Key clinical point: Mutation in isocitrate dehydrogenase 2 (IDH2) gene predicted a favorable response to daunorubicin, cytarabine, and cladribine (DAC) regimen in patients with normal karyotype acute myeloid leukemia (NK-AML).

Major finding: IDH2 mutation had a positive impact on overall survival in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Study details: Findings are from a retrospective analysis of 398 patients with NK-AML (IDH2⁺, n=50) treated with DA (48%), DAC (44%), or DA+fludarabine (8%) regimens.

Disclosures: This study was supported by grants from the Polish Ministry of Science and Education, Polish National Center for Research and Development, and Nicolaus Copernicus University in Bydgoszcz. The authors declared no conflicts of interest.

Source: Libura M et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88120-y.

Key clinical point: Mutation in isocitrate dehydrogenase 2 (IDH2) gene predicted a favorable response to daunorubicin, cytarabine, and cladribine (DAC) regimen in patients with normal karyotype acute myeloid leukemia (NK-AML).

Major finding: IDH2 mutation had a positive impact on overall survival in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Study details: Findings are from a retrospective analysis of 398 patients with NK-AML (IDH2⁺, n=50) treated with DA (48%), DAC (44%), or DA+fludarabine (8%) regimens.

Disclosures: This study was supported by grants from the Polish Ministry of Science and Education, Polish National Center for Research and Development, and Nicolaus Copernicus University in Bydgoszcz. The authors declared no conflicts of interest.

Source: Libura M et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88120-y.

Key clinical point: Mutation in isocitrate dehydrogenase 2 (IDH2) gene predicted a favorable response to daunorubicin, cytarabine, and cladribine (DAC) regimen in patients with normal karyotype acute myeloid leukemia (NK-AML).

Major finding: IDH2 mutation had a positive impact on overall survival in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Study details: Findings are from a retrospective analysis of 398 patients with NK-AML (IDH2⁺, n=50) treated with DA (48%), DAC (44%), or DA+fludarabine (8%) regimens.

Disclosures: This study was supported by grants from the Polish Ministry of Science and Education, Polish National Center for Research and Development, and Nicolaus Copernicus University in Bydgoszcz. The authors declared no conflicts of interest.

Source: Libura M et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88120-y.

Key clinical point: In patients with newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML) evolving from myeloproliferative neoplasms (MPNs), treatment with venetoclax-based (VEN-b) regimens led to modest clinical responses with no substantial improvement in survival, but high treatment-associated hematologic toxicity and mortality.

Major finding: Median overall survival from initiation of VEN-b regimen was 4 (95% confidence interval, 2-8) months with 8-week mortality being 32%. Only 7 patients with newly diagnosed AML achieved a response, with 3 achieving complete remission, 3 achieving complete remission with incomplete count recovery, and 1 achieving partial remission. Grade 3 or higher infections were observed in 84% of patients during the initial treatment cycle, with severe hemorrhagic complications in 45% of patients.

Study details: Findings are from a retrospective analysis of 31 patients with newly diagnosed (n=14) or R/R (n=17) post-MPN-AML who were treated with VEN-b therapies.

Disclosures: This study was supported partly by a Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health to MD Anderson Cancer Center. Some investigators reported financial and nonfinancial ties with various pharmaceutical companies.

Source: Masarova L et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020003934.

Key clinical point: In patients with newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML) evolving from myeloproliferative neoplasms (MPNs), treatment with venetoclax-based (VEN-b) regimens led to modest clinical responses with no substantial improvement in survival, but high treatment-associated hematologic toxicity and mortality.

Major finding: Median overall survival from initiation of VEN-b regimen was 4 (95% confidence interval, 2-8) months with 8-week mortality being 32%. Only 7 patients with newly diagnosed AML achieved a response, with 3 achieving complete remission, 3 achieving complete remission with incomplete count recovery, and 1 achieving partial remission. Grade 3 or higher infections were observed in 84% of patients during the initial treatment cycle, with severe hemorrhagic complications in 45% of patients.

Study details: Findings are from a retrospective analysis of 31 patients with newly diagnosed (n=14) or R/R (n=17) post-MPN-AML who were treated with VEN-b therapies.

Disclosures: This study was supported partly by a Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health to MD Anderson Cancer Center. Some investigators reported financial and nonfinancial ties with various pharmaceutical companies.

Source: Masarova L et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020003934.

Key clinical point: In patients with newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML) evolving from myeloproliferative neoplasms (MPNs), treatment with venetoclax-based (VEN-b) regimens led to modest clinical responses with no substantial improvement in survival, but high treatment-associated hematologic toxicity and mortality.

Major finding: Median overall survival from initiation of VEN-b regimen was 4 (95% confidence interval, 2-8) months with 8-week mortality being 32%. Only 7 patients with newly diagnosed AML achieved a response, with 3 achieving complete remission, 3 achieving complete remission with incomplete count recovery, and 1 achieving partial remission. Grade 3 or higher infections were observed in 84% of patients during the initial treatment cycle, with severe hemorrhagic complications in 45% of patients.

Study details: Findings are from a retrospective analysis of 31 patients with newly diagnosed (n=14) or R/R (n=17) post-MPN-AML who were treated with VEN-b therapies.

Disclosures: This study was supported partly by a Cancer Center Support Grant from the National Cancer Institute, National Institutes of Health to MD Anderson Cancer Center. Some investigators reported financial and nonfinancial ties with various pharmaceutical companies.

Source: Masarova L et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020003934.

Key clinical point: Treatment with a combination of hypomethylating agents (HMA) and venetoclax (VEN) was similarly effective in patients with acute myeloid leukemia (AML) with or without spliceosome mutations with specific mutational pairs demonstrating favorable outcomes.

Major finding: Overall response rate (89% vs. 79%; P = .32), composite complete response (79% vs. 75%; P = .65), and median overall survival (OS; 35 vs. 14 months; P = .58) were not significantly different in patients with vs. without spliceosome mutations. Co-occurrence of IDH2 and SRSF2 mutations was associated with favorable outcomes (1- and 2-year OS, 100% and 88%, respectively).

Study details: Findings are from a retrospective study of 119 adult patients with AML treated with frontline HMA+VEN-based therapy. Mutation in the spliceosome gene was observed in 39 patients.

Disclosures: No specific funding source was identified. Some investigators reported research funding, support, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Lachowiez CA et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020004173.

Key clinical point: Treatment with a combination of hypomethylating agents (HMA) and venetoclax (VEN) was similarly effective in patients with acute myeloid leukemia (AML) with or without spliceosome mutations with specific mutational pairs demonstrating favorable outcomes.

