View previews and the latest developments from Digestive Disease Week, being held in San Diego and virtually, including session summaries, poster write-ups, and interviews with key opinion leaders.

Coverage of Digestive Disease Week 2022

View news from Asembia’s 2022 Specialty Pharmacy Summit, in Las Vegas, including session summaries, poster write-ups, and interviews with key opinion leaders.

Coverage of AXS22

Julia is an associate editor of The American Journal of Managed Care

since 2022 after receiving her Bachelor's degree at Rutgers University–New Brunswick in English and Creative Writing.

Pulmonary hypertension (PH), which is associated with high mortality, was found to be more common in patients with chronic obstructive pulmonary disease (

) who were referred for a right heart catheterization (RHC), according to a study published in 

The study was conducted using data extracted from the University of Vanderbilt’s Synthetic Derivative database, which is a deidentified version of Vanderbilt’s electronic medical record. All patients who underwent RHC between 1998 and 2017 were identified. All patients needed to be 45 years and older to be included in this study to increase specificity for COPD;   indeterminate status of COPD disqualified a patient from participating. 

A total of 1509 patients with COPD were included in this study. PH was prevalent in 80% of patients with COPD, but this decreased to 66% when applying the historical mean pulmonary artery pressure (mPAP) cutoff of at least  25 mm Hg.

Patients with COPD-PH were younger and had a higher body mass index (BMI), compared with patients with COPD without PH; were more likely to be Black; and had a higher prevalence of diabetes, atrial fibrillation, and heart failure than patients with COPD without PH.

The risk of death was increased in patients with COPD-PH compared with patients with COPD (HR, 1.70; 95% CI, 1.28-2.26) when adjusting for age, sex, and race. Patients with COPD-combined postcapillary and precapillary-PH had the highest risk of death (HR, 2.39; 95% CI, 1.64-3.47) vs patients with COPD alone. COPD-precapillary-PH (HR, 1.92; 95% CI, 1.22-3.02) and COPD-isolated postcapillary-PH (HR, 1.60; 95% CI, 1.16-2.22) had similar increased mortality risk.

Elevations in risk of death were also found in patients with COPD-PH defined as mPAP of 21 to 24 mm Hg with pulmonary vascular resistance greater than or equal to 3 WU or mPAP of 25 to 34 mm Hg and COPD with severe PH as mPAP of at least 35 mm Hg or mPAP greater than or equal to 25 mmHG with low cardiac index. COPD-PH had a 61% increased mortality risk (HR, 1.61; 95% CI, 1.20-2.21) whereas COPD-PH severe had a 106% greater risk (HR, 2.06; 95% CI, 1.50-2.82).

Patients with COPD-PH referred to RHC had higher right atrial pressure, reduced right ventricular function, increased left atrial diameter, and decreased stroke volume and PA oxygen saturation compared with patients with COPD alone.

There were some limitations to this study. It was conducted at a single center,  the selection of patients with only RHC data may have led to subgroup bias, exercise testing was not performed during RHC but could have increased the number of patients with PH in the study, and treatment options and guidelines for COPD changed in the 17 years that the study took place and could not be accounted for. Using Global Initiative for Chronic Obstructive Lung Disease criteria to determine COPD in patients also likely increased specificity for COPD but sacrificed sensitivity, as it is likely some patients who were deemed indeterminate had COPD.

The researchers concluded that PH is common in patients with COPD who are referred for RHC. They also concluded that PH is often associated with multimorbidity and high mortality, which have implications for risk factor management.

“These results support an integrated approach to objectively identify both diseases at an early stage and to optimize control of respiratory and cardiovascular conditions. Additional studies providing new data on the pathogenesis and management of patients with COPD and PH are needed,” the authors wrote.

Cook DP, Xu M, Martucci VL, et al. Clinical insights into pulmonary hypertension in chronic obstructive pulmonary disease. 

Articles

A recent study found that patients who were referred for a right heart catheterization and had chronic obstructive pulmonary disease (COPD) more commonly had pulmonary hypertension, which is associated with high mortality.

Pulmonary Hypertension Common in Patients With COPD Referred for Catheterization, Study Finds

The short-term survival of adolescent and young adult (AYA) 

 survivors has improved over time, but long-term mortality outcomes are not as clear. A 

Cancer Epidemiology, Biomarkers & Prevention

 aimed to provide insight into long-term outcomes and found that these patients have higher mortality rates than the general population, even decades after diagnosis.

The population of AYA (aged 15-39 years) cancer survivors has grown in the last few decades due to increased rates of cancer in AYAs and better 5-year survival rates as treatments have improved. Two of the most common cancer diagnoses in AYAs are acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), and 5-year survival for these cancer types decreases with age.

The current study explored the long-term survival patterns of AYA leukemia survivors and assessed demographic factors that may contribute to long-term survival based on data from the Surveillance, Epidemiology, and End Results (SEER) registry. A total of 1938 ALL 5-year survivors and 2350 AML 5-year survivors diagnosed between 1980 and 2009 were included in the study, with a median diagnosis age of 23 years in ALL and 28 years in AML. Median follow-up times from diagnosis were 12.3 years in ALL and 12.7 years in AML, and an accelerated failure time model was used to determine the effect of age at diagnosis, patient characteristics, and decade of diagnosis on long-term survival.

Overall, AML and ALL patients had similar survival, but both cohorts had lower survival compared with the general population. While the 10-year survival rate in the general population was 99%, AML survivors and ALL survivors has 10-year survival rates of 89% and 87%, respectively. At 30 years of follow-up, AYA leukemia survivors still showed lower survival rates than the general population.

Older age at diagnosis was associated decreased long-term survival in both groups, and male AML survivors survived 61% as long as females (95% CI, 0.45-0.82). The same difference between male and female survivors was not seen in ALL.

