Blood & Cancer

A pair of biomarkers are being used to guide treatment and predict mortality in patients with graft-versus-host disease (GVHD), according to James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

In this episode, Dr. Ferrara explains how measuring these biomarkers – REG3-alpha and ST2 – can prevent over- and undertreatment of acute GVHD. The biomarkers have also been shown to predict nonrelapse mortality more accurately than a change in clinical symptoms.

Before reviewing these findings, Dr. Ferrara tells host David H. Henry, MD, what GVHD is, how to recognize it, and how it’s typically treated.

GVL and GVHD

• GVHD is “very tightly associated” with the graft-versus-leukemia (GVL) effect, Dr. Ferrara explained.
• The GVL effect refers to the ability of donor immune cells to eliminate host malignant cells after allogeneic hematopoietic stem cell transplant (allo-HSCT).
• The donor T cells respond to minor histocompatibility antigens on malignant cells but also on normal cells.
• When the donor T cells attack the normal cells, the patient develops GVHD.
• To prevent GVHD, patients may receive cyclosporin, tacrolimus, methotrexate, sirolimus, or other drugs in various combinations.
• Despite prophylaxis, slightly under half of allo-HSCT recipients will still develop some form of GVHD, Dr. Ferrara said.

Acute GVHD

• Acute GVHD typically occurs in the first month or two after transplant, and about 50% of cases happen in the first month, Dr. Ferrara said.
• There are three primary targets – the skin, liver, and GI tract.
• The rash observed with skin GVHD is vesiculopapular, and the extent of the rash determines the stage of GVHD in the skin.
• Increase in total bilirubin is used to measure the stages of liver disease.
• GVHD in the GI tract is characterized by persistent nausea and vomiting or diarrhea (up to liters a day).
• Evaluating the skin, liver, and GI tract together can provide the overall GVHD grade, between 1 and 4.
• Grade 4 GVHD is the most severe, and grade 1 is a skin rash that usually affects less than 50% of the body surface area.

Over- and undertreatment

• When GVHD is mild and limited to the skin, topical steroid creams are adequate treatment.
• When GVHD progresses into the GI tract and liver, patients require systemic immunosuppression.
• However, it’s difficult to tell whether GVHD is going to be mild, moderate, or severe.
• So when patients with acute GVHD receive systemic steroids at a starting dose of 1 mg/kg, many of these patients are overtreated “and a fair number of them are undertreated because we don't actually know which patients are going to progress and which patients are going to respond to treatment,” Dr. Ferrara said.
• He noted that the JAK1/2 inhibitor ruxolitinib was approved to treat steroid-refractory acute GVHD last year. Prior to that, the only approved treatment for GVHD was systemic steroids.

Biomarkers signal disease severity

• Through their research, Dr. Ferrara and colleagues identified two biomarkers of GVHD severity – REG3-alpha and ST2.
• “When the GI tract is damaged early, these proteins flood into the systemic circulation, and they can actually tell us who's got a damaged GI tract very early, even before one has symptoms like diarrhea,” Dr. Ferrara explained.
• The biomarkers can be used to assess, at the onset of GVHD, whether or not a patient has crypt damage and needs more intensive treatment.

Biomarkers guide treatment, predict outcomes

• Dr. Ferrara and colleagues used serum samples collected by the Mount Sinai Acute GVHD International Consortium (MAGIC) to develop MAGIC Algorithm Probability (MAP).
• MAP is calculated from patients’ levels of REG3-alpha and ST2 and can be used to predict the risk of severe GVHD.
• “You put these two biomarkers into an equation, you get a single number, and that number tells you whether [the patient is] high risk, low risk, or intermediate risk,” Dr. Ferrara explained.
• He and his colleagues found they could use MAP to predict patients’ response to treatment and mortality.
• In fact, MAP was able to predict nonrelapse mortality more accurately than a change in clinical symptoms (Blood Adv. 2019. 3[23]:4034-42. https://bit.ly/39QNUVn).

