Hematology Times

The PROBE (Patient Reported Outcomes Burdens and Experience) questionnaire was found to be a valid instrument to evaluate health status in patients with hemophilia in an cross‐cultural context, according to an international study.

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“This study [aimed] to investigate the variation in the PROBE questionnaire–driven measurements across four broad geographical regions,” wrote Chatree Chai‐Adisaksopha, MD, of McMaster University in Hamilton, Ontario, and his colleagues. The results of the study were published in Haemophilia.

The researchers analyzed data from 862 study participants who resided in various geographical regions, including North America, South America, Europe, and the Western Pacific. The majority of participants were male and had greater than 12 years of education.

The team assessed common characteristics of participants through collection of demographic data, including age, gender, years of education, among others. With respect to hemophilia, they evaluated patient‐reported outcome measures across these four regions.

“Outcome measurement in haemophilia has been developed to capture clinically relevant outcomes like bleeding rates, pharmacokinetics, joint pain, joint function scores, radiologic changes and mortality rates,” the researchers wrote.

After analysis, Dr. Chai‐Adisaksopha and his colleagues found that the PROBE questionnaire showed low variability when used on a multinational, cross‐cultural level. In particular, limited variation was found with respect to years of education and geographical region in all subcategories, with the exception of mobility score. In contrast, diagnosis and age had the highest levels of variation.

Region contributed 0.26% of variance in the PROBE score. Similarly, education level contributed 0.34% of the variance. However, age contributed 3.42% and diagnosis contributed 22.42% of the variance in the PROBE score.

The authors acknowledged a key limitation of the study was the inability to include all geographical regions, largely due to an inadequate number of participants in certain areas, such as Africa.

“Despite being used in disparate groups of patients, in 14 countries, in four regions and in 20 languages, the tool produced comparable results, suggesting it can be reliably used across these groups,” the researchers wrote.

The study was funded by Baxalta, Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, and Sobi, with additional support from the U.S. National Hemophilia Foundation. Co-author Mark W. Skinner is the principal investigator and no other investigators reported relevant conflicts of interest.

SOURCE: Chai-Adisaksopha C et al. Haemophilia. 2019 Mar 12. doi: 10.1111/hae.13703 .

The PROBE (Patient Reported Outcomes Burdens and Experience) questionnaire was found to be a valid instrument to evaluate health status in patients with hemophilia in an cross‐cultural context, according to an international study.

PeopleImages/gettyimages

“This study [aimed] to investigate the variation in the PROBE questionnaire–driven measurements across four broad geographical regions,” wrote Chatree Chai‐Adisaksopha, MD, of McMaster University in Hamilton, Ontario, and his colleagues. The results of the study were published in Haemophilia.

The researchers analyzed data from 862 study participants who resided in various geographical regions, including North America, South America, Europe, and the Western Pacific. The majority of participants were male and had greater than 12 years of education.

The team assessed common characteristics of participants through collection of demographic data, including age, gender, years of education, among others. With respect to hemophilia, they evaluated patient‐reported outcome measures across these four regions.

“Outcome measurement in haemophilia has been developed to capture clinically relevant outcomes like bleeding rates, pharmacokinetics, joint pain, joint function scores, radiologic changes and mortality rates,” the researchers wrote.

After analysis, Dr. Chai‐Adisaksopha and his colleagues found that the PROBE questionnaire showed low variability when used on a multinational, cross‐cultural level. In particular, limited variation was found with respect to years of education and geographical region in all subcategories, with the exception of mobility score. In contrast, diagnosis and age had the highest levels of variation.

Region contributed 0.26% of variance in the PROBE score. Similarly, education level contributed 0.34% of the variance. However, age contributed 3.42% and diagnosis contributed 22.42% of the variance in the PROBE score.

The authors acknowledged a key limitation of the study was the inability to include all geographical regions, largely due to an inadequate number of participants in certain areas, such as Africa.

“Despite being used in disparate groups of patients, in 14 countries, in four regions and in 20 languages, the tool produced comparable results, suggesting it can be reliably used across these groups,” the researchers wrote.

The study was funded by Baxalta, Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, and Sobi, with additional support from the U.S. National Hemophilia Foundation. Co-author Mark W. Skinner is the principal investigator and no other investigators reported relevant conflicts of interest.

SOURCE: Chai-Adisaksopha C et al. Haemophilia. 2019 Mar 12. doi: 10.1111/hae.13703 .

The PROBE (Patient Reported Outcomes Burdens and Experience) questionnaire was found to be a valid instrument to evaluate health status in patients with hemophilia in an cross‐cultural context, according to an international study.

PeopleImages/gettyimages

“This study [aimed] to investigate the variation in the PROBE questionnaire–driven measurements across four broad geographical regions,” wrote Chatree Chai‐Adisaksopha, MD, of McMaster University in Hamilton, Ontario, and his colleagues. The results of the study were published in Haemophilia.

The researchers analyzed data from 862 study participants who resided in various geographical regions, including North America, South America, Europe, and the Western Pacific. The majority of participants were male and had greater than 12 years of education.

The team assessed common characteristics of participants through collection of demographic data, including age, gender, years of education, among others. With respect to hemophilia, they evaluated patient‐reported outcome measures across these four regions.

“Outcome measurement in haemophilia has been developed to capture clinically relevant outcomes like bleeding rates, pharmacokinetics, joint pain, joint function scores, radiologic changes and mortality rates,” the researchers wrote.

After analysis, Dr. Chai‐Adisaksopha and his colleagues found that the PROBE questionnaire showed low variability when used on a multinational, cross‐cultural level. In particular, limited variation was found with respect to years of education and geographical region in all subcategories, with the exception of mobility score. In contrast, diagnosis and age had the highest levels of variation.

Region contributed 0.26% of variance in the PROBE score. Similarly, education level contributed 0.34% of the variance. However, age contributed 3.42% and diagnosis contributed 22.42% of the variance in the PROBE score.

The authors acknowledged a key limitation of the study was the inability to include all geographical regions, largely due to an inadequate number of participants in certain areas, such as Africa.

“Despite being used in disparate groups of patients, in 14 countries, in four regions and in 20 languages, the tool produced comparable results, suggesting it can be reliably used across these groups,” the researchers wrote.

