approved in 2024 for treatment after surgery, or adjuvant therapy.1
A New Normal for Matt
When Matt started Alecensa, his mindset began to shift. “Even though I’m a Stage 4 cancer patient, I don’t feel like one,” Matt notes. “I take the Alecensa pills in the morning and at night. It has become part of my new normal.”
For Matt, Alecensa wasn’t just a cancer treatment; making the informed decision to start Alecensa with his physician gave him a sense of control in a situation that often feels uncontrollable. “Starting treatment brought a new sense of hope,” he shares, reflecting on the positive changes he felt soon after beginning Alecensa.
Alecensa has proven its superiority over another ALK inhibitor in extending progression-free survival. In the Phase III ALEX study, Alecensa significantly reduced the risk of disease worsening or death by 47% (HR=0.53, 95% CI: 0.38, 0.73, p

Young is a family medicine physician and nocturnist.

I am torn. I have the devil whispering in one ear, telling me to join with the masses hailing the murder of UnitedHealthcare CEO Brian Thompson and shouting that he had it coming to him. And I have the angel speaking in my other ear, reminding me that physicians must rise above violence and hate. A man is dead after all.
So, where do we go from here?
On the one hand, I shed no tears for Thompson. The man made millions off the suffering of others. More than $10 million last year, in fact. Likewise, every penny of the $22 billion in profit made by parent company UnitedHealth Group in 2023 was at the expense of the suffering of others.
I have no small amount of schadenfreude for what has happened to him. Sometimes, I even find myself wanting to crack jokes at his expense. Is Hell going to require a 2-night qualifying stay prior to admission? Does he have a skilled demonic need that would merit admission to Hell? Others have had similar reactions, posting online comments like, “Unfortunately my condolences are out-of-network,” and “Prior authorization is needed for thoughts and prayers.”
As physicians, I understand how easy it is to sit back and take some pleasure in the death of a man whose leadership of an insurance company led to the untold suffering of hundreds of thousands of our patients. Patients we care for every day.
Yet, I am torn. This guy was my age (he was 50 years old, and I’m 49). He has a wife with two kids. His kids are 19 and 16 years old, near the same age as mine (in their teens). They’ve gotten bomb threats to their home. When they look on social media, they see nothing but hate directed at the man they loved — a man they called their husband, or Dad.
I hate everything that Thompson stood for. I hate everything that his company stands for and will likely continue to stand for. I expect that the UnitedHealth Group PR and legal teams will use his death as an excuse to stifle any substantive debate or legitimate criticism about UnitedHealthcare with the mantra of, “We need to cool the temperature of the conversation,” or some similar, hollow PR statement.
And yet, I find myself troubled by jumping on the bandwagon of hate.
Thompson was a human being, and we as physicians are supposed to have compassion for all. We are to care for all — saints or sinners, good or bad, demonic or angelic. What they do or did is irrelevant. We treat murderers, rapists, and politicians alongside charity workers, victims of crime, and the saintly. What allows us to do that is the compassion we have for people. It’s what keeps us in this profession, despite the machinations of companies like UnitedHealthcare and people like Thompson, and whatever corporate leader rises to replace him.
So, what I’m calling upon us, as physicians, to do is to remember that we are the adults in the room. We are the profession that has the moral high ground opposite companies like UnitedHealthcare and people like Thompson. We are supposed to be better.
We need to take this opportunity to mourn the loss of another human being, taken by violence on our streets. We need to show compassion to his family.
We need to say with a single voice that we condemn the actions of Thompson and UnitedHealthcare as vehemently as we condemn the actions of his assassin. We need to warn that too many people — both patients and executives — will continue to suffer until insurance giants put the needs of the patient above those of the shareholder. While I don’t condone more killing or violence against health insurance executives, it’s not unlikely. In fact, it’s already happening. But it needs to be made clear that it’s not rhetoric or debate about insurance company malfeasance driving this action, but the companies’ own actions.
We as physicians need to be vocal, engaged, and seize this moment where the public is now engaged and the media watching, to make the case for why insurance in America is broken. We must also be above the fray.
So, while I hate UnitedHealthcare and Thompson’s policies, I mourn his death as I would mourn any death, and I truly feel deeply for the loss and pain that his family must be feeling at this moment. I put them in my prayers and I hope that healing, albeit slowly, does eventually come to them. I also pray that health executives everywhere use this as a moment to not only beef up their security but also to ask, “Why?”
James Young, MD, is a family medicine physician and a nocturnist at Marshfield Clinic Hospital in Eau Claire, Wisconsin. His opinions are his own and do not necessarily reflect any organization or company with which he is affiliated.