Over time, the length of survival for AYA leukemia survivors more than doubled, with patients diagnosed in the 1990s and 2000s living twice as long compared with patients diagnosed in the 1980s. In earlier decades, the leading cause of death in early survivorship was acute leukemia in both ALL and AML patients. But deaths due to acute leukemia eventually plateaued, and non-leukemia deaths in AYA leukemia survivors became more common than acute leukemia deaths at approximately 20 years of follow-up.

“Importantly, treatment advances leading to increased cure rates and improvements in supportive care, specifically for patients receiving stem cell transplants, have improved survival for AYA patients with leukemia diagnosed in more recent decades,” the authors wrote.

The authors noted that while past research has identified ethnic and socioeconomic status (SES) disparities in survival, this study did not produce statistically significant findings in that regard. Adjusting for SES and a limited cohort size may have to do with the lack of findings regarding either SES or ethnic disparities in this study, the authors wrote.

Overall, the findings suggest there is still work to do to improve long-term survival in AYA leukemia patients.

“While there have been improvements in late mortality, long-term survival for AYA leukemia survivors remains below that of the general population,” the authors concluded.“ Studies investigating risk factors for mortality and disparities in late effects among long-term AYA leukemia survivors are needed.”

Berkman AM, Andersen CR, Cuglievan B, et al. Long-term outcomes among adolescent and young adult survivors of acute leukemia: a surveillance, epidemiology, and end results analysis. 

 Published online May 13, 2022. doi:10.1158/1055-9965.EPI-21-1388

While 5-year survival in adolescent and young adult leukemia has improved in recent decades, this patient population still faces increased long-term mortality compared with the general public.  

 

Adolescent, Young Adult Leukemia Survivors Face Higher Long-term Mortality Rates

 gives a novel perspective on the similarities between pulmonary chronic 

 (cGVHD) and chronic lung allograft dysfunction (CLAD) and informs where more research is needed.

Although allogeneic hematopoietic stem-cell transplantation (HSCT) is a potentially life-saving treatment for patients with hematological conditions, cGVHD can limit long-term survival post transplant. Similarly, long-term survival following lung transplantation can be limited by CLAD.

Most organs can be affected by cGVHD, which occurs in an estimated 30% to 70% of patients after HSCT. Pulmonary complications of cGVHD, potentially including bronchiolitis obliterans syndrome and forms of restrictive interstitial lung disease (ILD), can have a significant impact on morbidity and mortality after HSCT.

Lung transplantation is a well-established option for patients with end-stage lung disease, but despite progress in transplant donor selection and surgical and aftercare management, CLAD still remains a complication—affecting about 50% of transplant recipients within 5 years of their operation. Bronchiolitis obliterans syndrome and restrictive allograft syndrome, which typically involves ILD, are the 2 main clinical types of CLAD. A third subtype is a combination of the features of the 2 main types.

Post-HSCT pulmonary cGVHD and CLAD after lung transplantation have similar underlying immunopathology leading to pulmonary fibrosis and structural lung remodeling, although more research has been done on CLAD due to its prevalence and mortality rates. The present study’s authors argue that a better understanding of both conditions is necessary to diagnose them early and improve treatments and outcomes.

Immunosuppressive regimens are typically used to treat cGVHD and CLAD, but those also come with risks and have thus far struggled to prevent and treat both conditions. Overly aggressive immunosuppressive therapy can also lead to a reduction in the potentially curative graft-versus-host effect meant to occur after HSCT for hematological conditions. Immunosuppressive regimens also increase a patient’s risk of infection when used in any context, including cGVHD or CLAD. More in-depth research on the underlying mechanisms of both conditions could help clarify the causes of disease onset and progression, allowing for more strategic treatment of at-risk patients.

Bronchiolitis obliterans syndrome is the only condition technically recognized as pulmonary cGVHD, and there are significant similarities between bronchiolitis obliterans syndrome seen after HSCT and after lung transplantation. Despite varying clinical backgrounds or triggers, they have similar processes of tissue remodeling and gene expression of fibrosis-related genes.

Progressive obstructive airflow limitation, assessed by pulmonary function tests (PFTs) such as spirometry, is the main clinical diagnosis tool for bronchiolitis obliterans syndrome. However, the authors highlight difficulties with this methodology, including the potential for missing the clinical features until the disease is advanced because bronchiolitis obliterans syndrome is a small airways disease. Increased screening frequency and estimating PFT trajectories may help in this regard.

ILD after lung transplantation has long been considered a potential complication, and restrictive allograft syndrome has been recognized as a separate entity since 2010. The umbrella term CLAD was introduced to cover both obstructive (bronchiolitis obliterans syndrome) and restrictive (restrictive allograft syndrome) lung allograft dysfunction. However, in pulmonary cGVHD, there is no official recognition of a restrictive phenotype. This, the authors note, is a significant gap that needs to be addressed to provide clear clinical guidance on diagnosis and management.

A chest CT can reveal manifestations of restrictive allograft syndrome in patients with CLAD, revealing features like ground-glass opacities and signs of tissue fibrosis. CT imaging could also prove useful in identifying ILD in restrictive pulmonary cGVHD, considering the 2 conditions show comparable radiological findings.

Effective therapies for prevention and treatment of CLAD represent an unmet need for patients undergoing lung transplant, and more research is necessary to determine effective treatments and improve long-term patient survival. Current options have varied efficacy, and the adverse effects of currently available options directed against immune response limit their use.

In pulmonary cGVHD, the need for effective therapies is even more urgent. Given its rarity, lack of guidelines, and the potentially multisystemic nature of GVHD overall, it is challenging to pinpoint the best therapy options. Preemptive immunosuppressant therapy, an option in CLAD, is not suggested in cGVHD after HSCT due to the risk of hematological relapse from immune response suppression. And even though several new therapies are under investigation, this represents another area where more research is warranted.

Overall, the study authors conclude that each entity could benefit from research on the other, considering the similarities between their mechanisms and clinical characteristics.