Major finding: Overall response rate (89% vs. 79%; P = .32), composite complete response (79% vs. 75%; P = .65), and median overall survival (OS; 35 vs. 14 months; P = .58) were not significantly different in patients with vs. without spliceosome mutations. Co-occurrence of IDH2 and SRSF2 mutations was associated with favorable outcomes (1- and 2-year OS, 100% and 88%, respectively).

Study details: Findings are from a retrospective study of 119 adult patients with AML treated with frontline HMA+VEN-based therapy. Mutation in the spliceosome gene was observed in 39 patients.

Disclosures: No specific funding source was identified. Some investigators reported research funding, support, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Lachowiez CA et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020004173.

Key clinical point: Treatment with a combination of hypomethylating agents (HMA) and venetoclax (VEN) was similarly effective in patients with acute myeloid leukemia (AML) with or without spliceosome mutations with specific mutational pairs demonstrating favorable outcomes.

Major finding: Overall response rate (89% vs. 79%; P = .32), composite complete response (79% vs. 75%; P = .65), and median overall survival (OS; 35 vs. 14 months; P = .58) were not significantly different in patients with vs. without spliceosome mutations. Co-occurrence of IDH2 and SRSF2 mutations was associated with favorable outcomes (1- and 2-year OS, 100% and 88%, respectively).

Study details: Findings are from a retrospective study of 119 adult patients with AML treated with frontline HMA+VEN-based therapy. Mutation in the spliceosome gene was observed in 39 patients.

Disclosures: No specific funding source was identified. Some investigators reported research funding, support, honoraria, consultancy, and advisory roles for various pharmaceutical companies.

Source: Lachowiez CA et al. Blood Adv. 2021 Apr 22. doi: 10.1182/bloodadvances.2020004173.

Key clinical point: Low-intensity chemotherapy with clofarabine or cladribine and low-dose cytarabine (LDAC) alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML).

Major finding: Overall, response was observed in 66% of patients, with complete remission (CR) and CR with incomplete count recovery in 59% and 7% of patients, respectively. The 4- and 8-week mortality was low at 2% and 11%, respectively. During median follow-up of 60 months, the median overall survival was 12.5 months.

Study details: This study assessed 248 older patients (median age, 69 years) with newly diagnosed AML who were treated with either clofarabine (n=119) or cladribine (n=129) combined with LDAC alternating with decitabine.

Disclosures: This study was funded by the MD Anderson Cancer Center Support and the Charif Souki Cancer Research Fund. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Am J Hematol. 2021 Apr 26. doi: 10.1002/ajh.26206.

Key clinical point: Low-intensity chemotherapy with clofarabine or cladribine and low-dose cytarabine (LDAC) alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML).

Major finding: Overall, response was observed in 66% of patients, with complete remission (CR) and CR with incomplete count recovery in 59% and 7% of patients, respectively. The 4- and 8-week mortality was low at 2% and 11%, respectively. During median follow-up of 60 months, the median overall survival was 12.5 months.

Study details: This study assessed 248 older patients (median age, 69 years) with newly diagnosed AML who were treated with either clofarabine (n=119) or cladribine (n=129) combined with LDAC alternating with decitabine.

Disclosures: This study was funded by the MD Anderson Cancer Center Support and the Charif Souki Cancer Research Fund. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Am J Hematol. 2021 Apr 26. doi: 10.1002/ajh.26206.

Key clinical point: Low-intensity chemotherapy with clofarabine or cladribine and low-dose cytarabine (LDAC) alternating with decitabine was effective and safe for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML).

Major finding: Overall, response was observed in 66% of patients, with complete remission (CR) and CR with incomplete count recovery in 59% and 7% of patients, respectively. The 4- and 8-week mortality was low at 2% and 11%, respectively. During median follow-up of 60 months, the median overall survival was 12.5 months.

Study details: This study assessed 248 older patients (median age, 69 years) with newly diagnosed AML who were treated with either clofarabine (n=119) or cladribine (n=129) combined with LDAC alternating with decitabine.

Disclosures: This study was funded by the MD Anderson Cancer Center Support and the Charif Souki Cancer Research Fund. Some investigators including the lead author reported ties with various pharmaceutical companies.

Source: Kadia TM et al. Am J Hematol. 2021 Apr 26. doi: 10.1002/ajh.26206.

Key clinical point: In patients with relapsed/refractory acute myeloid leukemia (AML), mivebresib (MIV) was tolerated and showed antileukemic activity as monotherapy (MIV-mono) and in combination with venetoclax (MIV-Ven).

Major finding: In the MIV-mono cohort, response included complete remission with incomplete blood count recovery (5%) and resistant disease (79%). In patients receiving MIV-Ven, responses were complete remission (7%), partial remission (7%), leukemia-free state (7%), resistant disease (40%), and aplasia (3%). Treatment-emergent adverse events (TEAEs) were reported in 100% of patients, with serious TEAEs in 74%, 88%, and 40% of patients in MIV-mono, MIV-Ven, and patients who switched from MIV-mono to MIV-Ven groups, respectively.

Study details: Findings are from phase 1 study including 44 adult patients with relapsed/refractory AML who received either MIV-mono (n=19) or MIV-Ven (n=25). Because of disease progression, 5 patients switched from MIV-mono to MIV-Ven.

Disclosures: This study was funded by AbbVie. Investigators including the lead author reported ties with various pharmaceutical companies including AbbVie.

Source: Borthakur G et al. Cancer. 2021 May 2. doi: 10.1002/cncr.33590.

Key clinical point: In patients with relapsed/refractory acute myeloid leukemia (AML), mivebresib (MIV) was tolerated and showed antileukemic activity as monotherapy (MIV-mono) and in combination with venetoclax (MIV-Ven).

Major finding: In the MIV-mono cohort, response included complete remission with incomplete blood count recovery (5%) and resistant disease (79%). In patients receiving MIV-Ven, responses were complete remission (7%), partial remission (7%), leukemia-free state (7%), resistant disease (40%), and aplasia (3%). Treatment-emergent adverse events (TEAEs) were reported in 100% of patients, with serious TEAEs in 74%, 88%, and 40% of patients in MIV-mono, MIV-Ven, and patients who switched from MIV-mono to MIV-Ven groups, respectively.

Study details: Findings are from phase 1 study including 44 adult patients with relapsed/refractory AML who received either MIV-mono (n=19) or MIV-Ven (n=25). Because of disease progression, 5 patients switched from MIV-mono to MIV-Ven.