The study was funded by Baxalta, Bayer, Bioverativ, CSL Behring, Novo Nordisk, Roche, and Sobi, with additional support from the U.S. National Hemophilia Foundation. Co-author Mark W. Skinner is the principal investigator and no other investigators reported relevant conflicts of interest.

SOURCE: Chai-Adisaksopha C et al. Haemophilia. 2019 Mar 12. doi: 10.1111/hae.13703 .

Prolonged exposure to ibrutinib showed sustained progression-free and overall survival and had tolerable safety outcomes in patients with relapsed or refractory chronic lymphocytic leukemia, according to a post hoc analysis of the phase 3 RESONATE trial.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

“This study ... provides further evidence for efficacy and safety with prolonged treatment across multiple high-risk genomic and clinical disease features and with increasing depth of response,” John C. Byrd, MD, of the Ohio State University, Columbus, and his colleagues wrote in Blood.

RESONATE included 391 high-risk patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Study participants were randomized in a 1:1 fashion to receive ibrutinib 420 mg daily or ofatumumab (initial infusion of 300 mg followed by seven weekly infusions and four monthly infusions of 2,000 mg) for a maximum of 24 weeks. Drug therapy was continued until cancer progression or intolerable toxicity of either agent was seen.

“Primary analysis at median follow-up of 9.7 months demonstrated superiority of ibrutinib over ofatumumab in PFS [progression-free survival], OS [overall survival], and overall response,” the researchers wrote. “With extended follow-up of median 44 months, these same results persist; a plateau of PFS has not yet been reached in this long-term follow-up. We also observe very durable remissions among patients of all genomic groups, including those with del(17)(p13.1), del(11)(q22.3), or unmutated IgHV [immunoglobulin heavy chain gene], who are traditionally considered high-risk populations.”

After an extended follow-up (median, 44 months), the team found that the PFS benefit with ibrutinib was sustained, compared with ofatumumab (hazard ratio, 0.133; 95% confidence interval, 0.099-0.178; P less than .0001). The 3-year PFS rate was 59% for ibrutinib, compared with 3% for ofatumumab. Similar PFS benefits were seen among subgroups of high- and very high–risk patients, based on their scores on the International Prognostic Index for CLL.

The OS benefit was also sustained in those randomized to ibrutinib (HR, 0.591; 95% CI, 0.378-0.926; P = .0208). The continued OS benefit with ibrutinib versus ofatumumab continued even after a sensitivity analysis adjusted for crossover of patients to ibrutinib.

With respect to safety, adverse events of any grade were similar to previous reports of ibrutinib. In fact, the prevalence of adverse events (grade 3 or higher) decreased over time for participants that continued on ibrutinib.

“Multiple studies are ongoing to investigate ibrutinib earlier in the course of CLL therapy, including phase 3 studies of first-line ibrutinib [or ibrutinib combined with anti-CD20 therapy], compared with standard chemoimmunotherapy regimens,” they wrote.

The study was sponsored by Pharmacyclics and Janssen. The authors reported financial disclosures related to the sponsors and several other companies.

SOURCE: Byrd JC et al. Blood. 2019 Mar 6. doi: 10.1182/blood-2018-08-870238.

Prolonged exposure to ibrutinib showed sustained progression-free and overall survival and had tolerable safety outcomes in patients with relapsed or refractory chronic lymphocytic leukemia, according to a post hoc analysis of the phase 3 RESONATE trial.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

“This study ... provides further evidence for efficacy and safety with prolonged treatment across multiple high-risk genomic and clinical disease features and with increasing depth of response,” John C. Byrd, MD, of the Ohio State University, Columbus, and his colleagues wrote in Blood.

RESONATE included 391 high-risk patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Study participants were randomized in a 1:1 fashion to receive ibrutinib 420 mg daily or ofatumumab (initial infusion of 300 mg followed by seven weekly infusions and four monthly infusions of 2,000 mg) for a maximum of 24 weeks. Drug therapy was continued until cancer progression or intolerable toxicity of either agent was seen.

“Primary analysis at median follow-up of 9.7 months demonstrated superiority of ibrutinib over ofatumumab in PFS [progression-free survival], OS [overall survival], and overall response,” the researchers wrote. “With extended follow-up of median 44 months, these same results persist; a plateau of PFS has not yet been reached in this long-term follow-up. We also observe very durable remissions among patients of all genomic groups, including those with del(17)(p13.1), del(11)(q22.3), or unmutated IgHV [immunoglobulin heavy chain gene], who are traditionally considered high-risk populations.”

After an extended follow-up (median, 44 months), the team found that the PFS benefit with ibrutinib was sustained, compared with ofatumumab (hazard ratio, 0.133; 95% confidence interval, 0.099-0.178; P less than .0001). The 3-year PFS rate was 59% for ibrutinib, compared with 3% for ofatumumab. Similar PFS benefits were seen among subgroups of high- and very high–risk patients, based on their scores on the International Prognostic Index for CLL.

The OS benefit was also sustained in those randomized to ibrutinib (HR, 0.591; 95% CI, 0.378-0.926; P = .0208). The continued OS benefit with ibrutinib versus ofatumumab continued even after a sensitivity analysis adjusted for crossover of patients to ibrutinib.

With respect to safety, adverse events of any grade were similar to previous reports of ibrutinib. In fact, the prevalence of adverse events (grade 3 or higher) decreased over time for participants that continued on ibrutinib.

“Multiple studies are ongoing to investigate ibrutinib earlier in the course of CLL therapy, including phase 3 studies of first-line ibrutinib [or ibrutinib combined with anti-CD20 therapy], compared with standard chemoimmunotherapy regimens,” they wrote.

The study was sponsored by Pharmacyclics and Janssen. The authors reported financial disclosures related to the sponsors and several other companies.

SOURCE: Byrd JC et al. Blood. 2019 Mar 6. doi: 10.1182/blood-2018-08-870238.

Prolonged exposure to ibrutinib showed sustained progression-free and overall survival and had tolerable safety outcomes in patients with relapsed or refractory chronic lymphocytic leukemia, according to a post hoc analysis of the phase 3 RESONATE trial.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

“This study ... provides further evidence for efficacy and safety with prolonged treatment across multiple high-risk genomic and clinical disease features and with increasing depth of response,” John C. Byrd, MD, of the Ohio State University, Columbus, and his colleagues wrote in Blood.