“Research efforts should focus on identifying common targets for prevention and treatment, which are an urgent unmet need and might equally benefit both entities, to further improve quality of life and long-term survival after allogeneic HSCT and lung transplantation,” they concluded.

Bos S, Beeckmans H, Vanstapel A, et al. Pulmonary graft-versus-host disease and chronic lung allograft dysfunction: two sides of the same coin? 

. Published online May 2, 2022. doi:10.1016/S2213-2600(22)00001-7

Fine-tuning clinical phenotypes and identifying effective treatments remain challenging in chronic lung allograft dysfunction (CLAD) after lung transplantation and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation. 


CLAD, Pulmonary GVHD Have Similar Clinical Traits, Research Needs

For adolescent girls and young women in South Africa at risk of contracting 

, Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS)–like interventions were associated with favorable behavioral outcomes such as less-risky sexual behaviors, according to a study published 

The DREAMS program was launched by the US President's Emergency Plan for AIDS Relief in December 2014 with the goal of significantly reducing new HIV incidence among adolescent girls and young women in Haiti and 15 sub-Saharan Africa countries. In these areas, women in these age groups are between 2 and 14 times more likely to contract HIV than their male counterparts.

Investigators used the term “DREAMS-like interventions” to capture all HIV prevention initiatives occuring in the study period because they could not distinguish between interventions that were part of the DREAMS program and other, similar interventions put in place by governments or other programs.

The study also reported more exposure to DREAMS-like interventions such as school-based HIV prevention among high school– and college-aged females compared with other forms of interventions involving parents or caregivers, as well as social protection and postviolence care.

However, the authors found no association between exposure to DREAMS-like interventions and HIV status.

“There was evidence of an association between layered interventions and favorable behavioral outcomes, but further research is needed to assess the beneficial aspects of layering HIV interventions to support the sexual and reproductive health of adolescent girls and young women,” the study authors said.

To come to these findings, the authors conducted a cross-sectional survey including 18,296 female participants in South Africa aged between 12 and 24 years, with a median (IQR) age of 19 (15-21) years. With a total of 10,642 households between the Gauteng province and KwaZulu-Natal province, a parent or caregiver at each household was also interviewed.

According to the survey, approximately half (49.9%) of participants said they engaged in sexual activity, and 48.1% of those participants said they used a condom during their most recent sexual encounter.

The survey also revealed higher HIV prevalence in the KwaZulu-Natal province (15.1%) compared with the Gauteng province (7.8%). Further, women aged between 20 and 24 had the highest HIV prevalence for any age group, with a prevalence of 23.9% in the KwaZulu-Natal province and 12.3% in the Gauteng province.

Regarding HIV intervention, 17.6% of participants said they were not exposed to any interventions, while 43.7% were exposed to at least 3 interventions.

There were also varying rates of access to different types of interventions. DREAMS-like interventions such as school-based HIV prevention (63.2%) and HIV testing (51.5%) had much higher uptake than social protection (5.0%), parental or caregiver intervention (0.8%), or postviolence care (1.2%).

Additionally, those who were exposed to at least 3 interventions were more likely to have been tested for HIV (adjusted odds ratio [AOR], 2.39; 95% CI, 2.11-2.71; 

< .001) and to have used condoms consistently in the past 12 months (AOR, 1.68; 95% CI, 1.33-2.12; 

< .001) compared with those who did not access any interventions. However, the rate of condom use was still generally low.

“Layering also appeared to have a greater effect size than exposure to only 1 intervention,” the authors found. “Although the cross-sectional design precludes interpretations of causality, the findings of this study suggest that layered HIV interventions may be a useful strategy for supporting the sexual and reproductive health of adolescent girls and young women.”

As this research only reflects areas where the DREAMS program was implemented and was based on self-reported data, the authors noted the results should be interpreted with caution and require further research.

Govender K, Beckett S, Reddy T, et al. Association of HIV intervention uptake with HIV prevalence in adolescent girls and young women in South Africa. 

 2022;5(4):e228640. doi:10.1001/jamanetworkopen.2022.8640

Adolescent girls and young women in South Africa were more likely to practice favorable sexual behaviors if they accessed DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe)–like interventions such as school-based HIV prevention and HIV testing.

DREAMS HIV Interventions Linked to Favorable Behavioral Outcomes Among Young Women in South Africa

Matthew is an associate editor of The American Journal of Managed Care® (AJMC®). He has been working on AJMC® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

 (AD) is proportionally higher in Black children and socioeconomic-related factors have been considered to play a large mediating role in the development and management of the disease in the clinical setting for this population, said Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University Health Sciences Center.

Diversity has been cited as a major issue in dermatology clinical trials. Can you discuss challenges that contribute to these disparities and potential solutions?

That's a great question. The prevalence of AD is proportionally higher in African American children. We don't really know why that is, it may be because their access to medications, their access to specialty care is more limited. Also, family support can play a giant role in that. Having lots of other children or child care issues can play a role because AD is a very labor intensive disease, especially when you're talking about topical therapy. Transportation, there's all kinds of issues that get in the way of taking care of children who are of limited socioeconomic status.

So, in my practice, about 60% of my patients are Medicaid insured, about 50% of children in the global population are [on] Medicaid insurance. So, again, lack of access to different medications with limited insurance formularies and lack of access to subspecialty care, I think play a major role in that health care disparity. We don't know if there's anything intrinsic about African American or Black skin. We know that the barrier function tends to be a little bit better compared with White skin if you're just looking at parameters like transepidermal water loss after tape stripping, but we don't have a really good idea after that.

We also know that African American children are more susceptible to certain kinds of infections like tinea, for example. That's not one that I mentioned with their relative cutaneous energy, but that's one that can be pretty widespread in children who have AD, and occult tinea capitis is almost endemic in the urban African American population.

