Blood & Cancer

New studies have shed additional light on how convalescent plasma may affect patients with COVID-19, how blood type impacts bleeding risk, the effects of race on cancer-associated thrombosis, and iron deficiency in pregnancy.

These studies were presented as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology.

Alisa S. Wolberg, PhD, of the University of North Carolina at Chapel Hill, who cochaired the session, reviews these studies with host David H. Henry, MD, in this episode.

Abstract #572: Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause. https://bit.ly/2Mc0R2A.

• This study, which included 422 patients, indicated that blood group O is overrepresented in patients with bleeding of unknown cause.
• Blood group O was associated with a more severe bleeding phenotype, especially oral mucosal bleeding, independent of the levels of von Willebrand factor and factor VIII.
• Patients with blood group O had increased clot density, but blood group O didn’t influence thrombin generation or platelet function analysis.
• The researchers said these findings are important for better understanding the underlying mechanisms of bleeding in patients who have bleeding of unknown cause.
• Dr. Wolberg said this study reframed how people look at bleeding of unknown cause.

Abstract #203: Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study. https://bit.ly/35Xi5HE.

• This study included more than 942,109 cancer patients.
• Results showed an independent association between race/ethnicity and the risk of cancer-associated thrombosis.
• Asians/Pacific Islanders had a significantly lower incidence of cancer-associated thrombosis, compared with non-Hispanic Whites.
• African Americans had a significantly higher incidence of cancer-associated thrombosis versus non-Hispanic Whites.
• Racial/ethnic differences were especially prominent when examining pulmonary embolism only.
• It’s hard to determine what causes these differences, Dr. Wolberg said. The differences could be explained by underlying biological traits, systemic racism, access to care, and/or the severity of underlying comorbidities, according to the researchers.

Abstract #424: Suboptimal Iron Deficiency Screening in Pregnancy in a High Resource Setting. https://bit.ly/2XYedSA.

• The study included data on 47,590 pregnancies in 44,552 women from Ontario.
• About 40% of these patients (n = 25,880) had ferritin measurements taken during pregnancy.
• Iron deficiency was observed in 52.8% of evaluable pregnancies, and severe iron deficiency was seen in 23.8%.
• These findings suggest a ferritin test should be included as part of routine bloodwork at the first prenatal visit, the researchers said.
• They also noted that failing to evaluate iron stores in the second and/or third trimester misses the periods of highest iron-deficiency risk, when intravenous iron may be considered.
• The researchers said these gaps in care should be addressed by revising guidelines.

Abstract #245: Efficacy of COVID-19 Pathogen-Inactivated Convalescent Plasma for Patients with Moderate-to-Severe Acute COVID-19: A Case-Matched Control Study. https://bit.ly/2XVlulU.

• For this study, researchers compared 15 cases and 30 controls, all of whom had COVID-19.
• Cases received two units of COVID-19 convalescent plasma (CCP) from different donors.
• CCP appeared to improve survival in hospitalized COVID patients, though the difference was not significant.
• The 28-day mortality rate was 6.7% among cases and 20.7% in controls (P = .233).
• The researchers also found that unselected CCPs have heterogeneous antivirus activity.
• Pathogen reduction treatment did not impact antivirus activity.
• ADAP, ACE2, RVPN, and COVAM could be used to define activity.
• A posttransfusion increase in activity could be detected in some, but not all, patients.
• The researchers said more definitive studies are needed.

*Some of the data presented at the meeting differ from data included in the abstracts.

Disclosures:

Dr. Wolberg disclosed relationships with Bristol-Myers Squibb, GlaxoSmithKline, and Takeda. Dr. Henry has no financial disclosures relevant to this episode.

*  *  *

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

New studies have shed additional light on how convalescent plasma may affect patients with COVID-19, how blood type impacts bleeding risk, the effects of race on cancer-associated thrombosis, and iron deficiency in pregnancy.

These studies were presented as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology.

Alisa S. Wolberg, PhD, of the University of North Carolina at Chapel Hill, who cochaired the session, reviews these studies with host David H. Henry, MD, in this episode.

Abstract #572: Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause. https://bit.ly/2Mc0R2A.