RESONATE included 391 high-risk patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Study participants were randomized in a 1:1 fashion to receive ibrutinib 420 mg daily or ofatumumab (initial infusion of 300 mg followed by seven weekly infusions and four monthly infusions of 2,000 mg) for a maximum of 24 weeks. Drug therapy was continued until cancer progression or intolerable toxicity of either agent was seen.

“Primary analysis at median follow-up of 9.7 months demonstrated superiority of ibrutinib over ofatumumab in PFS [progression-free survival], OS [overall survival], and overall response,” the researchers wrote. “With extended follow-up of median 44 months, these same results persist; a plateau of PFS has not yet been reached in this long-term follow-up. We also observe very durable remissions among patients of all genomic groups, including those with del(17)(p13.1), del(11)(q22.3), or unmutated IgHV [immunoglobulin heavy chain gene], who are traditionally considered high-risk populations.”

After an extended follow-up (median, 44 months), the team found that the PFS benefit with ibrutinib was sustained, compared with ofatumumab (hazard ratio, 0.133; 95% confidence interval, 0.099-0.178; P less than .0001). The 3-year PFS rate was 59% for ibrutinib, compared with 3% for ofatumumab. Similar PFS benefits were seen among subgroups of high- and very high–risk patients, based on their scores on the International Prognostic Index for CLL.

The OS benefit was also sustained in those randomized to ibrutinib (HR, 0.591; 95% CI, 0.378-0.926; P = .0208). The continued OS benefit with ibrutinib versus ofatumumab continued even after a sensitivity analysis adjusted for crossover of patients to ibrutinib.

With respect to safety, adverse events of any grade were similar to previous reports of ibrutinib. In fact, the prevalence of adverse events (grade 3 or higher) decreased over time for participants that continued on ibrutinib.

“Multiple studies are ongoing to investigate ibrutinib earlier in the course of CLL therapy, including phase 3 studies of first-line ibrutinib [or ibrutinib combined with anti-CD20 therapy], compared with standard chemoimmunotherapy regimens,” they wrote.

The study was sponsored by Pharmacyclics and Janssen. The authors reported financial disclosures related to the sponsors and several other companies.

SOURCE: Byrd JC et al. Blood. 2019 Mar 6. doi: 10.1182/blood-2018-08-870238.

The use of concurrent anticoagulation and emicizumab prophylaxis eliminated the need for bypassing therapy and improved a life-threatening central venous access device (CVAD)–associated thrombus in a patient with severe hemophilia A.

“Systemic anticoagulation with concomitant emicizumab has not been previously described,” Angela Weyand, MD, of the University of Michigan, Ann Arbor, and her colleagues wrote in a letter to the editor published in Haemophilia.

The researchers reported findings from a case of a 6-year-old boy with severe hemophilia A who developed a CVAD‐associated thrombus during immune tolerance induction with recombinant factor VIII (rFVIII). As his clinical condition worsened, the team hypothesized thrombus development was being caused by the ongoing use of bypassing therapy.

Dr. Weyand and her colleagues started prophylaxis with subcutaneous emicizumab (3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg weekly thereafter) and anticoagulation therapy (low-molecular-weight heparin given twice daily; anti‐Xa target of 0.3‐0.5 IU/ mL, later increased to 0.5‐0.7 IU/mL).

After 2 months of concurrent therapy, the team saw major symptomatic improvement and the thrombus had substantially decreased in size. One month later, his port access was removed without any bleeding complications and no further hemostatic agents were required.

“Follow‐up echocardiogram 3 months after discontinuation of anticoagulation demonstrated continued improvement with increasing organization of the thrombus,” they wrote.

Afterward, the patient was continued on emicizumab prophylaxis and did not require additional bypassing agent therapy.

“Consideration was given to surgical thrombectomy as that would be the recommendation in a non-haemophilic patient, but ultimately anticoagulation was deemed to be a safer alternative,” they wrote.

The researchers acknowledged that very little evidence is available to guide treatment of patients similar to the one described in this case. “Although this particular scenario is rare, its real‐life efficacy data in these types of settings will help inform emicizumab use, which is critical given its expanding indications,” they concluded.

No funding sources were reported. The authors reported financial disclosures related to Bayer, CSL Behring, Novo Nordisk, Octapharma, Shire, and others.

SOURCE: Weyand AC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13721.

The use of concurrent anticoagulation and emicizumab prophylaxis eliminated the need for bypassing therapy and improved a life-threatening central venous access device (CVAD)–associated thrombus in a patient with severe hemophilia A.

“Systemic anticoagulation with concomitant emicizumab has not been previously described,” Angela Weyand, MD, of the University of Michigan, Ann Arbor, and her colleagues wrote in a letter to the editor published in Haemophilia.

The researchers reported findings from a case of a 6-year-old boy with severe hemophilia A who developed a CVAD‐associated thrombus during immune tolerance induction with recombinant factor VIII (rFVIII). As his clinical condition worsened, the team hypothesized thrombus development was being caused by the ongoing use of bypassing therapy.

Dr. Weyand and her colleagues started prophylaxis with subcutaneous emicizumab (3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg weekly thereafter) and anticoagulation therapy (low-molecular-weight heparin given twice daily; anti‐Xa target of 0.3‐0.5 IU/ mL, later increased to 0.5‐0.7 IU/mL).

After 2 months of concurrent therapy, the team saw major symptomatic improvement and the thrombus had substantially decreased in size. One month later, his port access was removed without any bleeding complications and no further hemostatic agents were required.

“Follow‐up echocardiogram 3 months after discontinuation of anticoagulation demonstrated continued improvement with increasing organization of the thrombus,” they wrote.

Afterward, the patient was continued on emicizumab prophylaxis and did not require additional bypassing agent therapy.

“Consideration was given to surgical thrombectomy as that would be the recommendation in a non-haemophilic patient, but ultimately anticoagulation was deemed to be a safer alternative,” they wrote.

The researchers acknowledged that very little evidence is available to guide treatment of patients similar to the one described in this case. “Although this particular scenario is rare, its real‐life efficacy data in these types of settings will help inform emicizumab use, which is critical given its expanding indications,” they concluded.

No funding sources were reported. The authors reported financial disclosures related to Bayer, CSL Behring, Novo Nordisk, Octapharma, Shire, and others.