Standard practice, ongoing trials

• MAP is increasingly becoming a part of standard practice, Dr. Ferrara said.
• A company called Viracor Eurofins Clinical Diagnostics licensed MAP and provides tests for consumer use (https://bit.ly/33RhRBa).
• Centers can send blood samples to Viracor to test.
• More than 50 centers in the United States sent at least 1,000 samples to Viracor for testing in 2019, Dr. Ferrara said.
• He and his colleagues are also utilizing MAP in ongoing clinical trials:
  • A phase 2 study of natalizumab plus standard steroid treatment for high-risk acute GVHD (NCT02133924; https://bit.ly/3grvsUK).
  • A pilot trial of alpha1-antitrypsin for preemption of steroid-refractory acute GVHD (NCT03459040; https://bit.ly/3qy48c9).
  • A phase 2 trial of itacitinib for low-risk GVHD (NCT03846479; https://bit.ly/37GkaYK).

Disclosures:

Dr. Ferrara has a patent for serum biomarkers of acute GVHD and receives royalties from Viracor. Dr. Henry has no relevant disclosures.

*  *  *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Blood & Cancer news stories:

1. Black patients with ES-SCLC get less chemo but have better survival: https://bit.ly/33Rb5eB
   
   
2. Should CTCs guide treatment choice in HR+, HER2– breast cancer?: https://bit.ly/3gn6shc
   
   
3. New drug approved for relapsed/refractory neuroblastoma: https://bit.ly/2VMpvIy
   
   
4. FDA approves first agent for PSMA-PET imaging in prostate cancer: https://bit.ly/36TAaY7

Contact Blood & Cancer at [email protected].

Researchers are conducting the first U.S. trial of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for the treatment of peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers.

Coprincipal investigator Thanh H. Dellinger, MD, of City of Hope in Duarte, Calif., describes this trial and the PIPAC procedure to host David H. Henry, MD, in this episode.

To start, the pair discuss a patient who might be eligible for PIPAC – one with stage 3 ovarian cancer.

General approach to stage 3 ovarian cancer

• Therapy typically includes a combination of surgery and chemotherapy.
• The order in which chemotherapy is given, either pre- or postoperatively, depends on performance status and whether patients have extra-abdominal disease or parenchymal liver disease.
• Operative approaches, including debulking surgery, are pursued if believed to be optimal, meaning all gross residual disease can be resected.
• If all residual disease cannot be resected, patients are offered neoadjuvant chemotherapy, typically for three to four cycles before an interval debulking surgery, followed by postoperative adjuvant chemotherapy.

Intraperitoneal chemotherapy

• Intraperitoneal (IP) chemotherapy is used to treat peritoneal surface malignancies.
• The peritoneum is a separate organ that is difficult to treat adequately with intravenous chemotherapy alone.
• Giving IP chemotherapy in combination with intravenous chemotherapy may be more effective than intravenous chemotherapy alone (N Engl J Med. 2006; 354:34-43; https://bit.ly/3g3lngx).
• However, there are many challenges in delivering IP chemotherapy, including increased side effects of abdominal pain and IP catheter failure.
• Recent clinical trials have shown that, with the addition of bevacizumab, the survival benefit with IP chemotherapy may not be as significant as prior trials suggested (J Clin Oncol. 2019 Jun 1;37[16]:1380-90; https://bit.ly/2VAmRVW).
• In general, IP chemotherapy has not been embraced by the medical oncology community as much other types of chemotherapies, Dr. Dellinger said.

What is PIPAC?