Disclosures: This study was funded by AbbVie. Investigators including the lead author reported ties with various pharmaceutical companies including AbbVie.

Source: Borthakur G et al. Cancer. 2021 May 2. doi: 10.1002/cncr.33590.

Key clinical point: In patients with relapsed/refractory acute myeloid leukemia (AML), mivebresib (MIV) was tolerated and showed antileukemic activity as monotherapy (MIV-mono) and in combination with venetoclax (MIV-Ven).

Major finding: In the MIV-mono cohort, response included complete remission with incomplete blood count recovery (5%) and resistant disease (79%). In patients receiving MIV-Ven, responses were complete remission (7%), partial remission (7%), leukemia-free state (7%), resistant disease (40%), and aplasia (3%). Treatment-emergent adverse events (TEAEs) were reported in 100% of patients, with serious TEAEs in 74%, 88%, and 40% of patients in MIV-mono, MIV-Ven, and patients who switched from MIV-mono to MIV-Ven groups, respectively.

Study details: Findings are from phase 1 study including 44 adult patients with relapsed/refractory AML who received either MIV-mono (n=19) or MIV-Ven (n=25). Because of disease progression, 5 patients switched from MIV-mono to MIV-Ven.

Disclosures: This study was funded by AbbVie. Investigators including the lead author reported ties with various pharmaceutical companies including AbbVie.

Source: Borthakur G et al. Cancer. 2021 May 2. doi: 10.1002/cncr.33590.

Key clinical point: Addition of tosedostat to low-dose cytosine arabinoside (LDAC) did not confer any additional clinical benefit compared with LDAC alone in older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy.

Major finding: There was no significant benefit of adding tosedostat to LDAC vs. LDAC alone on overall response (25% vs. 18%; P = .22) and 2-year overall survival (16% vs. 12%; P = .8). Overall rates of grade 3 or higher toxicity were low, but diarrhea and cardiac toxicity were significantly higher with tosedostat.

Study details: Findings are from LI-1 trial including 243 older (age, 60 years or older) patients with de novo or secondary AML or high-risk myelodysplastic syndrome who were unfit for intensive chemotherapy. Patients were randomly allocated to receive either LDAC (n=121) or LDAC+tosedostat (n=122).

Disclosures: This study was supported by CTI Biopharma, Blood Cancer UK, the Haematology Clinical Trials Unit, and the Centre for Trials Research, Cardiff University. No author disclosures were reported.

Source: Dennis M et al. Br J Haematol. 2021 May 7. doi: 10.1111/bjh.17501.

Key clinical point: Addition of tosedostat to low-dose cytosine arabinoside (LDAC) did not confer any additional clinical benefit compared with LDAC alone in older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy.

Major finding: There was no significant benefit of adding tosedostat to LDAC vs. LDAC alone on overall response (25% vs. 18%; P = .22) and 2-year overall survival (16% vs. 12%; P = .8). Overall rates of grade 3 or higher toxicity were low, but diarrhea and cardiac toxicity were significantly higher with tosedostat.

Study details: Findings are from LI-1 trial including 243 older (age, 60 years or older) patients with de novo or secondary AML or high-risk myelodysplastic syndrome who were unfit for intensive chemotherapy. Patients were randomly allocated to receive either LDAC (n=121) or LDAC+tosedostat (n=122).

Disclosures: This study was supported by CTI Biopharma, Blood Cancer UK, the Haematology Clinical Trials Unit, and the Centre for Trials Research, Cardiff University. No author disclosures were reported.

Source: Dennis M et al. Br J Haematol. 2021 May 7. doi: 10.1111/bjh.17501.

Key clinical point: Addition of tosedostat to low-dose cytosine arabinoside (LDAC) did not confer any additional clinical benefit compared with LDAC alone in older patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy.

Major finding: There was no significant benefit of adding tosedostat to LDAC vs. LDAC alone on overall response (25% vs. 18%; P = .22) and 2-year overall survival (16% vs. 12%; P = .8). Overall rates of grade 3 or higher toxicity were low, but diarrhea and cardiac toxicity were significantly higher with tosedostat.

Study details: Findings are from LI-1 trial including 243 older (age, 60 years or older) patients with de novo or secondary AML or high-risk myelodysplastic syndrome who were unfit for intensive chemotherapy. Patients were randomly allocated to receive either LDAC (n=121) or LDAC+tosedostat (n=122).

Disclosures: This study was supported by CTI Biopharma, Blood Cancer UK, the Haematology Clinical Trials Unit, and the Centre for Trials Research, Cardiff University. No author disclosures were reported.

Source: Dennis M et al. Br J Haematol. 2021 May 7. doi: 10.1111/bjh.17501.

Key clinical point: In the absence of human leukocyte antigen-matched donors, allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) with posttransplant cyclophosphamide (PTCy) yielded better survival outcomes vs. cord blood transplantation (CBT) in patients with acute myeloid leukemia (AML).

Major finding: CBT was associated with a significantly higher risk for nonrelapse mortality (adjusted hazard ratio [aHR], 2.09), worse leukemia-free survival (aHR, 1.68), and overall survival (aHR, 1.70) vs. MMUD (all P less than .0001).

Study details: This study included adult patients with AML who underwent a first allo-HCT using CBT (n=902) or single-allele MMUD with PTCy (n=280) between 2010 and 2019.

Disclosures: No funding source was disclosed. The authors declared no conflicts of interest.

Source: Dholaria B et al. J Hematol Oncol. 2021 May 3. doi: 10.1186/s13045-021-01086-2.

Key clinical point: In the absence of human leukocyte antigen-matched donors, allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) with posttransplant cyclophosphamide (PTCy) yielded better survival outcomes vs. cord blood transplantation (CBT) in patients with acute myeloid leukemia (AML).

Major finding: CBT was associated with a significantly higher risk for nonrelapse mortality (adjusted hazard ratio [aHR], 2.09), worse leukemia-free survival (aHR, 1.68), and overall survival (aHR, 1.70) vs. MMUD (all P less than .0001).

Study details: This study included adult patients with AML who underwent a first allo-HCT using CBT (n=902) or single-allele MMUD with PTCy (n=280) between 2010 and 2019.

Disclosures: No funding source was disclosed. The authors declared no conflicts of interest.

Source: Dholaria B et al. J Hematol Oncol. 2021 May 3. doi: 10.1186/s13045-021-01086-2.