SOURCE: Weyand AC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13721.

The use of concurrent anticoagulation and emicizumab prophylaxis eliminated the need for bypassing therapy and improved a life-threatening central venous access device (CVAD)–associated thrombus in a patient with severe hemophilia A.

“Systemic anticoagulation with concomitant emicizumab has not been previously described,” Angela Weyand, MD, of the University of Michigan, Ann Arbor, and her colleagues wrote in a letter to the editor published in Haemophilia.

The researchers reported findings from a case of a 6-year-old boy with severe hemophilia A who developed a CVAD‐associated thrombus during immune tolerance induction with recombinant factor VIII (rFVIII). As his clinical condition worsened, the team hypothesized thrombus development was being caused by the ongoing use of bypassing therapy.

Dr. Weyand and her colleagues started prophylaxis with subcutaneous emicizumab (3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg weekly thereafter) and anticoagulation therapy (low-molecular-weight heparin given twice daily; anti‐Xa target of 0.3‐0.5 IU/ mL, later increased to 0.5‐0.7 IU/mL).

After 2 months of concurrent therapy, the team saw major symptomatic improvement and the thrombus had substantially decreased in size. One month later, his port access was removed without any bleeding complications and no further hemostatic agents were required.

“Follow‐up echocardiogram 3 months after discontinuation of anticoagulation demonstrated continued improvement with increasing organization of the thrombus,” they wrote.

Afterward, the patient was continued on emicizumab prophylaxis and did not require additional bypassing agent therapy.

“Consideration was given to surgical thrombectomy as that would be the recommendation in a non-haemophilic patient, but ultimately anticoagulation was deemed to be a safer alternative,” they wrote.

The researchers acknowledged that very little evidence is available to guide treatment of patients similar to the one described in this case. “Although this particular scenario is rare, its real‐life efficacy data in these types of settings will help inform emicizumab use, which is critical given its expanding indications,” they concluded.

No funding sources were reported. The authors reported financial disclosures related to Bayer, CSL Behring, Novo Nordisk, Octapharma, Shire, and others.

SOURCE: Weyand AC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13721.

For patients with primary central nervous system lymphoma (PCNSL), adding rituximab to combination high-dose methotrexate and temozolomide significantly boosted the 5-year overall survival rate, according to a retrospective study.

The triplet combination could be a safe and effective first-line option for patients with PCNSL, particularly the frail and elderly, who may have issues with toxicity when receiving current standard care, reported lead author Cui Chen, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China, and his colleagues.

“An increasing number of studies and meta‐analyses have investigated the effect of rituximab in PCNSL, indicating that rituximab can robustly enhance the response rate and possibly improve survival,” the investigators wrote in Cancer Medicine. “However, data regarding the addition of rituximab to [methotrexate and temozolomide] for PCNSL are limited, and no study has directly compared the efficacy of [rituximab/high-dose methotrexate/temozolomide] to that of [high-dose methotrexate/temozolomide].”

The study involved 62 patients with untreated PCNSL who were diagnosed between 2005 and 2015. Out of the 62 patients, 32 received rituximab/high-dose methotrexate/temozolomide (RMT) and 30 received high-dose methotrexate/temozolomide (MT). Patients received up to eight cycles of therapy, with discontinuation upon disease progression or toxicity.

The results showed that patients treated with RMT had significantly better outcomes than those who received MT, first marked by objective response rates, which were 93.7% for RMT and 69.0% for MT.

Survival rates also showed the advantage of rituximab. For the RMT group, 2-year and 5-year progression-free survival rates were 81.3% and 53.3%, respectively, compared with 46.5% and 29.1% for patients receiving MT.

Most importantly, rituximab boosted overall survival to a significant and notable extent, with higher rates at 2 years (82.3% vs. 65.7%) and 5 years (82.3% vs. 50.0%).

Efficacy did not diminish safety, as no significant differences in toxicity were found between treatment types. The most common grade 3-4 toxicities were hematologic; most commonly, this entailed neutropenia, which occurred in about one-quarter of patients.

“Given its outstanding efficacy and favorable toxicity, we consider RMT to be a feasible and safe therapeutic approach as a first‐line treatment for PCNSL. Moreover, RMT is an ideal regimen for elderly patients and frail populations who may not tolerate [whole‐brain radiation therapy] or [autologous stem‐cell transplantation],” the researchers wrote.

The study was funded by the Natural Science Foundation of Guangdong Province. The researchers reported having no conflicts of interest.

SOURCE: Chen C et al. Cancer Med. 2019 Mar 1. doi: 10.1002/cam4.1906.

For patients with primary central nervous system lymphoma (PCNSL), adding rituximab to combination high-dose methotrexate and temozolomide significantly boosted the 5-year overall survival rate, according to a retrospective study.

The triplet combination could be a safe and effective first-line option for patients with PCNSL, particularly the frail and elderly, who may have issues with toxicity when receiving current standard care, reported lead author Cui Chen, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China, and his colleagues.

“An increasing number of studies and meta‐analyses have investigated the effect of rituximab in PCNSL, indicating that rituximab can robustly enhance the response rate and possibly improve survival,” the investigators wrote in Cancer Medicine. “However, data regarding the addition of rituximab to [methotrexate and temozolomide] for PCNSL are limited, and no study has directly compared the efficacy of [rituximab/high-dose methotrexate/temozolomide] to that of [high-dose methotrexate/temozolomide].”

The study involved 62 patients with untreated PCNSL who were diagnosed between 2005 and 2015. Out of the 62 patients, 32 received rituximab/high-dose methotrexate/temozolomide (RMT) and 30 received high-dose methotrexate/temozolomide (MT). Patients received up to eight cycles of therapy, with discontinuation upon disease progression or toxicity.

The results showed that patients treated with RMT had significantly better outcomes than those who received MT, first marked by objective response rates, which were 93.7% for RMT and 69.0% for MT.

Survival rates also showed the advantage of rituximab. For the RMT group, 2-year and 5-year progression-free survival rates were 81.3% and 53.3%, respectively, compared with 46.5% and 29.1% for patients receiving MT.

Most importantly, rituximab boosted overall survival to a significant and notable extent, with higher rates at 2 years (82.3% vs. 65.7%) and 5 years (82.3% vs. 50.0%).