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Empathy-oriented phone calls from laypersons helped patients with uncontrolled diabetes improve glycemic control, a parallel-arm superiority trial found.
Among 260 participants, those who received calls from community-hired laypeople decreased their HbA1c from 10% to 9.3% by 6 months. Meanwhile, HbA1c in the usual care group held steady from 9.8% to 9.7%, reported Maninder Kahlon, PhD, of the University of Texas at Austin, and colleagues.
The impact of the phone calls was even more pronounced in patients with baseline scores of 5 or higher on the depressive symptoms scale of the 9-item Patient Health Questionnaire (PHQ-9). For this subset, patients who received the phone calls had an HbA1c drop of 1.1% (95% CI -1.8% to -0.5%) compared with a 0.1% (95% CI -0.7% to 0.8%) increase for controls.
These HbA1c reductions were “on the higher end of improvements previously seen” in other trials that used psychological interventions such as cognitive behavioral therapy or motivational interviewing, the researchers wrote in JAMA Network Open.
While behavioral health support is known to be beneficial for patients managing diabetes and comorbid depressive symptoms, it carries barriers to access, and “when available, is offered only for those who reach a clinical threshold, with an insufficient workforce severely limiting capacity, particularly for patients with low socioeconomic status who lack resources,” the researchers said.
The approach in this trial was different from prior models that instead shifted focus back to the needs of the patient on their own terms.
“The goal was not to accomplish tasks but to converse to learn more about the patient,” said Kahlon’s group. “Patients chose the frequency and length of calls and discussed their own interests.”
Throughout the 6-month trial, participants received calls of unlimited duration from a bilingual dedicated caller. Callers didn’t have a healthcare background — just 8 hours of training — and discussed the participant’s life with diabetes. They didn’t stick to a script, and instead asked questions about whatever the patient raised themselves, whether it be dinner or frustrations with management blood glucose.
“When they expressed needs, which they were more likely to do because they were being called regularly by someone they trusted, patients were supported in connecting back to the health system,” said Kahlon and co-authors. “This reversal of focus, starting with the patients on their own terms, may have increased their sense of autonomy, enabling healthy lifestyle changes aligned with personal preferences.”
Participants received three telephone calls in the first week from their assigned caller and then chose one to five calls per week for the next 3 weeks, and subsequently one call every 1 or 2 weeks. On average, 20 calls were completed per participant in the intervention group and call duration was 360.6 minutes total.
In addition to the calls, participants were also mailed two gifts, worth less than $25 each, selected by callers that reflected their understanding of participants’ preferences, such as a yoga mat or a cookbook.
In an invited commentary, Brett Thombs, PhD, of Jewish General Hospital in Montréal, Canada, and colleagues called the program “unique,” and said the outcomes indicated that social support is a “critical ingredient” in helping people with diabetes improve glycemic control.
“Indeed, this would be consistent with considerable evidence that links social support, defined as the perception or reality that one is cared for and has assistance available from others, to positive health behaviors and outcomes,” they wrote.
Additional studies should try to replicate the findings, Thombs’ group suggested, since this simple intervention “could expand our ability to provide needed support in diabetes and other conditions.”
Participants were recruited via text messages from a federally qualified health center (FQHCs) in Austin, Texas — 129 were randomized to the intervention and 131 to the control. FQHCS are federally funded centers that offer primary care to medically underserved populations regardless of patients’ ability to pay.
Most participants (78.5%) were Hispanic or Latino, 62.9% were female, and average age was 49.5. Nearly 87% had an annual income under $40,000. All had uncontrolled diabetes defined as at least 1 HbA1c measurement of 8.0% or greater at a clinic appointment in the prior 12 months with an HbA1c measurement of 7.5% or greater at trial enrollment.
After 6 months, 91.7% of participants who received phone calls said the program was “very” or “extremely beneficial.”
Even those with baseline PHQ-9 scores less than 5 had a benefit. In this subset, the intervention group had a significant 0.4% drop in HbA1c compared with a nonsignificant 0.02% drop for the control group.
The trial was limited by the somewhat short 6-month follow-up period. Kahlon’s group said it would be “useful” to see the benefits of a longer duration program or whether glycemic impacts are sustained long-term.

Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures
The study was supported by the Episcopal Health Foundation in Houston.Kahlon disclosed support from the Michael & Susan Dell Foundation and the United Health Foundation, as well as being a founder of a Texas LLC with an active Medicaid contract. Co-authors disclosed relationships with Sandoz, Johnson & Johnson, and 3M.Thombs disclosed support from a Tier 1 Canada Research Chair.

Primary Source
JAMA Network Open
Source Reference: Kahlon MK, et al “Glycemic control with layperson-delivered telephone calls vs usual care for patients with diabetes – a randomized clinical trial” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.48809.

Secondary Source
JAMA Network Open
Source Reference: Thombs BD, et al “Layperson-delivered interventions for glycemic control in diabetes” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.48740.

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LOS ANGELES — An artificial intelligence (AI) model accurately detected and ruled out infantile epileptic spasm syndrome in videos captured by family, a study showed.
The model had an area under the receiver-operating-curve (AUC) of 0.96, with 82% sensitivity and 90% specificity, reported Gadi Miron, MD, of Charité-Universitätsmedizin Berlin in Germany, at the American Epilepsy Society annual meeting. The results were simultaneously published in a medRxiv preprint.
Validation on external datasets from smartphone videos yielded a similar AUC of 0.98 with a false positive rate (FPR) of 0.75%, as did comparison to gold-standard video-EEG (AUC 0.98, FPR 3.4%).
The tool has great promise if further developed into a simple, rapid screening tool for families or physicians to use, commented Deborah Holder, MD, of Cedars‑Sinai Children’s Health Center in Los Angeles.
“When babies have this diagnosis, we consider it a neurologic emergency, so anything we can do to make a fast diagnosis and get these babies to medical treatment is really important,” she told MedPage Today.
Delayed diagnosis is common due to misrecognition of symptoms and can lead to long-term cognitive problems, Miron agreed.
The idea came from a trove of YouTube videos of potential epileptic spasms that parents had posted asking, “‘What is this? Who can help me?'” Miron said. “There’s a very active community of these parents trying to help each other out, and the clinical need is just basically coming from that.”
Pediatricians and primary care physicians are often presented with these videos recorded by parents, since the events can come in clusters, allowing parents time to catch them on video. “They don’t always happen when you go to the doctor’s clinic, and then the parents need to describe and it’s much harder to understand and to recognize what’s happening,” Miron noted.
If the doctor has a relationship with a neurologist or epilepsy specialist, the videos typically then get sent for a quick screen, noted Holder, who says she receives such videos every day. Otherwise, families have to wait for a clinic visit, which adds to the delay.
“There are not a lot of us around to look at them individually,” she said. “There are whole areas of the country where there’s just resources that aren’t available. So to be able to help the primary care docs have better access to the expertise, and if there’s computer programs that can be trained to look at these videos, it’s very cool and very exciting. We just want to make sure that it’s in the hands of the people who know how to use it and get the patients where they need to be.”
Miron agreed that deployment will be key.
“This is still in the research stage, but I think it shows a lot of promise, because we have addressed some of the issues that are important in order for it to be clinically transferable,” Miron said. “Of course, in order to be clinically applicable, it needs to be validated further prospectively in additional datasets. It needs to be matched with some type of tool that the parents can use.”
His group built an app and a doctor’s platform and are testing them in the clinic and emergency department in a prospective single-center study, with hopes to expand to other centers as well, he said.
His group trained the AI model on a YouTube video from 141 children with 991 seizures, found by searching for “epileptic spasms,” “infantile spasms,” and “West syndrome,” compared with video from 127 children without seizures.
These were validated against two cohorts sourced from smartphone videos: 26 infants with seizures (70 seizure and 31 non-seizure 5-second video segments) and 67 infants without seizures. Validation against in-hospital video-EEG monitoring, included 21 infants without seizures to look for a false alarm rate.
“Videos demonstrate high heterogeneity in resolution, bit rate, brightness, and sharpness,” Miron’s group noted. “Our model performs well on multiple datasets, exhibiting robustness across camera sources and technical heterogeneity. Future studies should focus on validation, translation, and clinical application.”

Disclosures
The study was partially funded by a grant from the Berlin Institute of Health.Gadi and Holder disclosed no relationships with industry.Co-authors disclosed patent applications related to neurological conditions outside the study, and relationships with Angelini, Bial, Desitin, Eisai, Jazz Pharma, Neuraxpharm, Nutricia, and UCB.

Primary Source
American Epilepsy Society
Source Reference: Miron G, et al “Detection of epileptic spasms using foundational AI and smartphone videos: A novel diagnostic approach for a rare neurological disorder” AES 2024; Abstract 1.179.

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