I was talking to a caregiver the other day about an African American patient of mine, just trying to get a handle on issues related to poor adherence or why this child has such bad disease. And they were taken care of in a clinical setting where they had been attending primary care visits, but they had a different practitioner every time because it was in a clinical setting. But without much even for that particular family in the way of no shows, we do know that poor adherence to attending clinic visits is higher in the population with low socioeconomic status.

So, all of these things make it much harder to take care of children in that patient population. And so it's not necessarily what their Fitzpatrick skin type is or having dark skin, but socioeconomic status plays a giant role.

I think to help that it would be very useful to be able to have access to social workers and case managers to just help people get to their appointments, remember their appointments, and get access to their medications when they can't get access otherwise. It's very time consuming and difficult for parents of children with moderate to severe disease who have lower health literacy and then a lot of other limitations to access to care and access to medications.

Videos

Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University Health Sciences Center, explains the impact of socioeconomic status on the management of atopic dermatitis in the clinical setting.

Dr Elaine Siegfried Discusses Skin Color, Socioeconomic Implications of Atopic Dermatitis Management

The 2022 Greater Philadelphia Business Coalition on Health (GPBCH) Annual Conference will overview a broad range of topics centered on how employers can get better value for their health benefits spend and generate enhanced population health for their workforce and community, said Neil Goldfarb, president and chief executive officer of GPBCH.

Can you discuss the theme of the 2022 GPBCH Annual Meeting?

The title of the conference this year is, “

Pushing Past the Pandemic: Doing Business Differently to Achieve Health & Value

.” To shorten that, I would just say the theme is really, "how can we innovate to create better value?"

This is a conference primarily designed for employers, as well as the people who work with employers, like benefits consultants and service vendors, to talk about the most innovative current strategies that employers can implement that will help them get better value for their health benefits spend, as well as generate better population health for their workforce and their community.

What lessons do you hope audience members gain from the in-person meeting?

I hope that everybody in the audience, whether it's an employer or another health care system stakeholder, comes away with at least one good idea of something they could be doing differently to drive health and value. We've got a very broad ranging set of topics and speakers on the agenda. We're covering important issues like health equity, innovation on the health plan side, how do you deal with high cost claimants, what are the implications of the Consolidated Appropriations Act (CAA) for employers, where the CAA has major reporting requirements that create a new burden for employers to demonstrate their fiduciary responsibility.

So, I think we have something for everyone here. We also have the winners of this year's health benefits innovation awards, a program we started several years ago. And so employers will be hearing from other coalition members about very innovative strategies that they have undertaken that they believe are delivering better value, and that we believe could be implemented by a broader range of employers throughout our region.

There is a great opportunity at the conference for employers and stakeholders to network with each other. We've built in extra time on the agenda for people to get to know each other, to see old friends, make new friends. And also we have nearly 20 exhibitor vendor sponsors, and these are companies that are doing some very innovative things to support the employer as a customer. So, we have built in a lot of time for attendees to meet with these exhibitors and hopefully learn about some of the new strategies that are being put in to help employers achieve greater value.

Neil Goldfarb, president and chief executive officer of Greater Philadelphia Business Coalition on Health (GPBCH), provides an overview of the core discussion points and other aspects in-person attendees can look forward to at the 2022 GPBCH Annual Conference.

Neil Goldfarb Previews Theme, Potential Takeaways of 2022 GPBCH Annual Conference

Sharon Phares, PhD, MPH, chief scientific officer of the National Pharmaceutical Council, explained the importance of taking other factors in addition to gender into consideration when making health care decisions, marking Women's Health Month.

How well do health technology assessments currently take into account gender differences? How can it be done better?

Currently, gender differences are not looked at very often only when they are specific to a therapy. So, for instance, if you're looking at a therapy for breast cancer, although men can get breast cancer, they're less likely to. But how they could do it differently is to really look at differences by groups. Do women get impacted the same as men and is the value the same? Similarly, it can be said for other groups, not just men and women, but also people of color, people of different ethnicities, etc, to kind of look at those combinations of gender and racial or cultural identity, as well as some issues around things like socioeconomic status, which can impact the value, so to speak, of a medication for a certain group.

Sharon Phares, PhD, MPH, chief scientific officer of the National Pharmaceutical Council, explained the importance of taking multiple factors into consideration when making health care decisions.

Dr Sharon Phares Lists the Many Factors Physicians Should Consider When Choosing Therapies

Ryan Haumschild PharmD, MS, MBA, is director of Pharmacy Services at Emory Healthcare and Winship Cancer Institute, where he has wide range of clinical and management responsibilities for one of the nation’s largest academic integrated delivery networks. Winship is Georgia’s only NCI-Designated Comprehensive Cancer Center. Haumschild is a member of the editorial board for 

®) and a board member for the Center for Biosimilars®. He spoke with 

® about health care resource utilization and clinical decision support in the care of patients with small cell lung cancer (SCLC).

This interview is lightly edited for clarity.

®:Let’s start by discussing health care resource utilization. What does it look like for a patient who is newly diagnosed with small cell lung cancer (SCLC), or one who is progressing into the treatment stage? Which areas of the health care system does the patient touch on a day-to-day basis?

 Before a patient begins lung cancer treatment, they're going to review the pathology with a lung pathologist. This is critical, because small cell lung cancer responds well to chemotherapy, but it is not always treated surgically. We want to make sure it's not confused with non-small cell lung cancer, because the diseases involve 2 different, distinctive treatment strategies.

We'll also look at the immunohistory and examine the techniques for diagnosis and subclassification. Then, we're going to determine: does this patient have more limited disease, or extensive disease? And we talk about that because there are different therapy approaches based on whether the patient’s disease is limited or extensive. We know that patients with limited disease usually have immediate survival around 24 months and have higher 5-year survival rates around 14%. So, patients that have stage 1 or stage 2 newly diagnosed [SCLC] may be treated with surgery even though it's minimal, but often radiation therapy is something that's included as part of their treatment and health care utilization. Radiation therapy allows us to eradicate disease as much as possible. For those patients that don't wish to pursue surgery, radiation is another opportunity for us to reduce the size of the tumor burden.