Key clinical point: In the absence of human leukocyte antigen-matched donors, allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) with posttransplant cyclophosphamide (PTCy) yielded better survival outcomes vs. cord blood transplantation (CBT) in patients with acute myeloid leukemia (AML).

Major finding: CBT was associated with a significantly higher risk for nonrelapse mortality (adjusted hazard ratio [aHR], 2.09), worse leukemia-free survival (aHR, 1.68), and overall survival (aHR, 1.70) vs. MMUD (all P less than .0001).

Study details: This study included adult patients with AML who underwent a first allo-HCT using CBT (n=902) or single-allele MMUD with PTCy (n=280) between 2010 and 2019.

Disclosures: No funding source was disclosed. The authors declared no conflicts of interest.

Source: Dholaria B et al. J Hematol Oncol. 2021 May 3. doi: 10.1186/s13045-021-01086-2.

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

Several studies published this month have shed some more light on the treatment and prognosis of certain molecular subgroups such as FLT3, spliceasome mutations and IDH mutation. A study from MD Anderson Cancer Center (MDACC) demonstrated the efficacy of FLT33 inhibitors in the treatment of patients with very low allelic burden. Patients who recived both a FMS-like tyrosine kinase inhibitor (FLT3i) during induction and an allogeneic HCT at time of first remission had better 5 year overall survival (OS) (100%) than those who received neither (27%). The 5-year OS rate among patients who did not receive FLT3i-based induction but underwent allo-SCT in CR1 was 71%. None of the patients who received a FLT3i had detectable FLT3 at time of relapse, compared to 67% for those who did not. The main weakness of the study is the small number of patients (total of 50 patients). This study however does provide some provocative data regarding the validity of the FLT3 allelic ratio in decisions regarding treatment and prognosis. The results of this study need to be validated in a larger cohort of patients.

A study by Lachowiez et al, further refined the prognostic significance of spliceosome mutations in patients treated with ven + HMA. Of the 119 patients, 39 had spliceosome mutations. The overall response and prognosis was not different between patients with and without spliceosome mutations. However, SRSF2 was associated with IDH2 mutation and the median OS was not reached vs, patient with U2AF1 who had a higher association with RAS mutations (OS 8 months). The prognostic role of standard cytotoxic chemotherapy in improving the outcome of patients with an IDH mutation was studied by the group. In a re-evaluation of the randomized trial comparing the addition of fludarabine or cladrbaine to standard 7 +3, 50 patients with an IDH mutation were evaluated. Patients with an IDH mutation who received cladribine. IDH2 mutation had a positive impact on OS in patients treated with DAC regimen (54% vs. 33%; P = .0087) but not in those treated with daunorubicin+cytarabine (DA; 21% vs. 23%; P = .22) regimen. Moreover, DAC induction was independently associated with a reduced risk for death when the observations were censored at allogeneic hematopoietic stem cell transplant (hazard ratio, 0.21; P = .02).

Although hypomethylating agents + venetoclax (HMA +ven) have shown efficacy in multiple patient subgroups, the outcome of patients with post-MPN acute myeloid leukemia (AML) remains poor even with HMA + ven. In a retrospective study, 31 patients with post MPN AML were treated with HMA + ven. The overall survival for patients with relapsed post MPN AML was 3 months with none of the 9 patients achieving a CR/CRi. As for the patients with previously untreated post MPN-AML, the median survival was still poor at 8 months with 43% achieving CR/CRi. This study highlights the large unmet need in this patient population. In comparison, in a retrospective study by Piccini et al, of the 47 patients with relapsed/refractory (R/R) AML treated with venetoclax based regimens the composite CR rate was 55%. These outcomes are similar to other studies of venetoclax based regimens in patients with R/R AML. 

In a retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) registry, the outcomes of patients receiving mismatched unrelated donor (MMUD) with post transplant cyclophosphamide (PTCy) had better outcomes compared to patients receiving cord blood transplantation (CBT). The 2 year leukemia free survival (LFS) for CBT vs MMUD was 42.8% vs 60.5% and OS was 46.85 vs 62.8%. This retrospective study demonstrated that PTCy can improve the outcomes of patients receiving of MMUD (Dholaria B et al. J Hematol Oncol. 2021 May).

To decrease the incidence and prevalence of hepatitis C virus (HCV) in the United States, hepatology experts, public health officials, and patient advocates agree that linkage to care is essential for treatment of people who inject drugs (PWID). The most recent surveillance report from the Centers for Disease Control and Prevention (CDC) estimates that injection drug use accounts for the transmission of approximately 72% of new HCV infections.^1,2

Although recent studies of direct-acting antiviral (DAA) agents have not been designed to investigate the long-term rates of reinfection in this population, various population-based studies in multiple countries have attempted to describe the rate of reinfection for this cohort.^3-7 This rate varies widely based on the defined population of PWID, definition of reinfection, and the prevalence of HCV in a given PWID population. However, studies have consistently shown a relatively low historic rate of reinfection, which varies from 1 to 5 per 100 person-years in patients who have ever injected drugs, to 3 to 33 per 100 person-years in patients who continue injection drug use (IDU). Higher rates are found in those who engage in high-risk behaviors such as needle sharing.^3-7 Yet, the US opioid crisis is attributable to a recent rise in both overall incidence and reinfections, highlighting the importance of determining the best treatment strategy for those who become reinfected.¹

Current HCV guidelines from the American Association for the Study of Liver Diseases AASLD) and Infectious Diseases Society of America (IDSA) encourage access to retreatment for PWID who become reinfected, stating that new reinfections should follow treatment-naïve therapy recommendations.⁸ However, to date this recommendation has not been validated by published clinical trials or patient case reports. This is likely due in part both to the small number of reinfections among PWID requiring retreatment and barriers to payment for treatment, particularly for individuals with substance use disorders.⁹ While this recommendation can be found under the key population section for the “Identification and Management of HCV in People Who Inject Drugs,” health care providers (HCPs) may easily miss this statement if they alternatively refer to the “Treatment-Experienced” section that recommends escalation to either sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir in patients who are NS5A inhibitor DAA-experienced.⁸ Anecdotally, the first instinct for many HCPs when considering a treatment regimen for a reinfected patient is to refer to treatment-experienced regimen recommendations rather than appreciating the reinfected virus to be treatment naïve.

A treatment-escalation approach could have the consequence of limiting the number of times a patient could undergo treatment on successive reinfections. Additionally, these retreatment regimens often are more expensive, resulting in further cost barriers for payors approving retreatment for individuals with HCV reinfection. In contrast, demonstrating efficacy of a less costly short-course regimen would support increased access to initial and retreatment courses for PWID. The implications of enabling improved access to care is essential in the setting of the ongoing opioid epidemic in the United States.