• PIPAC is a novel therapy discovered by a German surgical oncologist, Marc A. Reymond, MD, from University of Tuebingen (Germany).
• PIPAC delivers chemotherapy at a reduced dose directly into the intraperitoneal cavity but in a pressurized and aerosolized form.
• PIPAC is done at the time of the diagnostic laparoscopy and requires a nebulizer for aerosolization of the chemotherapy as well as a high-pressure injector.
• This approach allows for the chemotherapy to be pushed deeper into tissues, compared with hyperthermic intraoperative peritoneal chemotherapy (HIPEC).
• With HIPAC, tissue penetration is typically 1 mm or less. With PIPAC, there is deeper penetration and better distribution of chemotherapy throughout the entire intraperitoneal cavity.
• With PIPAC, chemotherapeutic agents are given at a lower dose than is typically administered with IP or intravenous chemotherapy, which helps in reducing the toxicity.
• PIPAC is given every 6 weeks for three cycles, requiring three laparoscopic procedures.
• These laparoscopic procedures allow for the opportunity to obtain peritoneal tumor biopsies before and after to investigate the natural course of these tumors and their microenvironment.

Toxicity of PIPAC

• PIPAC has been done in more than 800 patients with gastrointestinal and gynecologic cancers in Europe and Asia.
• Severe adverse events  have been minimal, with about 12%-15% grade 3/4 SAEs and very rare grade 5 SAEs.
• The most common side effect is typically abdominal pain, attributed to the IP administration in conjunction with the laparoscopic surgery.
• Renal toxicity is a concern with intravenous cisplatin use, but this has not yet been seen with PIPAC.
• With PIPAC, cisplatin is given at 10.1 mg/m² and doxorubicin is given at 2.1 mg/m², doses that are much lower than the typical doses for these drugs.

PIPAC in clinical trials

• PIPAC clinical trials have moved into phase 2 in Europe for ovarian cancer, with a publication demonstrating an objective response rate of over 60% in platinum-resistant ovarian cancer (Gynecol Oncol. 2015 May;137[2]:223-8; https://bit.ly/2KY701r).
• A phase 3 trial of PIPAC was planned but was stalled because of the COVID-19 pandemic.
• Because of the need for Food and Drug Administration approval, researchers have just launched the first phase 1 trial of PIPAC in the United States.

Phase 1 trial of PIPAC

• City of Hope is working with affiliates at Mayo Clinic in Jacksonville, Fla.; Northwell Health in New York; and the National Institutes of Health to enroll eligible candidates for a phase 1 trial (NCT04329494; https://bit.ly/3qs8H7U).
• Eligible candidates include those with gastric, uterine, colorectal, appendiceal, and ovarian cancer with evidence of peritoneal carcinomatosis who have failed at least one line of therapy.
• PIPAC is an outpatient procedure, but given the trial and need for monitoring, patients typically leave the hospital the following day after blood samples are obtained for the study.
• City of Hope has recruited seven patients since activating their study in August 2020, with a goal of enrolling 16 patients by spring 2021.

Future directions

• Peritoneal tumor biopsies obtained during the laparoscopic procedures are being used to study the microenvironment of these cancers.
• In eventual phase 2 clinical trials, the researchers may include immune checkpoint inhibitors.
• Biomarker analyses are underway, looking at expression of PD-1 and tumor-infiltrating lymphocytes.
• The researchers are also studying the role of genomic sequencing and DNA repair.

Disclosures:

Dr. Dellinger and Dr. Henry have no financial disclosures relevant to this episode.

Show notes by Sheila De Young, DO, resident at Pennsylvania Hospital, Philadelphia.

*  *  *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Researchers are conducting the first U.S. trial of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for the treatment of peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers.

Coprincipal investigator Thanh H. Dellinger, MD, of City of Hope in Duarte, Calif., describes this trial and the PIPAC procedure to host David H. Henry, MD, in this episode.

To start, the pair discuss a patient who might be eligible for PIPAC – one with stage 3 ovarian cancer.