We also want to complement that with chemotherapy. Typically, it's going to involve a platinum-based therapy or an etoposide. And currently, we're seeing base 3 drug regimens, such as utilizing 2 chemotherapies—we could use cisplatin or etoposide—combined with immunotherapy, such as atezolizumab or durvalumab. Those are typically the resources we see from an absolute treatment standpoint. We also see scans, and many of these patients who develop neutropenia, or any type of neuropathy will frequently visit the [emergency department]. And unfortunately, their 5-year survival isn't that strong yet, as we're still developing more medications. They will interact more often with an inpatient admission as part of their treatment regimen.

you evaluate the value of these treatments in SCLC, particularly when considering some of these new combinations? How do you evaluate the value of combinations with immune checkpoint inhibitors—atezolizumab or durvalumab—in the frontline setting? And then, there's also some newer agents in the second line, such as lurbinectedin. What is considered high value for these treatments?

 Right now, high value is anything that's going to improve overall survival. Among current treatments for extensive-stage small cell lung cancer, we have carboplatin and etoposide plus a checkpoint inhibitor. And that's where we're seeing the triplet approach to therapy right now, with atezolizumab or durvalumab as the checkpoint inhibitors. There are a few studies out there that show some improved data. The IMpower study had patients with some of the similar characteristics that we've discussed with metastatic small cell lung cancer.1 And they were randomized either to carboplatin-etoposide, with or without atezolizumab, and what we saw there was that patients that have evidence of response after about 4 cycles were offered atezolizumab and maintenance therapy. What it confirmed it is that both the progression-free survival and the overall survival are superior in the patient population that received atezolizumab in conjunction with carboplatin and etoposide.

That’s really where we start to see that benefit to patients, both clinically and in terms of extending out any type of progression-free survival. When we talk about durvalumab, that’s another great option. Which brings us to studies such as the CASPIAN trial,2 that also utilized and reviewed patients with metastatic small cell lung cancer. That trial had 3 arms, but what investigators looked at most closely was the combination therapy of carboplatin-etoposide or nutritional chemotherapy with durvalumab, compared with patients without. And again, [investigators] found when patients had chemotherapy with durvalumab, it improved their overall survival, which I think is the cornerstone of what we're trying to do for those patients. So, that's really where we're starting to see the value—the addition of the checkpoint inhibitor.

You also mentioned second-line therapy. What do we do when someone relapses? For a while, topotecan was really the only evidence-based standard of care in second-line therapy. You could have used something like cyclophosphamide, doxorubicin and vincristine, or a platinum rechallenge. But that's really such an antiquated [approach,] and there were not really strong survival data. So, we’ve had a new therapy approved, lurbinectedin.3 It was granted orphan-drug status and it provided an objective response rate of around 35% which is really, really strong. And we saw that initially in a phase 2 trial and then that became confirmed in a phase 3 trial. And so lurbinectedin, to me, represents a potential new treatment for these patients with small cell lung cancer—but that’s especially true those with few options that have basically relapsed in treatment, or they've been exposed to chemotherapy in the front line setting and have failed or progressed.

We've seen some studies with [lurbinectedin] being utilized as a single agent; also, there are studies with a combination with doxorubicin or paclitaxel. But as a single agent, it's demonstrated a pretty strong clinical efficacy with that 35% overall response rate, and it improved the median duration of response at around 5 months, which is significantly better than topotecan, which was historically the second-line treatment.

®:When we talk about these therapies, what clinical and nonclinical considerations do you find to be of high value in small cell lung cancer? For example, what is a clinically significant increase in survival that you'd love to see in a new agent, or a safety profile that you'd like to see if something new came to market and the sponsors really hoped to make a splash in small cell lung cancer?

 The good thing about small cell lung cancer is that there's opportunity for improvement in all those areas—and I think we're always trying to improve that journey for our patients.

We ask, what are the clinical and nonclinical outcomes? Let’s start with clinical: we leverage some of our real-world evidence or some of this additional data coming out of randomized controlled trials, so that we can improve overall survival. I think that's where the biggest opportunity exists. Also important is progression-free survival. We have several different therapies where we look at medium duration of response. How quickly can we see that duration of response to therapy? But to me, I guess the main thing that I think about a lot is the 5-year survival rate, it's still really low for small cell lung cancer patients. As we go through the journey and talk to patients, that's something they recognize can sometimes be less motivating because they know that even going through chemotherapy, even with this innovation of PD-L1 or these new cytotoxic agents, we still have opportunity for improvement.

I think those clinical outcomes are going to drive therapy, but while we're getting there and the way we keep patients on therapy I think is managing the side effect profile. When we look at some of these patients, you want to reduce the amount of abandonment rates. So even though we may not have high 5-year survival rates, how do we reduce abandonment rates—and that's really focusing on the treatment toxicities. When we look at some of these medications, even with the immunotherapies, we think of ototoxicity and neuropathy that are frequently seen with patients, that will cause them to abandon therapy. Or when we think about newer agents in the second-line setting like lurbinectedin, you also want to decrease the amount of neutropenia. So, I think early on, supportive care therapy is going to be important. Improving patient-reported outcomes—because we know those are tied heavily to adherence—and their motivation [to stay on] therapy will create a huge improvement.

The last item, and one of the most important ones, is reducing the amount of financial toxicity. It’s great that we're adding more therapies but if we think about traditionally in small cell lung cancer, there was an immunotherapy. So now as we have triple therapies, patients must come on-site, which requires transportation, it requires monitoring, it requires premedications, and potentially growth factors that are being proposed to them. How do we make sure patients can afford these types of therapies? And I think more we can leverage patient assistance programs, utilizing medication assistance but not just for medication but also coordination and supportive care. I think that's what ultimately is going to support patients and then eventually reduce total cost of care. Because if patients are staying adherent, we're minimizing these side effects. That means fewer emergency department visits and, hopefully, fewer admissions on the inpatient side of care.