• This study, which included 422 patients, indicated that blood group O is overrepresented in patients with bleeding of unknown cause.
• Blood group O was associated with a more severe bleeding phenotype, especially oral mucosal bleeding, independent of the levels of von Willebrand factor and factor VIII.
• Patients with blood group O had increased clot density, but blood group O didn’t influence thrombin generation or platelet function analysis.
• The researchers said these findings are important for better understanding the underlying mechanisms of bleeding in patients who have bleeding of unknown cause.
• Dr. Wolberg said this study reframed how people look at bleeding of unknown cause.

Abstract #203: Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study. https://bit.ly/35Xi5HE.

• This study included more than 942,109 cancer patients.
• Results showed an independent association between race/ethnicity and the risk of cancer-associated thrombosis.
• Asians/Pacific Islanders had a significantly lower incidence of cancer-associated thrombosis, compared with non-Hispanic Whites.
• African Americans had a significantly higher incidence of cancer-associated thrombosis versus non-Hispanic Whites.
• Racial/ethnic differences were especially prominent when examining pulmonary embolism only.
• It’s hard to determine what causes these differences, Dr. Wolberg said. The differences could be explained by underlying biological traits, systemic racism, access to care, and/or the severity of underlying comorbidities, according to the researchers.

Abstract #424: Suboptimal Iron Deficiency Screening in Pregnancy in a High Resource Setting. https://bit.ly/2XYedSA.

• The study included data on 47,590 pregnancies in 44,552 women from Ontario.
• About 40% of these patients (n = 25,880) had ferritin measurements taken during pregnancy.
• Iron deficiency was observed in 52.8% of evaluable pregnancies, and severe iron deficiency was seen in 23.8%.
• These findings suggest a ferritin test should be included as part of routine bloodwork at the first prenatal visit, the researchers said.
• They also noted that failing to evaluate iron stores in the second and/or third trimester misses the periods of highest iron-deficiency risk, when intravenous iron may be considered.
• The researchers said these gaps in care should be addressed by revising guidelines.

Abstract #245: Efficacy of COVID-19 Pathogen-Inactivated Convalescent Plasma for Patients with Moderate-to-Severe Acute COVID-19: A Case-Matched Control Study. https://bit.ly/2XVlulU.

• For this study, researchers compared 15 cases and 30 controls, all of whom had COVID-19.
• Cases received two units of COVID-19 convalescent plasma (CCP) from different donors.
• CCP appeared to improve survival in hospitalized COVID patients, though the difference was not significant.
• The 28-day mortality rate was 6.7% among cases and 20.7% in controls (P = .233).
• The researchers also found that unselected CCPs have heterogeneous antivirus activity.
• Pathogen reduction treatment did not impact antivirus activity.
• ADAP, ACE2, RVPN, and COVAM could be used to define activity.
• A posttransfusion increase in activity could be detected in some, but not all, patients.
• The researchers said more definitive studies are needed.

*Some of the data presented at the meeting differ from data included in the abstracts.

Disclosures:

Dr. Wolberg disclosed relationships with Bristol-Myers Squibb, GlaxoSmithKline, and Takeda. Dr. Henry has no financial disclosures relevant to this episode.

*  *  *

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

Three studies revealed new findings on thrombosis in patients with cancer and/or COVID-19. These studies were presented at the 2020 annual meeting of the American Society of Hematology.

One study suggested the Khorana score may be ineffective for predicting venous thromboembolism (VTE) in cancer patients. Another study revealed factors that can predict VTE in patients with cancer and COVID-19. And a third study indicated that antithrombotic agents don’t improve outcomes in patients with severe COVID-19. 

Kristen M. Sanfilippo, MD, of Washington University, St. Louis, reviews these studies with host David H. Henry, MD, in this episode.

Abstract 202: Performance of Khorana Score to Predict One-Year Risk of Venous Thromboembolism in Over Two Million Patients With Cancer. https://bit.ly/3oCHOfQ.

• The study included 2,112,260 patients with cancer.
• At 1 year after diagnosis, 227,170 (10.8%) patients had developed VTE.
• The Khorana score was a weak to modest predictor of the 1-year risk of VTE (area under the curve, 0.565; 95% confidence interval, 0.564-0.566).