General approach to stage 3 ovarian cancer

• Therapy typically includes a combination of surgery and chemotherapy.
• The order in which chemotherapy is given, either pre- or postoperatively, depends on performance status and whether patients have extra-abdominal disease or parenchymal liver disease.
• Operative approaches, including debulking surgery, are pursued if believed to be optimal, meaning all gross residual disease can be resected.
• If all residual disease cannot be resected, patients are offered neoadjuvant chemotherapy, typically for three to four cycles before an interval debulking surgery, followed by postoperative adjuvant chemotherapy.

Intraperitoneal chemotherapy

• Intraperitoneal (IP) chemotherapy is used to treat peritoneal surface malignancies.
• The peritoneum is a separate organ that is difficult to treat adequately with intravenous chemotherapy alone.
• Giving IP chemotherapy in combination with intravenous chemotherapy may be more effective than intravenous chemotherapy alone (N Engl J Med. 2006; 354:34-43; https://bit.ly/3g3lngx).
• However, there are many challenges in delivering IP chemotherapy, including increased side effects of abdominal pain and IP catheter failure.
• Recent clinical trials have shown that, with the addition of bevacizumab, the survival benefit with IP chemotherapy may not be as significant as prior trials suggested (J Clin Oncol. 2019 Jun 1;37[16]:1380-90; https://bit.ly/2VAmRVW).
• In general, IP chemotherapy has not been embraced by the medical oncology community as much other types of chemotherapies, Dr. Dellinger said.

What is PIPAC?

• PIPAC is a novel therapy discovered by a German surgical oncologist, Marc A. Reymond, MD, from University of Tuebingen (Germany).
• PIPAC delivers chemotherapy at a reduced dose directly into the intraperitoneal cavity but in a pressurized and aerosolized form.
• PIPAC is done at the time of the diagnostic laparoscopy and requires a nebulizer for aerosolization of the chemotherapy as well as a high-pressure injector.
• This approach allows for the chemotherapy to be pushed deeper into tissues, compared with hyperthermic intraoperative peritoneal chemotherapy (HIPEC).
• With HIPAC, tissue penetration is typically 1 mm or less. With PIPAC, there is deeper penetration and better distribution of chemotherapy throughout the entire intraperitoneal cavity.
• With PIPAC, chemotherapeutic agents are given at a lower dose than is typically administered with IP or intravenous chemotherapy, which helps in reducing the toxicity.
• PIPAC is given every 6 weeks for three cycles, requiring three laparoscopic procedures.
• These laparoscopic procedures allow for the opportunity to obtain peritoneal tumor biopsies before and after to investigate the natural course of these tumors and their microenvironment.

Toxicity of PIPAC

• PIPAC has been done in more than 800 patients with gastrointestinal and gynecologic cancers in Europe and Asia.
• Severe adverse events  have been minimal, with about 12%-15% grade 3/4 SAEs and very rare grade 5 SAEs.
• The most common side effect is typically abdominal pain, attributed to the IP administration in conjunction with the laparoscopic surgery.
• Renal toxicity is a concern with intravenous cisplatin use, but this has not yet been seen with PIPAC.
• With PIPAC, cisplatin is given at 10.1 mg/m² and doxorubicin is given at 2.1 mg/m², doses that are much lower than the typical doses for these drugs.

PIPAC in clinical trials

• PIPAC clinical trials have moved into phase 2 in Europe for ovarian cancer, with a publication demonstrating an objective response rate of over 60% in platinum-resistant ovarian cancer (Gynecol Oncol. 2015 May;137[2]:223-8; https://bit.ly/2KY701r).
• A phase 3 trial of PIPAC was planned but was stalled because of the COVID-19 pandemic.
• Because of the need for Food and Drug Administration approval, researchers have just launched the first phase 1 trial of PIPAC in the United States.