®:Many institutions are using clinical pathways or clinical decision support tools to assist in driving patients and physician towards high-value treatments. When it comes to that shared decision-making process, is your institution using these tools, and if so, can you discuss the support structure in place for small cell lung cancer?

 I'm thankful that our institution has embraced shared decision-making. As a matter of fact, it's actually a core value of our organization. I think it’s especially important in small cell lung cancer to make sure that everyone is using the most efficacious treatment. We want to drive the most appropriate utilization in the frontline setting, and one of the ways you do that is complemented with pathways—and pathways that are reinforced through order sets to provide a high standard of care across all our sites, whether you're a subspecialist or you're a community oncologist. The way to work together is to develop disease state working groups where you have shared decision-making between your community oncologist and your aerodigestive or lung subspecialist. That way you can have agreement on what's the best way to treat small cell lung cancer patients. We need to make sure that people are leveraging that triplet therapy with the PD-L1 inhibitor in that frontline treatment setting—and that they are knowing exactly how to pivot to second line to give their patients the best overall survival and progression-free survival. So, within these pathways, it can take away that variability, which allows us to build in some of that side effect management that we know is so important to reduce abandonment rates.

Ultimately, it allows us to continue to monitor our real-world evidence as more therapies come forward. We can include these data in pathways, and we can make updates those pathways as we get more institution-specific data to make sure that we're keeping in mind diverse populations. I think the last thing about pathways is that you can leverage real-world evidence to address health equity and reach underserved patients. You can make sure that you have pathways that fit not just the entire patient population but are considered [responsive] to the most underserved populations. So, that's what we do. It allows us to be effective, and it allows that patient to receive that same high level of care, whether they go to a subspecialist or community oncologist that's close to their home.

®: I'd like to dive a little bit deeper into the topic of shared decision-making. How are pharmacists and physicians and perhaps other practitioners at your institution collaborating and having the shared decision-making approach with patients? What is their role in driving high-quality outcomes in small cell lung cancer?

 You've got to include multiple people of the care team, and I think that multidisciplinary approach allows patients to be most successful. How do we incorporate pharmacists? Well, pharmacists sit elbow to elbow with that physician provider as well as that advanced practitioner, as well as the clinic nurse—so they're seeing that patient in person. I think that's so valuable. But in addition, they’re also doing work on the back end, so they're developing order sets, they're developing monographs for these medications, and they're making sure that we're including the latest information, whether it be from [National Comprehensive Cancer Network] guidelines, from abstracts, or from research that we're doing internally here. With all that, you must build in not only great treatment pathways, but you must build in education for the patient. The reason I say that is if the patient expects one thing and you're not educating them on that subsequent therapy, ultimately, they could be confused. They may not feel good about dose reductions, and they may want to stop altogether.

So, our pharmacists actually sit in clinic. They work up patients next to their physicians and then they give recommendations on the treatments once those scans and a definitive diagnosis comes back from pathology. But in addition to that, we build out patient-specific education so the patient knows what their journey may be like. We educate them on why we're doing chemotherapy. Maybe we discuss why we're adding on a checkpoint inhibitor, and why immunotherapies are now providing additional benefit to the patient—and what side effects to anticipate. And we educate them on the supportive care medications we're providing them so that if there's any weight-limiting toxicities, they can report those to us. But they also have the medications on hand to take them to reduce any type of toxicity progression and ultimately, we talked on the importance about adherence. Stay adherent to your therapy but if you're having side effects when you do any type of dose reductions, let us know. That might be a normal part of your patient care journey. It doesn't mean that you're going to have less efficacious treatment. It just means you're going to be able to stay on treatment longer. And so, our pharmacists provide this education and lastly monitor these patients and do check-ins based on their different cycles to make sure that we're titrating their doses appropriately. And if there's any financial toxicity, we're engaging the right members of our patient assistance team to get them engaged and reporting that out through the electronic medical record and the provider.

®: Are there any other thoughts on the topic of small cell lung cancer that you’d like to share with your colleagues or our audience here at 

 Treatment of small cell lung cancer is changing, and we've got to make sure we’re on board and adopting those newer, innovative therapies earlier. But we also must recognize that with small cell lung cancer, not everyone's an expert. So, how do we leverage some of these pathways, or some of these order sets or standard approaches, into care so that we offer practitioners who see multiple solid tumor disease states the information they need to start patients on the right therapy early on? How do we incorporate education?

Patients are on the same page, and they have shared expectations around treatment. I think that's obviously extremely important. Again, how do we look forward to seeing the research breaking on some of these immunotherapies, so that we can leverage this information when these therapies are ready to be added to formulary? And then lastly, how do we leverage efficacy data from different cooperative group trials, such as atezolizumab and chemoradiation or durvalumab and some of these newer therapies, to provide better overall survival and reduce a lack of response in the second line or later?

And then lastly, I think we've got to be cost-conscious about these therapies. We've got to recognize that we can maybe take on some of these therapies on the front end. We worry about that patient’s out-of-pocket costs, but we might be able to decrease total cost of care if we get patients on the right therapy sooner. And then at the end of the day, we must recognize that there's high mortality for 5-year mortality, and 5-year survival rates are rather low right now, so we need to continue to enroll patients in clinical trials as appropriate to add to the body of data to provide more therapies for these patients.

Horn L, Hansfield AS, Szczesna A, for the IMpower 133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small cell lung cancer. 