Given the perspective that the virus should be considered treatment naïve for patients who become reinfected, we describe here 3 cases of patients previously achieving sustained virologic response (SVR) being retreated with the cost-effective 8-week regimen of ledipasvir/sofosbuvir following reinfection.

Case Reports

Case 1

A 59-year-old male presented for his third treatment course for HCV genotype 1a. The patient initially underwent 76 weeks of interferon-based HCV treatment in 2007 and 2008, from which he was determined to have achieved SVR in 24 weeks (SVR24) in April 2009. His viral load remained undetected through February 2010 but subsequently had detectable virus again in 2011 following relapsed use of alcohol, cocaine, and injection drugs. The patient elected to await approval of DAAs and eventually completed an 8-week regimen of ledipasvir/sofosbuvir from May to July 2016, achieving SVR24 in December 2016. The patient’s viral load was rechecked in October 2018 and he was again viremic following recent IDU, suggesting a second reinfection.

In preparation for his third HCV treatment, the patient was included in shared decision making to consider retreating his de novo infection as treatment naïve to provide a briefer (ie, 8 weeks) and more cost-effective treatment given his low likelihood of advanced fibrotic liver disease—his FibroScan score was 6.5 kPa, whereas scores ≥ 12.5 kPa in patients with chronic HCV suggest a higher likelihood of cirrhosis.¹⁰ At week 4, the patient’s viral load was undetected, he completed his 8-week regimen of ledipasvir/sofosbuvir as planned and achieved SVR12 (Table). He had reported excellent adherence throughout treatment with assistance of a pill box and validated by a reported pill count.

Case 2

A 32-year-old male presented with HCV genotype 1a. Like case 1, this patient had a low FibroScan score of 4.7 kPa. He was previously infected with genotype 3 and completed a 12-week course of sofosbuvir/velpatasvir in November 2016. He achieved SVR12 as evidenced by an undetected viral load in February 2017 despite questionable adherence throughout and relapsed use of heroin by the end of his regimen. He continued intermittent IDU and presented in October 2018 with a detectable viral load, now with genotype 1a. The patient similarly agreed to undergo an 8-week regimen of ledipasvir/sofosbuvir, considering his de novo infection to be treatment naïve. His viral load at treatment week 3 was quantitatively negative while qualitatively detectable at < 15 U/mL. He completed his treatment course in March 2019 and was determined to have achieved SVR24 in September 2019.

Case 3

A 51-year-old male presented with a history of HCV genotype 1a and a low FibroScan score (4.9 kPa ). The patient was previously infected with genotype 2 and had achieved SVR24 following a 12-week regimen of sofosbuvir/velpatasvir in 2017. The patient subsequently was reinfected with genotype 1a and completed an 8-week course of ledipasvir/sofosbuvir in May 2019. The patient had his SVR12 lab drawn 9 days early and was undetectable at that time. He reported 0 missed doses during treatment and achieved an undetected viral load by treatment week 4.

Discussion

We demonstrate that HCV reinfection after treatment with previous interferon and/or DAA-based regimens can be treated with less costly 8-week treatment regimens. Current guidelines include a statement allowing for reinfected patients to follow initial treatment guidelines, but this statement has previously lacked published evidence and may be overlooked by HCPs who refer to recommendations for treatment-experienced patients. Given the increasing likelihood of HCPs encountering patients who have become reinfected with HCV after achieving SVR from a DAA regimen, further delineation may be needed in the recommendations for treatment-experienced patients to highlight the important nuance of recognizing that reinfections should follow initial treatment guidance.

While all 3 of these cases met criteria for the least costly and simplest 1 pill once daily 8-week regimen of ledipasvir/sofosbuvir, patients requiring retreatment with alternative genotypes or evidence of advanced fibrotic liver disease could benefit from a similar approach of using the least expensive and/or shortest duration regimen for which they meet eligibility. With this approach, coverage could be further expanded to the PWID population to help limit HCV transmission amid the opioid crisis.¹

Studies have established that PWID are able to achieve similar SVR efficacy rates similar to that of the general population when treated in the setting of an interdisciplinary treatment team that offers collaborative management of complex psychosocial comorbidities and harm reduction strategies.^11,12 These integrative patient-centric strategies may include personalized behavioral health pretreatment evaluations, access to substance use treatment, harm reduction counseling, needle exchange programs, and close follow-up by a case manager.^2,13 Current DAA regimens combined with 1 or more of these strategies have demonstrated SVR12 rates of 90 to 95% for initial treatment regimens.¹¹ These high SVR12 rates were even achieved in a recent study in which 74% (76/103) of participants had self-reported IDU within 30 days of HCV treatment start and similar IDU rates throughout treatment.¹² A meta-analysis, including real-world studies of DAA treatment outcomes yielded a pooled SVR of 88% (95% CI, 83‐92%) for recent PWID and 91% (95% CI, 88‐95%) for individuals using opiate substitution therapy (OST).¹⁴ Additionally, linking PWID with OST also reduces risk for reinfection.^14,15

For any patient with detectable HCV after completing the initial DAA regimen, it is important to distinguish between relapse and reinfection. SVR12 is generally synonymous with a clinical cure. Patients with ongoing risk factors posttreatment should continue to have their HCV viral load monitored for evidence of reinfection. Patients without known risk factors may benefit from repeat viral load only if there is clinical concern for reinfection, for example, a rise in liver enzymes.

We have shown that patients with ongoing risk factors who are reinfected can be treated successfully with cost-effective 8-week regimens. For comparison this 8-week regimen of ledipasvir/sofosbuvir has an average wholesale price (AWP) of $28,800, while alternative regimens approved for treatment-naïve patients vary in AWP from $31,680 to $43,200, and regimens approved for retreatment of DAA failures have an AWP as high as $89,712.

An 8-week treatment regimen for both initial and reinfection regimens affords many advantages in medication adherence and both medication and provider resource cost-effectiveness. First, new HCV reinfections are disproportionally younger individuals often with complex psychosocial issues that impact retention in treatment. An 8-week course of treatment can be initiated concurrently with substance abuse treatment programs, including intensive outpatient programs and residential treatment programs that are usually at least 28 days. Many of these programs provide aftercare options that would extend the entire course of treatment. These opportunities afford individuals to receive HCV treatment in a setting that supports medication adherence, sobriety efforts, and education on harm reduction to reduce risk for reinfection.