Efficacy did not diminish safety, as no significant differences in toxicity were found between treatment types. The most common grade 3-4 toxicities were hematologic; most commonly, this entailed neutropenia, which occurred in about one-quarter of patients.

“Given its outstanding efficacy and favorable toxicity, we consider RMT to be a feasible and safe therapeutic approach as a first‐line treatment for PCNSL. Moreover, RMT is an ideal regimen for elderly patients and frail populations who may not tolerate [whole‐brain radiation therapy] or [autologous stem‐cell transplantation],” the researchers wrote.

The study was funded by the Natural Science Foundation of Guangdong Province. The researchers reported having no conflicts of interest.

SOURCE: Chen C et al. Cancer Med. 2019 Mar 1. doi: 10.1002/cam4.1906.

For patients with primary central nervous system lymphoma (PCNSL), adding rituximab to combination high-dose methotrexate and temozolomide significantly boosted the 5-year overall survival rate, according to a retrospective study.

The triplet combination could be a safe and effective first-line option for patients with PCNSL, particularly the frail and elderly, who may have issues with toxicity when receiving current standard care, reported lead author Cui Chen, MD, of Sun Yat-Sen University Cancer Center in Guangzhou, China, and his colleagues.

“An increasing number of studies and meta‐analyses have investigated the effect of rituximab in PCNSL, indicating that rituximab can robustly enhance the response rate and possibly improve survival,” the investigators wrote in Cancer Medicine. “However, data regarding the addition of rituximab to [methotrexate and temozolomide] for PCNSL are limited, and no study has directly compared the efficacy of [rituximab/high-dose methotrexate/temozolomide] to that of [high-dose methotrexate/temozolomide].”

The study involved 62 patients with untreated PCNSL who were diagnosed between 2005 and 2015. Out of the 62 patients, 32 received rituximab/high-dose methotrexate/temozolomide (RMT) and 30 received high-dose methotrexate/temozolomide (MT). Patients received up to eight cycles of therapy, with discontinuation upon disease progression or toxicity.

The results showed that patients treated with RMT had significantly better outcomes than those who received MT, first marked by objective response rates, which were 93.7% for RMT and 69.0% for MT.

Survival rates also showed the advantage of rituximab. For the RMT group, 2-year and 5-year progression-free survival rates were 81.3% and 53.3%, respectively, compared with 46.5% and 29.1% for patients receiving MT.

Most importantly, rituximab boosted overall survival to a significant and notable extent, with higher rates at 2 years (82.3% vs. 65.7%) and 5 years (82.3% vs. 50.0%).

Efficacy did not diminish safety, as no significant differences in toxicity were found between treatment types. The most common grade 3-4 toxicities were hematologic; most commonly, this entailed neutropenia, which occurred in about one-quarter of patients.

“Given its outstanding efficacy and favorable toxicity, we consider RMT to be a feasible and safe therapeutic approach as a first‐line treatment for PCNSL. Moreover, RMT is an ideal regimen for elderly patients and frail populations who may not tolerate [whole‐brain radiation therapy] or [autologous stem‐cell transplantation],” the researchers wrote.

The study was funded by the Natural Science Foundation of Guangdong Province. The researchers reported having no conflicts of interest.

SOURCE: Chen C et al. Cancer Med. 2019 Mar 1. doi: 10.1002/cam4.1906.

The prognosis post relapse following primary radiotherapy was found to be excellent for patients with localized follicular lymphoma (FL), according to a retrospective analysis.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

But patients who experienced early relapse – at 1 year or less after diagnosis – had significantly worse survival.

While primary radiotherapy may be curative for localized FL, about 30%-50% of patients will relapse and optimal salvage therapy is not well defined, Michael S. Binkley, MD, of Stanford (Calif.) University, and his colleagues wrote in the International Journal of Radiation Oncology, Biology, Physics.

The researchers retrospectively studied 512 patients with localized FL using data from multiple centers under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Clinical information was collected, including method of detection, age at relapse, location of recurrence, and response to salvage therapy.

The team defined disease recurrence as lymphoma nonresponsive to primary radiotherapy inside of the prescribed dose volume, which included having no radiographic or clinical response within 6 months of initial radiotherapy treatment.

With a median follow-up of 52 months, Dr. Binkley and his colleagues found that 29.1% of patients developed relapsed lymphoma at a median 23 months (range, 1-143 months) following primary radiotherapy.

The team reported that the 3-year overall survival rate was 91.4% for patients with lymphoma recurrence after primary radiotherapy. In total, 16 deaths occurred during follow-up: eight were lymphoma specific deaths, three were from other causes, and in five patients the cause was unknown.

Of the 149 cases of relapsed lymphoma, 93 were indolent. There were also three cases of FL grade 3B/not otherwise specified and 18 cases of diffuse large B-cell lymphoma. In 35 patients who relapsed, biopsies were not performed.

“The excellent prognosis observed for this relapse cohort emphasizes that primary radiation for localized follicular lymphoma is an excellent treatment option,” the researchers wrote.

When the researchers examined survival based on the time of relapse, they found that overall survival was “significantly worse” for patients who had relapsed 12 months or less after the date of diagnosis, at 88.7%, compared with all others at 95.8% (P = .01).

They found no difference in overall survival between patients who received immediate salvage treatment, compared with observation after relapse (P = .28). There was also no significant difference in survival between patients who relapsed in 1 year or less but underwent immediate treatment, compared to early relapsed patients who were observed (log-rank P = .34).

“[A]ny decision to offer treatment at time of relapse must be weighed with the risk of acute and late adverse effects. Greater than 60% of patients in our cohort with indolent recurrence who underwent salvage treatment received rituximab, likely contributing to the excellent outcomes,” the researchers wrote. “However, nearly 60% of patients with indolent recurrence who were observed did not have disease progression nor [did they] receive treatment within 3 years.”

The researchers reported having no conflicts of interest.

SOURCE: Binkley MS et al. Int J Radiat Oncol Biol Phys. 2019 Mar 8. doi: 10.1016/j.ijrobp.2019.03.004.

The prognosis post relapse following primary radiotherapy was found to be excellent for patients with localized follicular lymphoma (FL), according to a retrospective analysis.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

But patients who experienced early relapse – at 1 year or less after diagnosis – had significantly worse survival.