 2018;379:2220-2229. DOI: 10.1056/NEJMoa1809064

Goldman JW, Dvorkin M, Chen Y, et al., for the CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum etoposide alone in first-line treatment of extensive-stage small cell lung cancer (CASPIAN); updated results from a randomized, controlled, open-label phase 3 trial. 

. 2021;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8

FDA grants accelerated approval for lurbinectedin for metastatic small cell lung cancer. News release. FDA. June 16, 2020. Accessed May 18, 2022. 

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer

Ryan Haumschild PharmD, MS, MBA, director of Pharmacy Services at Emory Healthcare and Winship Cancer Institute, spoke with AJMC® about health care resource utilization and clinical decision support in the care of patients with small cell lung cancer (SCLC).

Emory’s Haumschild on Need for Clinical Pathways in SCLC: “Not Everyone’s an Expert”

US Senate Releases FDA Safety and Landmark Advancements Act Draft

Senators Richard Burr, R-North Carolina, and Patty Murray, D-Washington, of the Senate Health, Education, Labor and Pensions (HELP) Committee released a draft of the FDA Safety and Landmark Advancements (FDASLA) Act yesterday. As reported in a 

, the FDASLA Act would reauthorize the FDA’s user fee agreements for biosimilars, medical devices, and prescription and generic drugs. The legislation would also strengthen the FDA’s role in overseeing dietary supplements and cosmetics, improving diagnostic test regulation—including COVID-19 tests—and increasing competition to reduce drug prices, among other areas. The FDASLA Act will also ensure transparency and accountability from the FDA regarding user fees it collects from industry.

A monkeypox outbreak in the United Kingdom has raised concerns from the CDC, which worries there may be additional undetected transmission of the virus and that it could spread into other nations. 

 reported 7 confirmed cases and 1 probable case of monkeypox since early May, which is deemed a large number considering monkeypox is generally uncommon and especially rare outside of West and Central Africa. One person with the virus had recently traveled to Nigeria, where monkeypox is endemic. While the rest of the cases appear to have been contracted within the United Kingdom, none of these people had any known connection to the person traveling from Nigeria and it appears that the individual was not the source of the domestic infections. However, among the 6 other cases and the probable case, 3 of them are a family unit and 4 are men who have sex with men, making 2 distinct groups with no connection to each other. Investigation into the outbreak is ongoing.

Report Shows Benefits, Financial Setbacks of Lowering Medicare Eligibility Age

 by the Congressional Budget Office and Joint Committee on Taxation on the effects of lowering the Medicare eligibility age from 65 to 60, the 2 groups found that although millions of more people would be insured, federal budget deficits would increase by $155 billion in the 2026-2031 period. According to the report, these deficits would be a result of federal revenue and mandatory spending policies, including having the federal government pay for health care instead of employers. The $155 billion increase reflects a total $222 billion increase in mandatory spending, slightly offset by a $67 billion increase in revenue.

New FDA legislation will reauthorize FDA user fee agreements for biosimilars, medical devices, and prescription and generic drugs; 7 cases of monkeypox have been confirmed in the United Kingdom, but its mode of transmission is still under investigation; according to a budget report, lowering the Medicare eligibility age to 60 would increase federal costs by $155 billion in a 5-year period.

What We’re Reading: FDA Legislation Draft; UK Monkeypox Outbreak; Effects of Lowering Medicare Eligibility Age

Christina is the assistant managing editor of 

 since 2016 and has a BS in public health and psychology from Rutgers University.

Investigators in the field of digestive disease and members of societies including the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American Society for Gastrointestinal Endoscopy, convene each year during 

 (DDW) to present the latest findings in digestive disease. 

This year, with the meeting welcoming in-person attendance for the first time since the COVID-19 pandemic hit, topics discussed and debated at DDW from May 21 to 24 will include the gut/brain/microbiome axis, the possibility of preventing or reversing disease, the importance of whole-person treatment, and more.

The Complex Impact of the Microbiome on Health

Recent years have seen increasing awareness of and research on the gut microbiome, or the community of microorganisms found in the digestive system, and its impact on disease states ranging from 

. DDW 2022 will feature a number of sessions and abstracts on the microbiome, including a symposium on gut microbiota as a biomarker of digestive health and overall nutrition, as well as a lecture on the potential harms of pursuing optimal gut health.

Restoring the microbiome can be an objective of treatment for 

, and abstracts will discuss the promising results of new therapies in accomplishing this goal. Additionally, investigators previewing their findings in a press call ahead of the meeting noted that the microbiome is implicated in the discovery that antibiotic treatment 

 for development of inflammatory bowel disease (IBD) in older patients.

Recovery of Patients and Physicians After COVID-19

COVID-19 and its ramifications are inescapable as a topic of discussion at every major medical meeting, and DDW 2022 will be no exception. As the United States shifts its approach to the pandemic, more research is focusing on the long-term effects of both the disease itself and its disruption of normal life. A State-of-the-Art Lecture at DDW will explore how alcohol use disorder may have impacted liver health in the United States over the past 2 years and how hepatologists can help their patients recover post pandemic.

Physician practices may also need to recover from the financial challenges posed by the pandemic, so lectures will aim to advise clinicians on how to recover their work-life balance, navigate the new normal of telehealth, and successfully encourage patients to return to the physician’s office.

Moving Upstream From Treatment to Reversal and Prevention

DDW 2022 will feature a plethora of abstracts and lectures on new methods of treating disease, but the program also reveals an emphasis on reversing established disease or even preventing it from occurring at all. Speakers at a symposium will discuss how diet and lifestyle changes, microbiome health, and drugs such as aspirin may be harnessed to prevent the development of gastrointestinal cancers.

The potential of prevention is not limited to cancer, as other sessions will cover prevention of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. Even if disease cannot be prevented, researchers are aiming to reverse its effects, as will be discussed in a lecture on how weight loss therapies may help to reverse the trajectory of NAFLD.