Finally, statistical models indicate eradication of HCV will require scaling up the treatment of PWID in conjunction with harm reduction strategies such as OST and needle exchange programs.¹⁶ In contrast, there are low risks associated with retreatment given these medications are well-tolerated, treatment of PWID lowers the risk of further HCV transmission, and the understanding of these reinfections being treatment naïve disavows concerns of these patients having resistance to regimens that cleared their prior infections. The opportunity to provide retreatment without escalating regimen complexity or cost increases access to care for a vulnerable population while aiding in the eradication of HCV.

To decrease the incidence and prevalence of hepatitis C virus (HCV) in the United States, hepatology experts, public health officials, and patient advocates agree that linkage to care is essential for treatment of people who inject drugs (PWID). The most recent surveillance report from the Centers for Disease Control and Prevention (CDC) estimates that injection drug use accounts for the transmission of approximately 72% of new HCV infections.^1,2

Although recent studies of direct-acting antiviral (DAA) agents have not been designed to investigate the long-term rates of reinfection in this population, various population-based studies in multiple countries have attempted to describe the rate of reinfection for this cohort.^3-7 This rate varies widely based on the defined population of PWID, definition of reinfection, and the prevalence of HCV in a given PWID population. However, studies have consistently shown a relatively low historic rate of reinfection, which varies from 1 to 5 per 100 person-years in patients who have ever injected drugs, to 3 to 33 per 100 person-years in patients who continue injection drug use (IDU). Higher rates are found in those who engage in high-risk behaviors such as needle sharing.^3-7 Yet, the US opioid crisis is attributable to a recent rise in both overall incidence and reinfections, highlighting the importance of determining the best treatment strategy for those who become reinfected.¹

Current HCV guidelines from the American Association for the Study of Liver Diseases AASLD) and Infectious Diseases Society of America (IDSA) encourage access to retreatment for PWID who become reinfected, stating that new reinfections should follow treatment-naïve therapy recommendations.⁸ However, to date this recommendation has not been validated by published clinical trials or patient case reports. This is likely due in part both to the small number of reinfections among PWID requiring retreatment and barriers to payment for treatment, particularly for individuals with substance use disorders.⁹ While this recommendation can be found under the key population section for the “Identification and Management of HCV in People Who Inject Drugs,” health care providers (HCPs) may easily miss this statement if they alternatively refer to the “Treatment-Experienced” section that recommends escalation to either sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir in patients who are NS5A inhibitor DAA-experienced.⁸ Anecdotally, the first instinct for many HCPs when considering a treatment regimen for a reinfected patient is to refer to treatment-experienced regimen recommendations rather than appreciating the reinfected virus to be treatment naïve.

A treatment-escalation approach could have the consequence of limiting the number of times a patient could undergo treatment on successive reinfections. Additionally, these retreatment regimens often are more expensive, resulting in further cost barriers for payors approving retreatment for individuals with HCV reinfection. In contrast, demonstrating efficacy of a less costly short-course regimen would support increased access to initial and retreatment courses for PWID. The implications of enabling improved access to care is essential in the setting of the ongoing opioid epidemic in the United States.

Given the perspective that the virus should be considered treatment naïve for patients who become reinfected, we describe here 3 cases of patients previously achieving sustained virologic response (SVR) being retreated with the cost-effective 8-week regimen of ledipasvir/sofosbuvir following reinfection.

Case Reports

Case 1

A 59-year-old male presented for his third treatment course for HCV genotype 1a. The patient initially underwent 76 weeks of interferon-based HCV treatment in 2007 and 2008, from which he was determined to have achieved SVR in 24 weeks (SVR24) in April 2009. His viral load remained undetected through February 2010 but subsequently had detectable virus again in 2011 following relapsed use of alcohol, cocaine, and injection drugs. The patient elected to await approval of DAAs and eventually completed an 8-week regimen of ledipasvir/sofosbuvir from May to July 2016, achieving SVR24 in December 2016. The patient’s viral load was rechecked in October 2018 and he was again viremic following recent IDU, suggesting a second reinfection.

In preparation for his third HCV treatment, the patient was included in shared decision making to consider retreating his de novo infection as treatment naïve to provide a briefer (ie, 8 weeks) and more cost-effective treatment given his low likelihood of advanced fibrotic liver disease—his FibroScan score was 6.5 kPa, whereas scores ≥ 12.5 kPa in patients with chronic HCV suggest a higher likelihood of cirrhosis.¹⁰ At week 4, the patient’s viral load was undetected, he completed his 8-week regimen of ledipasvir/sofosbuvir as planned and achieved SVR12 (Table). He had reported excellent adherence throughout treatment with assistance of a pill box and validated by a reported pill count.

Case 2

A 32-year-old male presented with HCV genotype 1a. Like case 1, this patient had a low FibroScan score of 4.7 kPa. He was previously infected with genotype 3 and completed a 12-week course of sofosbuvir/velpatasvir in November 2016. He achieved SVR12 as evidenced by an undetected viral load in February 2017 despite questionable adherence throughout and relapsed use of heroin by the end of his regimen. He continued intermittent IDU and presented in October 2018 with a detectable viral load, now with genotype 1a. The patient similarly agreed to undergo an 8-week regimen of ledipasvir/sofosbuvir, considering his de novo infection to be treatment naïve. His viral load at treatment week 3 was quantitatively negative while qualitatively detectable at < 15 U/mL. He completed his treatment course in March 2019 and was determined to have achieved SVR24 in September 2019.

Case 3

A 51-year-old male presented with a history of HCV genotype 1a and a low FibroScan score (4.9 kPa ). The patient was previously infected with genotype 2 and had achieved SVR24 following a 12-week regimen of sofosbuvir/velpatasvir in 2017. The patient subsequently was reinfected with genotype 1a and completed an 8-week course of ledipasvir/sofosbuvir in May 2019. The patient had his SVR12 lab drawn 9 days early and was undetectable at that time. He reported 0 missed doses during treatment and achieved an undetected viral load by treatment week 4.

Discussion

We demonstrate that HCV reinfection after treatment with previous interferon and/or DAA-based regimens can be treated with less costly 8-week treatment regimens. Current guidelines include a statement allowing for reinfected patients to follow initial treatment guidelines, but this statement has previously lacked published evidence and may be overlooked by HCPs who refer to recommendations for treatment-experienced patients. Given the increasing likelihood of HCPs encountering patients who have become reinfected with HCV after achieving SVR from a DAA regimen, further delineation may be needed in the recommendations for treatment-experienced patients to highlight the important nuance of recognizing that reinfections should follow initial treatment guidance.