While primary radiotherapy may be curative for localized FL, about 30%-50% of patients will relapse and optimal salvage therapy is not well defined, Michael S. Binkley, MD, of Stanford (Calif.) University, and his colleagues wrote in the International Journal of Radiation Oncology, Biology, Physics.

The researchers retrospectively studied 512 patients with localized FL using data from multiple centers under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Clinical information was collected, including method of detection, age at relapse, location of recurrence, and response to salvage therapy.

The team defined disease recurrence as lymphoma nonresponsive to primary radiotherapy inside of the prescribed dose volume, which included having no radiographic or clinical response within 6 months of initial radiotherapy treatment.

With a median follow-up of 52 months, Dr. Binkley and his colleagues found that 29.1% of patients developed relapsed lymphoma at a median 23 months (range, 1-143 months) following primary radiotherapy.

The team reported that the 3-year overall survival rate was 91.4% for patients with lymphoma recurrence after primary radiotherapy. In total, 16 deaths occurred during follow-up: eight were lymphoma specific deaths, three were from other causes, and in five patients the cause was unknown.

Of the 149 cases of relapsed lymphoma, 93 were indolent. There were also three cases of FL grade 3B/not otherwise specified and 18 cases of diffuse large B-cell lymphoma. In 35 patients who relapsed, biopsies were not performed.

“The excellent prognosis observed for this relapse cohort emphasizes that primary radiation for localized follicular lymphoma is an excellent treatment option,” the researchers wrote.

When the researchers examined survival based on the time of relapse, they found that overall survival was “significantly worse” for patients who had relapsed 12 months or less after the date of diagnosis, at 88.7%, compared with all others at 95.8% (P = .01).

They found no difference in overall survival between patients who received immediate salvage treatment, compared with observation after relapse (P = .28). There was also no significant difference in survival between patients who relapsed in 1 year or less but underwent immediate treatment, compared to early relapsed patients who were observed (log-rank P = .34).

“[A]ny decision to offer treatment at time of relapse must be weighed with the risk of acute and late adverse effects. Greater than 60% of patients in our cohort with indolent recurrence who underwent salvage treatment received rituximab, likely contributing to the excellent outcomes,” the researchers wrote. “However, nearly 60% of patients with indolent recurrence who were observed did not have disease progression nor [did they] receive treatment within 3 years.”

The researchers reported having no conflicts of interest.

SOURCE: Binkley MS et al. Int J Radiat Oncol Biol Phys. 2019 Mar 8. doi: 10.1016/j.ijrobp.2019.03.004.

The prognosis post relapse following primary radiotherapy was found to be excellent for patients with localized follicular lymphoma (FL), according to a retrospective analysis.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

But patients who experienced early relapse – at 1 year or less after diagnosis – had significantly worse survival.

While primary radiotherapy may be curative for localized FL, about 30%-50% of patients will relapse and optimal salvage therapy is not well defined, Michael S. Binkley, MD, of Stanford (Calif.) University, and his colleagues wrote in the International Journal of Radiation Oncology, Biology, Physics.

The researchers retrospectively studied 512 patients with localized FL using data from multiple centers under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Clinical information was collected, including method of detection, age at relapse, location of recurrence, and response to salvage therapy.

The team defined disease recurrence as lymphoma nonresponsive to primary radiotherapy inside of the prescribed dose volume, which included having no radiographic or clinical response within 6 months of initial radiotherapy treatment.

With a median follow-up of 52 months, Dr. Binkley and his colleagues found that 29.1% of patients developed relapsed lymphoma at a median 23 months (range, 1-143 months) following primary radiotherapy.

The team reported that the 3-year overall survival rate was 91.4% for patients with lymphoma recurrence after primary radiotherapy. In total, 16 deaths occurred during follow-up: eight were lymphoma specific deaths, three were from other causes, and in five patients the cause was unknown.

Of the 149 cases of relapsed lymphoma, 93 were indolent. There were also three cases of FL grade 3B/not otherwise specified and 18 cases of diffuse large B-cell lymphoma. In 35 patients who relapsed, biopsies were not performed.

“The excellent prognosis observed for this relapse cohort emphasizes that primary radiation for localized follicular lymphoma is an excellent treatment option,” the researchers wrote.

When the researchers examined survival based on the time of relapse, they found that overall survival was “significantly worse” for patients who had relapsed 12 months or less after the date of diagnosis, at 88.7%, compared with all others at 95.8% (P = .01).

They found no difference in overall survival between patients who received immediate salvage treatment, compared with observation after relapse (P = .28). There was also no significant difference in survival between patients who relapsed in 1 year or less but underwent immediate treatment, compared to early relapsed patients who were observed (log-rank P = .34).

“[A]ny decision to offer treatment at time of relapse must be weighed with the risk of acute and late adverse effects. Greater than 60% of patients in our cohort with indolent recurrence who underwent salvage treatment received rituximab, likely contributing to the excellent outcomes,” the researchers wrote. “However, nearly 60% of patients with indolent recurrence who were observed did not have disease progression nor [did they] receive treatment within 3 years.”

The researchers reported having no conflicts of interest.

SOURCE: Binkley MS et al. Int J Radiat Oncol Biol Phys. 2019 Mar 8. doi: 10.1016/j.ijrobp.2019.03.004.

Survival outcomes for patients with mantle cell lymphoma (MCL) substantially improved from 1995 to 2013, particularly for those with advanced-stage tumors, according to a retrospective analysis.

The median overall survival for the study period was 52 months and 57 months in two cancer databases.

“Over the past 20 years, many novel agents and treatment regimens have been developed to treat MCL,” Shuangshuang Fu, PhD, of the University of Texas, Houston, and her colleagues wrote in Cancer Epidemiology.

The researchers retrospectively studied population-based data from two separate databases: the national Surveillance, Epidemiology and End Results (SEER) database and the Texas Cancer Registry (TCR). They identified all adult patients who received a new diagnosis of MCL between Jan. 1, 1995, and Dec. 31, 2013.

A total of 9,610 patients were included in the study: 7,555 patients from SEER and 2,055 from the TCR. The team collected data related to MCL diagnosis, mortality, and other variables, including age at diagnosis, marital status, sex, and tumor stage.

In total, 76.2% and 61.6% of patients from the SEER and TCR databases, respectively, had an advanced-stage tumor.