Phase 1 trial of PIPAC

• City of Hope is working with affiliates at Mayo Clinic in Jacksonville, Fla.; Northwell Health in New York; and the National Institutes of Health to enroll eligible candidates for a phase 1 trial (NCT04329494; https://bit.ly/3qs8H7U).
• Eligible candidates include those with gastric, uterine, colorectal, appendiceal, and ovarian cancer with evidence of peritoneal carcinomatosis who have failed at least one line of therapy.
• PIPAC is an outpatient procedure, but given the trial and need for monitoring, patients typically leave the hospital the following day after blood samples are obtained for the study.
• City of Hope has recruited seven patients since activating their study in August 2020, with a goal of enrolling 16 patients by spring 2021.

Future directions

• Peritoneal tumor biopsies obtained during the laparoscopic procedures are being used to study the microenvironment of these cancers.
• In eventual phase 2 clinical trials, the researchers may include immune checkpoint inhibitors.
• Biomarker analyses are underway, looking at expression of PD-1 and tumor-infiltrating lymphocytes.
• The researchers are also studying the role of genomic sequencing and DNA repair.

Disclosures:

Dr. Dellinger and Dr. Henry have no financial disclosures relevant to this episode.

Show notes by Sheila De Young, DO, resident at Pennsylvania Hospital, Philadelphia.

*  *  *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Blood & Cancer News Stories: 

1. Immune checkpoint inhibitors don’t increase COVID-19 incidence or mortality, studies suggest: https://bit.ly/2JlP2FN
2. HCC rates slow in cities, continue to climb in rural areas: https://bit.ly/2Jx6Ux1
3. Risk factors for severe immune-related AEs identified: https://bit.ly/3fO6Fd8

Contact Blood & Cancer at [email protected]

In this episode, host David H. Henry, MD, highlights some recent articles from Blood, the Journal of Clinical Oncology, and the New England Journal of Medicine.

Blood

• How I Treat series on hematologic complications in pregnancy. https://bit.ly/3fr5nV8
• Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. https://bit.ly/3nQvhF6

Journal of Clinical Oncology

• Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. https://bit.ly/3maTOE4
  
  • Related Blood & Cancer episode:
    Cancer and hepatitis B virus: ASCO's recommendations for HBV screening, monitoring for reactivation, and how to treat patients. https://bit.ly/3m0jjrF
• Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy. https://bit.ly/372FFCB
• Chemotherapy and COVID-19 Outcomes in Patients With Cancer. https://bit.ly/35WRLOi
  
  • Related Blood & Cancer episodes:
    Studying cancer patients with COVID-19: NCCAPS and CCC19. https://bit.ly/3pYl2Au
    TERAVOLT registry sheds light on patients with thoracic cancers and COVID-19. https://bit.ly/2URdwJh
• Diffuse Large B-Cell Lymphoma’s New Genomics: The Bridge and the Chasm. https://bit.ly/36XdGnY

New England Journal of Medicine

• Osimertinib in Resected EGFR-Mutated Non–Small Cell Lung Cancer. https://bit.ly/2J5q7FQ
• Humoral Immune Response to SARS-CoV-2 in Iceland. https://bit.ly/2USw7ET
• Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. https://bit.ly/39aM0ia
• Remdesivir for the Treatment of COVID-19 – Final Report. https://bit.ly/375dYJk
• Remdesivir for 5 or 10 Days in Patients with Severe COVID-19. https://bit.ly/2IZJ7Wq

Disclosures:

Dr. Henry has no relevant disclosures.

*  *  *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

In this episode, we discuss updated guidelines on the screening and management of hepatitis B virus (HBV) in patients about to start anticancer therapy. The guidelines come from an American Society of Clinical Oncology Provisional Clinical Opinion (PCO) published earlier this year.

Jessica P. Hwang, MD, of MD Anderson Cancer Center, and Andrew Artz, MD, of City of Hope, are cochairs of the ASCO PCO. They joined host David H. Henry, MD, to discuss the guidelines.