While all 3 of these cases met criteria for the least costly and simplest 1 pill once daily 8-week regimen of ledipasvir/sofosbuvir, patients requiring retreatment with alternative genotypes or evidence of advanced fibrotic liver disease could benefit from a similar approach of using the least expensive and/or shortest duration regimen for which they meet eligibility. With this approach, coverage could be further expanded to the PWID population to help limit HCV transmission amid the opioid crisis.¹

Studies have established that PWID are able to achieve similar SVR efficacy rates similar to that of the general population when treated in the setting of an interdisciplinary treatment team that offers collaborative management of complex psychosocial comorbidities and harm reduction strategies.^11,12 These integrative patient-centric strategies may include personalized behavioral health pretreatment evaluations, access to substance use treatment, harm reduction counseling, needle exchange programs, and close follow-up by a case manager.^2,13 Current DAA regimens combined with 1 or more of these strategies have demonstrated SVR12 rates of 90 to 95% for initial treatment regimens.¹¹ These high SVR12 rates were even achieved in a recent study in which 74% (76/103) of participants had self-reported IDU within 30 days of HCV treatment start and similar IDU rates throughout treatment.¹² A meta-analysis, including real-world studies of DAA treatment outcomes yielded a pooled SVR of 88% (95% CI, 83‐92%) for recent PWID and 91% (95% CI, 88‐95%) for individuals using opiate substitution therapy (OST).¹⁴ Additionally, linking PWID with OST also reduces risk for reinfection.^14,15

For any patient with detectable HCV after completing the initial DAA regimen, it is important to distinguish between relapse and reinfection. SVR12 is generally synonymous with a clinical cure. Patients with ongoing risk factors posttreatment should continue to have their HCV viral load monitored for evidence of reinfection. Patients without known risk factors may benefit from repeat viral load only if there is clinical concern for reinfection, for example, a rise in liver enzymes.

We have shown that patients with ongoing risk factors who are reinfected can be treated successfully with cost-effective 8-week regimens. For comparison this 8-week regimen of ledipasvir/sofosbuvir has an average wholesale price (AWP) of $28,800, while alternative regimens approved for treatment-naïve patients vary in AWP from $31,680 to $43,200, and regimens approved for retreatment of DAA failures have an AWP as high as $89,712.

An 8-week treatment regimen for both initial and reinfection regimens affords many advantages in medication adherence and both medication and provider resource cost-effectiveness. First, new HCV reinfections are disproportionally younger individuals often with complex psychosocial issues that impact retention in treatment. An 8-week course of treatment can be initiated concurrently with substance abuse treatment programs, including intensive outpatient programs and residential treatment programs that are usually at least 28 days. Many of these programs provide aftercare options that would extend the entire course of treatment. These opportunities afford individuals to receive HCV treatment in a setting that supports medication adherence, sobriety efforts, and education on harm reduction to reduce risk for reinfection.

Finally, statistical models indicate eradication of HCV will require scaling up the treatment of PWID in conjunction with harm reduction strategies such as OST and needle exchange programs.¹⁶ In contrast, there are low risks associated with retreatment given these medications are well-tolerated, treatment of PWID lowers the risk of further HCV transmission, and the understanding of these reinfections being treatment naïve disavows concerns of these patients having resistance to regimens that cleared their prior infections. The opportunity to provide retreatment without escalating regimen complexity or cost increases access to care for a vulnerable population while aiding in the eradication of HCV.

To decrease the incidence and prevalence of hepatitis C virus (HCV) in the United States, hepatology experts, public health officials, and patient advocates agree that linkage to care is essential for treatment of people who inject drugs (PWID). The most recent surveillance report from the Centers for Disease Control and Prevention (CDC) estimates that injection drug use accounts for the transmission of approximately 72% of new HCV infections.^1,2

Although recent studies of direct-acting antiviral (DAA) agents have not been designed to investigate the long-term rates of reinfection in this population, various population-based studies in multiple countries have attempted to describe the rate of reinfection for this cohort.^3-7 This rate varies widely based on the defined population of PWID, definition of reinfection, and the prevalence of HCV in a given PWID population. However, studies have consistently shown a relatively low historic rate of reinfection, which varies from 1 to 5 per 100 person-years in patients who have ever injected drugs, to 3 to 33 per 100 person-years in patients who continue injection drug use (IDU). Higher rates are found in those who engage in high-risk behaviors such as needle sharing.^3-7 Yet, the US opioid crisis is attributable to a recent rise in both overall incidence and reinfections, highlighting the importance of determining the best treatment strategy for those who become reinfected.¹

Current HCV guidelines from the American Association for the Study of Liver Diseases AASLD) and Infectious Diseases Society of America (IDSA) encourage access to retreatment for PWID who become reinfected, stating that new reinfections should follow treatment-naïve therapy recommendations.⁸ However, to date this recommendation has not been validated by published clinical trials or patient case reports. This is likely due in part both to the small number of reinfections among PWID requiring retreatment and barriers to payment for treatment, particularly for individuals with substance use disorders.⁹ While this recommendation can be found under the key population section for the “Identification and Management of HCV in People Who Inject Drugs,” health care providers (HCPs) may easily miss this statement if they alternatively refer to the “Treatment-Experienced” section that recommends escalation to either sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir in patients who are NS5A inhibitor DAA-experienced.⁸ Anecdotally, the first instinct for many HCPs when considering a treatment regimen for a reinfected patient is to refer to treatment-experienced regimen recommendations rather than appreciating the reinfected virus to be treatment naïve.

A treatment-escalation approach could have the consequence of limiting the number of times a patient could undergo treatment on successive reinfections. Additionally, these retreatment regimens often are more expensive, resulting in further cost barriers for payors approving retreatment for individuals with HCV reinfection. In contrast, demonstrating efficacy of a less costly short-course regimen would support increased access to initial and retreatment courses for PWID. The implications of enabling improved access to care is essential in the setting of the ongoing opioid epidemic in the United States.

Given the perspective that the virus should be considered treatment naïve for patients who become reinfected, we describe here 3 cases of patients previously achieving sustained virologic response (SVR) being retreated with the cost-effective 8-week regimen of ledipasvir/sofosbuvir following reinfection.