Abstract 204: Incidence of and Risk Factors for Venous Thromboembolism Among Hospitalized Patients With Cancer and COVID-19: Report From the COVID-19 and Cancer Consortium (CCC19) Registry. https://bit.ly/38waPnX.

• The study included 1,813 hospitalized patients with COVID-19 and cancer who were enrolled in the CCC19 registry.
• Patients had an increased risk of VTE if they had received anticancer therapy in the last 3 months (odds ratio, 1.63), had active disease (OR, 1.25 for stable/responding disease and 1.67 for progressing disease), had a cancer subtype with a high VTE risk (OR, 1.57 for high risk and 3.42 for very high risk), or were admitted to the ICU within 48 hours of hospitalization (OR, 2.38).
• Patients had a reduced risk of VTE if they received preadmission anticoagulant (OR, 0.80) or antiplatelet therapy (OR, 0.71).
• The researchers said this information will aid the development of a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19.
• For more information on the CCC19 registry, listen to the Blood & Cancer episode, “Studying cancer patients with COVID-19: NCCAPS and CCC19.” https://bit.ly/39lB0x0.

Abstract 206: Anticoagulant and Antiplatelet Use not Associated With Improvement in Severe Outcomes in COVID-19 Patients. https://bit.ly/3bvHqvV.

• This retrospective study included 28,076 patients with confirmed COVID-19 – 1,024 of whom were on antiplatelet agents, anticoagulants, or both.
• Chronic anticoagulant or antiplatelet use was not associated with a significantly lower risk of VTE (OR, 1.44), emergency department visit (OR, 0.94), ICU stay (OR, 0.87), or death (OR, 0.91).
• However, anticoagulant or antiplatelet use was associated with a decreased risk of ventilator use (OR, 0.72).
• Overall, these findings suggest chronic anticoagulant or antiplatelet use don't mitigate disease severity in COVID-19 patients, the researchers concluded.

The session in which these abstracts were presented is entitled, “904. Outcomes Research – Non-Malignant Conditions: Venous Thromboembolism Associated With Cancer and/or COVID-19,” and details can be found here: https://bit.ly/39olwIl.

Data in some of the abstracts differ from data presented at the meeting.

Disclosures

Dr. Sanfilippo disclosed relationships with Covington & Burling, Luther & Associates, Bayer, Health Services Advisory Group, and Amgen. 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

Three studies revealed new findings on thrombosis in patients with cancer and/or COVID-19. These studies were presented at the 2020 annual meeting of the American Society of Hematology.

One study suggested the Khorana score may be ineffective for predicting venous thromboembolism (VTE) in cancer patients. Another study revealed factors that can predict VTE in patients with cancer and COVID-19. And a third study indicated that antithrombotic agents don’t improve outcomes in patients with severe COVID-19. 

Kristen M. Sanfilippo, MD, of Washington University, St. Louis, reviews these studies with host David H. Henry, MD, in this episode.

Abstract 202: Performance of Khorana Score to Predict One-Year Risk of Venous Thromboembolism in Over Two Million Patients With Cancer. https://bit.ly/3oCHOfQ.

• The study included 2,112,260 patients with cancer.
• At 1 year after diagnosis, 227,170 (10.8%) patients had developed VTE.
• The Khorana score was a weak to modest predictor of the 1-year risk of VTE (area under the curve, 0.565; 95% confidence interval, 0.564-0.566).

Abstract 204: Incidence of and Risk Factors for Venous Thromboembolism Among Hospitalized Patients With Cancer and COVID-19: Report From the COVID-19 and Cancer Consortium (CCC19) Registry. https://bit.ly/38waPnX.

• The study included 1,813 hospitalized patients with COVID-19 and cancer who were enrolled in the CCC19 registry.
• Patients had an increased risk of VTE if they had received anticancer therapy in the last 3 months (odds ratio, 1.63), had active disease (OR, 1.25 for stable/responding disease and 1.67 for progressing disease), had a cancer subtype with a high VTE risk (OR, 1.57 for high risk and 3.42 for very high risk), or were admitted to the ICU within 48 hours of hospitalization (OR, 2.38).
• Patients had a reduced risk of VTE if they received preadmission anticoagulant (OR, 0.80) or antiplatelet therapy (OR, 0.71).
• The researchers said this information will aid the development of a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19.
• For more information on the CCC19 registry, listen to the Blood & Cancer episode, “Studying cancer patients with COVID-19: NCCAPS and CCC19.” https://bit.ly/39lB0x0.