Epidemiology of HBV

• Data suggest chronic HBV infection affects 257 million people globally.
• In the United States, chronic HBV infection has a prevalence of less than 1%, but the prevalence of past HBV can be 5%-40% in high-risk populations.
• High-risk populations include people born in endemic areas (i.e., Africa, Asia, and South America), those with injection drug use, men who have sex with men, and people with household contacts who have HBV.
• In patients with cancer, the prevalence of past HBV infection is 5%-10%, with a 0.5% prevalence of chronic HBV.

HBV and oncology: Who should be screened?

• The ASCO PCO recommends universal HBV screening in all patients planning or undergoing anticancer therapy.
• To screen, practitioners should order three tests before initiating anticancer therapy: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and hepatitis B surface antibody (anti-Hbs).

Interpretation of serology

• Chronic infection: HBsAg (+), anti-HBc (+), anti-HBs (-).
• Resolved past infection: HbsAg (-), anti-HBc (+), anti-HBs (+).
• Past infection, isolated core: HbsAg (-), anti-HBc (+), anti-HBs (-).
• Vaccine-induced immunity: HbsAg (-), anti-HBc (-), anti-HBs (+).

Recommended treatment and/or monitoring

• Once a patient is infected, the HBV incorporates into the host genome and can live latently, so the patient is at risk of reactivation with immunosuppressive anticancer therapy (with chronic or past infection).
• Certain therapies pose a heightened risk of HBV reactivation, including anti-CD20 monoclonal antibodies and stem cell transplant.
• Patients receiving checkpoint blockade immunotherapy should be monitored closely for reactivation, though autoimmune hepatitis and high-dose steroids used in treating immune-related events could confound the reactivation of HBV.
• Further guidelines specific to checkpoint blockade immunotherapy are dichotomized and can be found in the ASCO PCO.
• In patients with chronic HBV infection receiving any systemic anticancer therapy, the ASCO PCO recommends antiviral prophylactic therapy during anticancer therapy and for a minimum of 12 months after anticancer therapy, with consultation of an HBV specialist.
• Entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide are well tolerated and have a low rate of viral resistance, making them favorable for patients who need to be treated.

Implementing a screening program

• Recommend a multidisciplinary team approach, including physicians, pharmacists, and public health professionals.
• Utilize EHRs to incorporate alerts for screening and embedding screening into order sets.
• Ensure that positive test results are delivered to the appropriate medical team.
• Link patients into care for treatment and/or monitoring.

Source and resources

• The ASCO PCO was published in the Journal of Clinical Oncology: https://bit.ly/3pClNPo.
• Additional resources are available on the ASCO website: https://bit.ly/35E0nt0.
• An infographic is also available: https://bit.ly/3pBuE3K.

Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures

Dr. Hwang disclosed relationships with Gilead Sciences, Merck Sharp & Dohme, and the Asian Health Foundation. Dr. Artz disclosed research funding from Miltenyi Biotec. Dr. Henry has no relevant disclosures.

*  *  *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

The Tomosynthesis Mammography Imaging Screening Trial (TMIST) was designed to see if 3-D mammography, or tomosynthesis, could help personalize screening and if 3-D is actually better than the less expensive 2-D mammography.

TMIST is the largest breast cancer screening trial in the United States, with a cost of $100 million and a planned enrollment of 165,000 women.

There's just one problem. The study is falling short on enrollment of patients and participating sites. Will this mean the death of TMIST?

For more details, see coverage of TMIST on Medscape:
NCI May 'Kill' Major Mammography Trial, Says Advisor
https://www.medscape.com/viewarticle/937918

Email Blood & Cancer at [email protected].

Can receiving all posttransplant care at home benefit patients undergoing hematopoietic stem cell transplant (HSCT)? Researchers are conducting phase 2 trials to find out.

Anthony D. Sung, MD, of Duke University School of Medicine, described this research to host David H. Henry, MD.