Dr. Fu and her colleagues found that all-cause mortality rates in both groups were significantly reduced from 1995 to 2013 (SEER, P less than .001; TCR, P = .03).

In addition, the team reported that the median overall survival time for all patients in the SEER database was 52 months, and it was 57 months for the TCR database.

“MCL patients with [an] advanced stage tumor benefitted most from the introduction of newly developed regimens,” they added.

The researchers acknowledged that a key limitation of the study was the inability to assess treatment regimen–specific survival, which could only be estimated with these data.

“The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies,” they wrote.

The study was supported by grant funding from the Cancer Prevention Research Institute of Texas and the National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Fu S et al. Cancer Epidemiol. 2019 Feb;58:89-97.

Survival outcomes for patients with mantle cell lymphoma (MCL) substantially improved from 1995 to 2013, particularly for those with advanced-stage tumors, according to a retrospective analysis.

The median overall survival for the study period was 52 months and 57 months in two cancer databases.

“Over the past 20 years, many novel agents and treatment regimens have been developed to treat MCL,” Shuangshuang Fu, PhD, of the University of Texas, Houston, and her colleagues wrote in Cancer Epidemiology.

The researchers retrospectively studied population-based data from two separate databases: the national Surveillance, Epidemiology and End Results (SEER) database and the Texas Cancer Registry (TCR). They identified all adult patients who received a new diagnosis of MCL between Jan. 1, 1995, and Dec. 31, 2013.

A total of 9,610 patients were included in the study: 7,555 patients from SEER and 2,055 from the TCR. The team collected data related to MCL diagnosis, mortality, and other variables, including age at diagnosis, marital status, sex, and tumor stage.

In total, 76.2% and 61.6% of patients from the SEER and TCR databases, respectively, had an advanced-stage tumor.

Dr. Fu and her colleagues found that all-cause mortality rates in both groups were significantly reduced from 1995 to 2013 (SEER, P less than .001; TCR, P = .03).

In addition, the team reported that the median overall survival time for all patients in the SEER database was 52 months, and it was 57 months for the TCR database.

“MCL patients with [an] advanced stage tumor benefitted most from the introduction of newly developed regimens,” they added.

The researchers acknowledged that a key limitation of the study was the inability to assess treatment regimen–specific survival, which could only be estimated with these data.

“The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies,” they wrote.

The study was supported by grant funding from the Cancer Prevention Research Institute of Texas and the National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Fu S et al. Cancer Epidemiol. 2019 Feb;58:89-97.

Survival outcomes for patients with mantle cell lymphoma (MCL) substantially improved from 1995 to 2013, particularly for those with advanced-stage tumors, according to a retrospective analysis.

The median overall survival for the study period was 52 months and 57 months in two cancer databases.

“Over the past 20 years, many novel agents and treatment regimens have been developed to treat MCL,” Shuangshuang Fu, PhD, of the University of Texas, Houston, and her colleagues wrote in Cancer Epidemiology.

The researchers retrospectively studied population-based data from two separate databases: the national Surveillance, Epidemiology and End Results (SEER) database and the Texas Cancer Registry (TCR). They identified all adult patients who received a new diagnosis of MCL between Jan. 1, 1995, and Dec. 31, 2013.

A total of 9,610 patients were included in the study: 7,555 patients from SEER and 2,055 from the TCR. The team collected data related to MCL diagnosis, mortality, and other variables, including age at diagnosis, marital status, sex, and tumor stage.

In total, 76.2% and 61.6% of patients from the SEER and TCR databases, respectively, had an advanced-stage tumor.

Dr. Fu and her colleagues found that all-cause mortality rates in both groups were significantly reduced from 1995 to 2013 (SEER, P less than .001; TCR, P = .03).

In addition, the team reported that the median overall survival time for all patients in the SEER database was 52 months, and it was 57 months for the TCR database.

“MCL patients with [an] advanced stage tumor benefitted most from the introduction of newly developed regimens,” they added.

The researchers acknowledged that a key limitation of the study was the inability to assess treatment regimen–specific survival, which could only be estimated with these data.

“The findings of our study further confirmed the impact of novel agents on improved survival over time that was shown in other studies,” they wrote.

The study was supported by grant funding from the Cancer Prevention Research Institute of Texas and the National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Fu S et al. Cancer Epidemiol. 2019 Feb;58:89-97.

Doubling total body irradiation improved rates of engraftment without altering safety in patients with severe hemoglobinopathies undergoing haploidentical hematopoietic cell transplantation, new findings suggest.

Dr_Microbe/Thinkstock

“[A]lthough our previous study showed cures in most patients and low toxicity, the graft failure rate – albeit all with full host recovery – was 50%,” Francisco Javier Bolaños-Meade, MD, of Johns Hopkins University, Baltimore, and his colleagues wrote in the Lancet Haematology. The present study set out to decrease graft failure in these patients.

The researchers conducted a single-center study of 17 consecutive patients who underwent haploidentical hematopoietic cell transplantation for a severe hemoglobinopathy. A total of 12 patients had sickle cell disease and 5 had beta-thalassemia major.

Study participants received a nonmyeloablative conditioning regimen consisting of haploidentical related donors and postprocedure cyclophosphamide.

“The primary endpoint of the study was modified to evaluate engraftment by measurement of blood chimerism,” they wrote.

After analysis, Dr. Bolaños-Meade and his colleagues found that increasing total body irradiation dose from 200 cGy to 400 cGy lowered graft failure without raising toxicity. In particular, only one participant had primary graft failure, but experienced recovery of host hematopoiesis.

Of the 17 patients, 13 patients (76%) achieved full donor chimerism and 3 patients (18%) had mixed donor-host chimerism. Three patients remained on immunosuppression, the researchers reported.

With respect to safety, five patients developed acute GVHD, which varied from grade 2 to 4; chronic GVHD was seen in three patients.

“The results of our study warrant further investigation to determine whether the curative potential of allogeneic bone marrow transplantation can extend beyond the traditionally small fraction of patients with severe hemoglobinopathies who have matched donors and are healthy enough to receive myeloablative conditioning,” they wrote.

The study was funded by the National Institutes of Health and the Maryland Stem Cell Research Fund. The researchers reported financial disclosures related to Aduro Biotech, Amgen, Alexion Pharmaceuticals, Celgene, Takeda, and others.