Abstract 206: Anticoagulant and Antiplatelet Use not Associated With Improvement in Severe Outcomes in COVID-19 Patients. https://bit.ly/3bvHqvV.

• This retrospective study included 28,076 patients with confirmed COVID-19 – 1,024 of whom were on antiplatelet agents, anticoagulants, or both.
• Chronic anticoagulant or antiplatelet use was not associated with a significantly lower risk of VTE (OR, 1.44), emergency department visit (OR, 0.94), ICU stay (OR, 0.87), or death (OR, 0.91).
• However, anticoagulant or antiplatelet use was associated with a decreased risk of ventilator use (OR, 0.72).
• Overall, these findings suggest chronic anticoagulant or antiplatelet use don't mitigate disease severity in COVID-19 patients, the researchers concluded.

The session in which these abstracts were presented is entitled, “904. Outcomes Research – Non-Malignant Conditions: Venous Thromboembolism Associated With Cancer and/or COVID-19,” and details can be found here: https://bit.ly/39olwIl.

Data in some of the abstracts differ from data presented at the meeting.

Disclosures

Dr. Sanfilippo disclosed relationships with Covington & Burling, Luther & Associates, Bayer, Health Services Advisory Group, and Amgen. 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

A number of groundbreaking and practice-changing studies were presented at the San Antonio Breast Cancer Symposium 2020.

The RxPONDER, ADAPT, and PRIME-2 trials revealed patients who can forgo chemotherapy or radiotherapy, monarchE and PENELOPE-B showed conflicting results with CDK4/6 inhibitors, one study indicated that a new tool can guide adjuvant chemotherapy, and another study suggested that circulating tumor cells (CTCs) can predict overall survival (OS).

Alan P. Lyss, MD, subprincipal investigator for Heartland Cancer Research NCORP, joined host David H. Henry, MD, to discuss these and other studies — their top 10 presentations from SABCS 2020 — in this episode.

1. Abstract GS3-07. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort. https://bit.ly/2MGCVEH

• This presentation could be one of the most important stories to emerge from SABCS 2020, according to Dr. Lyss.
• The trial included 9,868 breast cancer patients who received radiotherapy over an 8-year period.
• Investigators compared patient and physician reports of toxicity during radiotherapy, assessing four symptoms: pain, pruritus, edema, and fatigue.
• Physicians under-recognized moderate to severe pain 30.9% of the time, pruritus 36.7% of the time, edema 51.4% of the time, and fatigue 18.8% of the time.
• “The bottom line is: We’ve got to do better at this, and the first step in correcting it is to acknowledge that there is a problem. This abstract established that,” Dr. Lyss said.

2. Abstract GS2-03. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/> 65 years with early invasive breast cancer: 10-year results. https://bit.ly/3omINAL

• The trial enrolled 1,326 women with histologically confirmed, unilateral invasive, hormone receptor-positive (HR+) breast cancer who were all 65 or older, had a tumor measuring 3 cm or less, had no nodal involvement, and were about to undergo breast-conserving surgery.
• The women were randomized 1:1 to receive adjuvant whole-breast irradiation or no radiotherapy in addition to adjuvant endocrine therapy.
• At 10 years, the rate of ipsilateral recurrence was significantly lower with radiotherapy than without it (0.9% vs 9.8%, P = .00008). The 10-year rate of regional recurrence was significantly lower with radiotherapy as well (0.5% vs. 2.3%, P = .014).
• There was no significant difference in the radiotherapy and no-radiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), non–breast cancer (8.7% vs. 10.2%, P = .41), metastasis-free survival (96.4% vs. 98.1%, P = .28), or OS (81.0% vs. 80.4%, P = .68).
• These results suggest radiotherapy could be omitted in this patient population, but the decision should be discussed and tailored to the individual patient, according to Dr. Henry.