Dr. Sung outlined the process of receiving post-HSCT care at home and discussed Duke's clinical trials assessing the impact of home care on costs, quality of life, the microbiome, and graft-versus-host disease (GVHD).

Dr. Sung also discussed another Duke trial investigating whether a probiotic can prevent COVID-19.

Post-HSCT care at home: How it works

• Cell collection (if applicable), conditioning, and HSCT all take place in the outpatient setting.
• From day 1 after transplant onward, the patient receives all care at home.
• A nurse practitioner or physician assistant visits the patient every morning to draw labs, which are run at the hospital.
• A nurse visits every afternoon to give the patient supportive care.
• Patients are given the tools to video chat with physicians.
• Patients must live within 1 hour of Duke’s transplant center or relocate to furnished apartments near the transplant center.

Phase 1 trial: Feasible and safe

• Dr. Sung and colleagues have completed a phase 1 trial, which suggested that post-HSCT care at home was feasible and safe.
• Outcomes were similar to outcomes in patients who do not receive post-HSCT care at home.
• The results were presented at ASH 2017 (Blood. 2017;130:745; https://bit.ly/2UelgVo).

Phase 2 trials: Microbiome, GVHD, and other outcomes

• With one phase 2 trial (NCT01725022), Dr. Sung and colleagues aim to determine if:
  • Patients can maintain their normal bowel microbiota by receiving post-HSCT care at home, as opposed to outpatient or inpatient care.
  • Treatment-related morbidities and mortality are similar between the groups.
  • Care at home improves quality of life and reduces costs.
• Trial details can be found here: https://bit.ly/2JRnY0Y.
  
  

• In the other phase 2 trial (NCT02218151), the main goal is to compare the incidence of grade 2-4 acute GVHD at 6 months in patients receiving care at home vs. inpatient or outpatient care.
  • The theory is that maintaining the microbiome will reduce the risk of GVHD.
  • A case of GVHD can add $100,000 to the cost of care, Dr. Sung noted.
• Trial details can be found here: https://bit.ly/32vr8y3.

COVID-19 and the microbiome

• Dr. Sung and colleagues are also conducting a trial of Lactobacillus rhamnosus GG (LGG) as prophylaxis for COVID-19 (NCT04399252).
• Research has shown that giving LGG to mice with Pseudomonas aeruginosa pneumonia can:
  • Help prevent lung injury and significantly improve survival (Shock. 2013;40[6]:496-503; https://bit.ly/3khQBRr).
  • Help modulate the microbiome and immune system, leading to decreased inflammation, TNF-alpha, IL-2, and IL-6, as well as increased regulatory T cells (Clin Nutr. 2017;36[6]:1549-1557; https://bit.ly/35lENJZ).
• Dr. Sung noted that TNF-alpha, IL-2, and IL-6 have also been implicated in COVID-19 and associated with increased lung injury.
• Dr. Sung and colleagues have theorized that LGG could decrease lung injury and the symptoms of COVID-19 and perhaps even prevent COVID-19.
• The researchers are conducting a randomized trial of LGG in household contacts of patients with COVID-19 (https://bit.ly/2GRSC9x).
• For more details on the trial, email [email protected] or visit https://bit.ly/2IsLjWh.

Disclosures:

Dr. Sung and Dr. Henry have no relevant disclosures. Duke's transplant trials are funded by grants from the National Institutes of Health. Funding for the COVID-19 trial is provided by the Duke Microbiome Center and philanthropic giving. The LGG and placebo used in the trial are provided by DSM.

* * *

For more MDedge podcasts, visit mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Hematology Oncology News: 

1. IMRT new standard of care for high-risk cervical cancer: https://bit.ly/3k7ji3y
2. Real-world results with checkpoint inhibitors found inferior to trial results: https://bit.ly/35cIt0v
3. Are HMAS appropriate for posttransplant maintenance in acute leukemias?: https://bit.ly/3lfqsE7
   
   

You can email the show at [email protected].