Case Reports

Case 1

A 59-year-old male presented for his third treatment course for HCV genotype 1a. The patient initially underwent 76 weeks of interferon-based HCV treatment in 2007 and 2008, from which he was determined to have achieved SVR in 24 weeks (SVR24) in April 2009. His viral load remained undetected through February 2010 but subsequently had detectable virus again in 2011 following relapsed use of alcohol, cocaine, and injection drugs. The patient elected to await approval of DAAs and eventually completed an 8-week regimen of ledipasvir/sofosbuvir from May to July 2016, achieving SVR24 in December 2016. The patient’s viral load was rechecked in October 2018 and he was again viremic following recent IDU, suggesting a second reinfection.

In preparation for his third HCV treatment, the patient was included in shared decision making to consider retreating his de novo infection as treatment naïve to provide a briefer (ie, 8 weeks) and more cost-effective treatment given his low likelihood of advanced fibrotic liver disease—his FibroScan score was 6.5 kPa, whereas scores ≥ 12.5 kPa in patients with chronic HCV suggest a higher likelihood of cirrhosis.¹⁰ At week 4, the patient’s viral load was undetected, he completed his 8-week regimen of ledipasvir/sofosbuvir as planned and achieved SVR12 (Table). He had reported excellent adherence throughout treatment with assistance of a pill box and validated by a reported pill count.

Case 2

A 32-year-old male presented with HCV genotype 1a. Like case 1, this patient had a low FibroScan score of 4.7 kPa. He was previously infected with genotype 3 and completed a 12-week course of sofosbuvir/velpatasvir in November 2016. He achieved SVR12 as evidenced by an undetected viral load in February 2017 despite questionable adherence throughout and relapsed use of heroin by the end of his regimen. He continued intermittent IDU and presented in October 2018 with a detectable viral load, now with genotype 1a. The patient similarly agreed to undergo an 8-week regimen of ledipasvir/sofosbuvir, considering his de novo infection to be treatment naïve. His viral load at treatment week 3 was quantitatively negative while qualitatively detectable at < 15 U/mL. He completed his treatment course in March 2019 and was determined to have achieved SVR24 in September 2019.

Case 3

A 51-year-old male presented with a history of HCV genotype 1a and a low FibroScan score (4.9 kPa ). The patient was previously infected with genotype 2 and had achieved SVR24 following a 12-week regimen of sofosbuvir/velpatasvir in 2017. The patient subsequently was reinfected with genotype 1a and completed an 8-week course of ledipasvir/sofosbuvir in May 2019. The patient had his SVR12 lab drawn 9 days early and was undetectable at that time. He reported 0 missed doses during treatment and achieved an undetected viral load by treatment week 4.

Discussion

We demonstrate that HCV reinfection after treatment with previous interferon and/or DAA-based regimens can be treated with less costly 8-week treatment regimens. Current guidelines include a statement allowing for reinfected patients to follow initial treatment guidelines, but this statement has previously lacked published evidence and may be overlooked by HCPs who refer to recommendations for treatment-experienced patients. Given the increasing likelihood of HCPs encountering patients who have become reinfected with HCV after achieving SVR from a DAA regimen, further delineation may be needed in the recommendations for treatment-experienced patients to highlight the important nuance of recognizing that reinfections should follow initial treatment guidance.

While all 3 of these cases met criteria for the least costly and simplest 1 pill once daily 8-week regimen of ledipasvir/sofosbuvir, patients requiring retreatment with alternative genotypes or evidence of advanced fibrotic liver disease could benefit from a similar approach of using the least expensive and/or shortest duration regimen for which they meet eligibility. With this approach, coverage could be further expanded to the PWID population to help limit HCV transmission amid the opioid crisis.¹

Studies have established that PWID are able to achieve similar SVR efficacy rates similar to that of the general population when treated in the setting of an interdisciplinary treatment team that offers collaborative management of complex psychosocial comorbidities and harm reduction strategies.^11,12 These integrative patient-centric strategies may include personalized behavioral health pretreatment evaluations, access to substance use treatment, harm reduction counseling, needle exchange programs, and close follow-up by a case manager.^2,13 Current DAA regimens combined with 1 or more of these strategies have demonstrated SVR12 rates of 90 to 95% for initial treatment regimens.¹¹ These high SVR12 rates were even achieved in a recent study in which 74% (76/103) of participants had self-reported IDU within 30 days of HCV treatment start and similar IDU rates throughout treatment.¹² A meta-analysis, including real-world studies of DAA treatment outcomes yielded a pooled SVR of 88% (95% CI, 83‐92%) for recent PWID and 91% (95% CI, 88‐95%) for individuals using opiate substitution therapy (OST).¹⁴ Additionally, linking PWID with OST also reduces risk for reinfection.^14,15

For any patient with detectable HCV after completing the initial DAA regimen, it is important to distinguish between relapse and reinfection. SVR12 is generally synonymous with a clinical cure. Patients with ongoing risk factors posttreatment should continue to have their HCV viral load monitored for evidence of reinfection. Patients without known risk factors may benefit from repeat viral load only if there is clinical concern for reinfection, for example, a rise in liver enzymes.

We have shown that patients with ongoing risk factors who are reinfected can be treated successfully with cost-effective 8-week regimens. For comparison this 8-week regimen of ledipasvir/sofosbuvir has an average wholesale price (AWP) of $28,800, while alternative regimens approved for treatment-naïve patients vary in AWP from $31,680 to $43,200, and regimens approved for retreatment of DAA failures have an AWP as high as $89,712.

An 8-week treatment regimen for both initial and reinfection regimens affords many advantages in medication adherence and both medication and provider resource cost-effectiveness. First, new HCV reinfections are disproportionally younger individuals often with complex psychosocial issues that impact retention in treatment. An 8-week course of treatment can be initiated concurrently with substance abuse treatment programs, including intensive outpatient programs and residential treatment programs that are usually at least 28 days. Many of these programs provide aftercare options that would extend the entire course of treatment. These opportunities afford individuals to receive HCV treatment in a setting that supports medication adherence, sobriety efforts, and education on harm reduction to reduce risk for reinfection.

Finally, statistical models indicate eradication of HCV will require scaling up the treatment of PWID in conjunction with harm reduction strategies such as OST and needle exchange programs.¹⁶ In contrast, there are low risks associated with retreatment given these medications are well-tolerated, treatment of PWID lowers the risk of further HCV transmission, and the understanding of these reinfections being treatment naïve disavows concerns of these patients having resistance to regimens that cleared their prior infections. The opportunity to provide retreatment without escalating regimen complexity or cost increases access to care for a vulnerable population while aiding in the eradication of HCV.