3. Abstract GS1-01. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high-risk early breast cancer. https://bit.ly/38oSHwt

• The monarchE trial enrolled 5,637 women with HR+, HER2- early breast cancer.
  • Cohort 1 included patients with four or more positive nodes, up to three positive nodes and a tumor size ≥ 5 cm, or grade 3 disease.
  • Cohort 2 included women with up to three positive nodes and a Ki-67 index ≥ 20%.
• Patients in both cohorts were randomized to standard endocrine therapy alone or standard endocrine therapy with abemaciclib.
• The 2-year rate of invasive disease-free survival (IDFS) was 92.3% in the abemaciclib arm and 89.3% in the control arm (P = .0009). The 2-year distant relapse-free survival rate was 93.8% and 90.8%, respectively (P = .0009).
• Dr. Lyss said this is the first real advance in HR+ breast cancer adjuvant treatment in many years and has the potential to save thousands of lives. However, these are early data and should be interpreted with caution.

4. Abstract GS1-02. Phase III study of palbociclib combined with endocrine therapy (ET) in patients with hormone-receptor-positive (HR+), HER2-negative primary breast cancer and with high relapse risk after neoadjuvant chemotherapy (NACT): First results from PENELOPE-B. https://bit.ly/2XeQvRs

• The PENELOPE-B trial enrolled 1,250 women who had completed neoadjuvant chemotherapy and locoregional therapy.
• They were randomized to palbociclib plus endocrine therapy or endocrine therapy plus placebo.
• There was no significant difference in IDFS with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or 4 years (73% vs. 72.4%).

5. Abstract GS4-10. Development and validation of a tool integrating the 21-gene recurrence score and clinicopathologic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer. https://bit.ly/38htoMD

• The RSClin tool integrates the 21-gene recurrence score and clinicopathologic features, including the grade of the tumor, the tumor size, and the patient's age.
• Researchers found that RSClin could guide adjuvant chemotherapy in HR+, HER2-, axillary node-negative breast cancer with greater precision, when compared with  clinicopathologic features or genomic data alone.
• RSClin is available at https://online.genomichealth.com/.

6. Abstract GS4-08. Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data. https://bit.ly/2MGUrZp

• This study included 4,079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements in previous trials.
• The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether those levels were associated with OS.
• The median OS was 47 months for patients who were CTC-negative at both baseline and follow-up, 32.2 months for patients who were positive at baseline and negative at follow-up, 29.6 months for patients who were negative at baseline and positive at follow-up, and 17.8 months for patients who were positive at both time points.
• With the negative-negative group as the reference, hazard ratios were 1.52 for the positive-negative group, 1.74 for the negative-positive group, and 3.15 for the positive-positive group (P < .0001 for all).

7. Abstract GS3-00. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). https://bit.ly/35bK7Px

• RxPONDER included 5,083 adults with HR+, HER2- breast cancer, one to three positive nodes, no contraindications to taxane and/or anthracycline-based chemotherapy, and recurrence scores of 25 or below.
• Patients were randomized 1:1 to receive endocrine therapy or chemo-endocrine therapy using three stratification factors: recurrence score (0-13 vs.14-25), menopausal status, and axillary nodal dissection vs. sentinel node biopsy.
• At a median follow-up of 5.1 years, there was no association between chemotherapy benefit and recurrence score values in the whole study population.
• In postmenopausal patients, there was no difference in 5-year IDFS between patients who received chemotherapy and those who didn’t (91.6% vs. 91.9%, P = .82).
• However, in premenopausal patients, the 5-year IDFS rate was 94.2% with chemotherapy and 89% without it (P = .0004).
• The data also showed an OS benefit with chemotherapy in premenopausal patients (P = .032), although this result is considered early due to few deaths at the time of evaluation.
• “These data really establish that postmenopausal women with between one to three involved nodes and an Oncotype DX score of 25 or less do not need post-operative adjuvant chemotherapy; end of discussion,” Dr. Lyss said. “For physicians who have been giving those women chemotherapy, these data are immediately practice- changing.”

8. Abstract GS4-04. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score <26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial. https://bit.ly/35edjVY

• In this phase 3 trial, researchers combined static biomarkers (recurrence score in baseline core biopsy) and dynamic biomarkers (Ki-67 response) in an attempt to optimize adjuvant therapy in lumi

In this episode, we bring you clips from the best Blood & Cancer shows of 2020. Blood & Cancer will be back with new episodes in 2021. 