Whole-Person Treatment of Digestive Disease

Several sessions at DDW 2022 will focus on holistically understanding the patient at the center of digestive disease in order to best predict risk and support the patient’s needs. For instance, a lecture about the “food environment” aims to explore how a person’s genes, gastrointestinal phenotype, environment, and diet all collide to contribute to their risk of obesity. There will also be a symposium discussing how health disparities—including structural violence, racial inequities, and discrimination—influence the human microbiome and colorectal cancer risk.

Keeping the whole patient in mind is key to successful treatment, not just identifying elevated risk. A lecture will educate attendees on the serious psychological impacts of living with IBD, which can include sleep disturbances, anxiety, and even posttraumatic stress disorder, and how patients can learn to manage these impacts through the help of therapy.

Harnessing AI and Tech for Treatment and Practice Management

Numerous abstracts will present findings on the use and outcomes of telehealth among patients with digestive diseases, including adherence to pre-endoscopy consultations performed virtually vs in person and patient satisfaction with video visits for conditions such as gastroesophageal reflux disease and IBD.

In addition to the discussions of telehealth as a continuing presence beyond the COVID-19 pandemic, other sessions will address how digital technologies and artificial intelligence (AI) can help practitioners and patients. A symposium will feature presentations on the use of AI in colonoscopy, upstream patient identification, medical record maintenance, and more. Another lecture will focus on the use of robotic technologies in endoscopy and the potential of AI to assess IBD severity.

Digestive Disease Week (DDW) 2022, held virtually and in San Diego, California, from May 21 to 24, will feature research and presentations exploring new ways to prevent and treat digestive diseases.

Importance of Microbiome, Disease Prevention Among Topics to Be Discussed at DDW 2022

Laura is the vice president of content for The American Journal of Managed Care

) and all its brands, including The American Journal of Accountable Care

, Evidence-Based Oncology™, and The Center for Biosimilars

, since 2011. She also oversees Managed Healthcare Executive

She has an MA in business and economic reporting from New York University. You can reach her at 

 is a safe bet as the top spend category for the next few years, said Sneha Sharma, PharmD, director, specialty clinical solutions, Magellan Rx, said in Las Vegas during the Asembia Specialty Pharmacy Summit, held May 2-5.

During her presentation, Sharma ran through the trends in the commercial, Medicare, and Medicaid populations, and oncology was the top spend category in all 3. Starting with commercial, she noted that oncology trends approximately 15% higher in per-member per-month (PMPM) spend than other categories.

“This keeps in line with the trend that oncology is becoming its own entity,” Sharma said.

The top 5 categories of spend in commercial were oncology, biologic drugs for autoimmune disorders (BDAIDs; eg, Crohn disease, ulcerative colitis), multiple sclerosis, ophthalmic injections, and asthma/chronic obstructive pulmonary disease.

Overall, the top 5 categories made up 70% of the medical benefit PMPM, with oncology making up 46% on its own.

In the Medicare population, oncology is again the top spend and utilization category, and the PMPM between oncology and all other therapies differs by as much as 35%. The COVID-19 lockdowns and stay-at-home orders had a bigger impact on oncology claims in this population compared with the commercial population, Sharma noted.

The top 5 categories of spend in Medicare were oncology, followed by ophthalmic injections, hematology, bone resorption inhibitors, and BDAIDs. These 5 categories made up 80% of the medical benefit PMPM, with oncology making up 59% alone.

Finally, looking at the Medicaid space, Sharma noted the varying patient trends and needs. “With the influx of unemployment and economic upheaval that we saw due to COVID, Medicaid saw some large increases in their medical benefit PMPM spend at about a 7% increase in PMPM,” she said.

There was a little variation in the top 5 categories of spend, although oncology was still at the top. The other 4 were BDAIDs, rare diseases, multiple sclerosis, and immune globulin. These top 5 categories made up 62% of the medical benefit PMPM, and oncology made up 37% alone.

Sharma noted that while there were variabilities across lines of business, oncology was the exception. However, oncology utilization was down 4.8% in commercial, 9.3% in Medicare, and 13.8% in Medicaid compared with prepandemic levels in 2019.

Looking ahead at the drug pipeline, Sharma focused on gene therapies and oncology drugs because these categories will continue to drive spend. “Payers are most concerned with the trend in oncology and impact of gene therapy,” she said. “These 2 high-cost, high-impact categories have robust pipelines and unique management requirements.”

Among the drugs she highlighted in the pipeline were:

 to treat transfusion-dependent beta-thalassemia and sickle cell disease. This intravenous (IV) drug has a Prescription Drug User Fee Act (PDUFA) date of August 19, 2022, and the cost could be $1.8 million.

 to treat hemophilia B. While there are hemophilia drugs on the market, this is a gene therapy, and it treats a rarer form of hemophilia. The drug is also delivered intravenously. The pivotal trial concludes May 2022, with results expected in the first quarter of 2023.

 to treat HER2-positive breast cancer, metastatic gastric cancer, or gastroesophageal junction adenocarcinoma. This IV administered drug has an expected approval timeline of the third quarter 2022. There has been a new trastuzumab biosimilar approval every 1 to 2 years, Sharma said, and “it's very exciting to have more choices.”

 to treat relapsed or refractory multiple myeloma. This off-the-shelf B-cell maturation antigen is delivered intravenously and is being evaluated as both a monotherapy and in combination therapy, and the preliminary results indicate it may have a substantial improvement on at least 1 end point over current therapy, Sharma said.

“Drugs within our gene therapy and oncology pipelines are becoming more specific, somewhat complicated, and fulfilling needs in patient populations where standard nonspecific therapies or no therapies have existed,” Sharma said. “We must continue to evaluate and manage these trends with programs that we know are working or continue to find informative strategies for high-cost specialty drugs.”

Across commercial insurance, Medicare, and Medicaid populations, oncology is the top category of spend, and the drug pipeline has increasing specific and complex therapies.