1. ESMO 2020: Late-breaking and practice-changing studies on COVID-19 and breast, lung, gastrointestinal, and other cancers
   https://bit.ly/3h7aWZM
   
   
2. Beyond the lungs: How COVID-19 affects the blood, brain, gastrointestinal system, and other organ systems
   https://bit.ly/37GhV8Q
   
   
3. EHA25: AML, myeloma, polycythemia vera, and COVID-19 with EHA President John Gribben
   https://bit.ly/3nS4592
   
   
4. VTE rate, 'COVID toes,' and Virchow's triad: What you need to know about COVID and coagulation
   https://bit.ly/3rizmnM
   
   
5. ASCO 2020: Practice-changing studies in breast, lung, colorectal, and other cancers
   https://bit.ly/37EIbkg

* * *

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

News from SABCS 2020:

1. RxPONDER: Even more women may forgo chemo for breast cancer: https://bit.ly/2LIYjZt
2. Breast surgery may be a gateway to addictive medication use: https://bit.ly/3gSWfJF
3. Pregnancy after breast cancer is rockier but doesn’t increase recurrence risk: https://bit.ly/2KwlhCx

Email Blood & Cancer at [email protected]. 

The ASH Research Collaborative COVID-19 Registry for Hematology was established earlier this year to study patients with hematologic malignancies diagnosed with COVID-19. Now, the registry also includes patients with nonmalignant hematologic disorders and hematologic manifestations of COVID-19.

William Wood, MD, of the University of North Carolina at Chapel Hill, recently presented data from the registry at the ASH Annual Meeting. In this episode, Dr. Wood tells host David H. Henry, MD, how the registry came to be and reviews some of its findings.

About the registry

• The registry is part of the ASH Research Collaborative, an organization established in 2018 to foster collaboration to accelerate progress in hematology.
• The registry houses data on patients with a COVID-19 diagnosis and hematologic disorders/malignancies or hematologic manifestations of COVID-19.
• Health care providers around the world can contribute data to the registry.
• Anyone can view summaries of the deidentified data on the registry website.
• The website data are updated every day or every few days.
• The information compiled in the registry includes:
  • The nature of patients’ underlying disease
  • Treatments received until COVID-19 diagnosis
  • Sociodemographic information
  • COVID-19 symptoms and time to resolution or death
  • COVID-19–directed treatments
  • Expected prognosis
  • Whether patients opted for intensive care.

Registry findings

• The registry data presented at ASH 2020 included 656 patients with hematologic malignancies and COVID-19.
• Dr. Wood said the first conclusion drawn from these data is that patients with underlying hematologic malignancies are a “medically vulnerable population” when it comes to COVID-19.
• The mortality rate was 20% overall and 33% in patients with hospitalization-level severity.
• The other major finding, Dr. Wood said, is that the risk of severe COVID-19 and death is differentially distributed.
• Risk factors for adverse COVID-19 outcomes include:
  • Increasing age
  • Advanced underlying disease or limited prognosis
  • Forgoing intensive management.
    
    

Relevant links

• ASH Research Collaborative: https://bit.ly/37pczyV.
• COVID-19 Registry for Hematology: https://bit.ly/3r1U9vO.
• Blood Adv. 2020. 4(23):5966-75. https://bit.ly/34jWVTt.
• Wood W et al. ASH 2020, Abstract 215. https://bit.ly/3gRzw0A.

Disclosures

Dr. Wood disclosed research funding from Pfizer, consultancy for Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. 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

News from ASH 2020:

1. No benefit from tranexamic acid prophylaxis in blood cancers: https://bit.ly/2K3Mah1
2. ‘Practice changing’: Ruxolitinib as second-line in chronic GVHD: https://bit.ly/3gT4kyg 
3. Durable responses with anti-BCMA CAR T-cell for multiple myeloma: https://bit.ly/381f1ut
4. Five-minute SC injection of daratumumab in RRMM: https://bit.ly/3gKuZgx

Email Blood & Cancer at [email protected]

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.

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