SOURCE: Bolaños-Meade FJ et al. Lancet Haematol. 2019 Mar 13. doi: 10.1016/S2352-3026(19)30031-6.

Doubling total body irradiation improved rates of engraftment without altering safety in patients with severe hemoglobinopathies undergoing haploidentical hematopoietic cell transplantation, new findings suggest.

Dr_Microbe/Thinkstock

“[A]lthough our previous study showed cures in most patients and low toxicity, the graft failure rate – albeit all with full host recovery – was 50%,” Francisco Javier Bolaños-Meade, MD, of Johns Hopkins University, Baltimore, and his colleagues wrote in the Lancet Haematology. The present study set out to decrease graft failure in these patients.

The researchers conducted a single-center study of 17 consecutive patients who underwent haploidentical hematopoietic cell transplantation for a severe hemoglobinopathy. A total of 12 patients had sickle cell disease and 5 had beta-thalassemia major.

Study participants received a nonmyeloablative conditioning regimen consisting of haploidentical related donors and postprocedure cyclophosphamide.

“The primary endpoint of the study was modified to evaluate engraftment by measurement of blood chimerism,” they wrote.

After analysis, Dr. Bolaños-Meade and his colleagues found that increasing total body irradiation dose from 200 cGy to 400 cGy lowered graft failure without raising toxicity. In particular, only one participant had primary graft failure, but experienced recovery of host hematopoiesis.

Of the 17 patients, 13 patients (76%) achieved full donor chimerism and 3 patients (18%) had mixed donor-host chimerism. Three patients remained on immunosuppression, the researchers reported.

With respect to safety, five patients developed acute GVHD, which varied from grade 2 to 4; chronic GVHD was seen in three patients.

“The results of our study warrant further investigation to determine whether the curative potential of allogeneic bone marrow transplantation can extend beyond the traditionally small fraction of patients with severe hemoglobinopathies who have matched donors and are healthy enough to receive myeloablative conditioning,” they wrote.

The study was funded by the National Institutes of Health and the Maryland Stem Cell Research Fund. The researchers reported financial disclosures related to Aduro Biotech, Amgen, Alexion Pharmaceuticals, Celgene, Takeda, and others.

SOURCE: Bolaños-Meade FJ et al. Lancet Haematol. 2019 Mar 13. doi: 10.1016/S2352-3026(19)30031-6.

Doubling total body irradiation improved rates of engraftment without altering safety in patients with severe hemoglobinopathies undergoing haploidentical hematopoietic cell transplantation, new findings suggest.

Dr_Microbe/Thinkstock

“[A]lthough our previous study showed cures in most patients and low toxicity, the graft failure rate – albeit all with full host recovery – was 50%,” Francisco Javier Bolaños-Meade, MD, of Johns Hopkins University, Baltimore, and his colleagues wrote in the Lancet Haematology. The present study set out to decrease graft failure in these patients.

The researchers conducted a single-center study of 17 consecutive patients who underwent haploidentical hematopoietic cell transplantation for a severe hemoglobinopathy. A total of 12 patients had sickle cell disease and 5 had beta-thalassemia major.

Study participants received a nonmyeloablative conditioning regimen consisting of haploidentical related donors and postprocedure cyclophosphamide.

“The primary endpoint of the study was modified to evaluate engraftment by measurement of blood chimerism,” they wrote.

After analysis, Dr. Bolaños-Meade and his colleagues found that increasing total body irradiation dose from 200 cGy to 400 cGy lowered graft failure without raising toxicity. In particular, only one participant had primary graft failure, but experienced recovery of host hematopoiesis.

Of the 17 patients, 13 patients (76%) achieved full donor chimerism and 3 patients (18%) had mixed donor-host chimerism. Three patients remained on immunosuppression, the researchers reported.

With respect to safety, five patients developed acute GVHD, which varied from grade 2 to 4; chronic GVHD was seen in three patients.

“The results of our study warrant further investigation to determine whether the curative potential of allogeneic bone marrow transplantation can extend beyond the traditionally small fraction of patients with severe hemoglobinopathies who have matched donors and are healthy enough to receive myeloablative conditioning,” they wrote.

The study was funded by the National Institutes of Health and the Maryland Stem Cell Research Fund. The researchers reported financial disclosures related to Aduro Biotech, Amgen, Alexion Pharmaceuticals, Celgene, Takeda, and others.

SOURCE: Bolaños-Meade FJ et al. Lancet Haematol. 2019 Mar 13. doi: 10.1016/S2352-3026(19)30031-6.

Black non-Hispanic patients with mantle cell lymphoma (MCL) have a lower rate of 5-year overall survival, compared with white non-Hispanic and Hispanic patients, according to a retrospective analysis of more than 18,000 cases.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

However, black patients were also most likely to receive treatment at an academic center, which was an independent predictor of better survival, reported Nikesh N. Shah, MD, of Emory University, Atlanta, and his colleagues. This finding suggests that even academic centers still need to focus on overcoming demographic disparities.

“Racial and socioeconomic differences have been reported in many malignancies and certain lymphomas; however, few studies report on disparities in MCL,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia. “To our knowledge this is the first such study to assess racial and socioeconomic disparities in this disease.”

The investigators reviewed 18,120 patients with MCL diagnosed between 2004 and 2013; data were drawn from the National Cancer Database. The primary endpoint was overall survival from the time of diagnosis, with analyses conducted to assess various associations with race/ethnicity, facility type, clinical/tumor characteristics, cancer stage, insurance type, and other factors.

Results showed that Hispanic patients had the highest rate of overall survival, at 55.8%, followed by white patients, at 50.1%. Trailing behind these groups were black patients (46.8%) and patients of other races/ethnicities (46.0%).

Along with survival disparities, race/ethnicity was tied to certain clinical and treatment characteristics. Compared with white patients, black patients were more likely to experience B symptoms (28% vs. 25%) and have Medicaid or lack insurance (15% vs. 5%). Black and Hispanic patients were also less likely than white non-Hispanic patients to receive stem cell transplant (13% vs. 10% vs. 10%).

Although black patients were more likely than white patients to receive treatment at an academic center (51% vs. 38%), a factor independently associated with best survival among center types, whatever advantage provided apparently did not exceed disadvantages associated with race.

“We report inferior overall survival in black patients after accounting for socioeconomic status, as seen in other malignancies,” the investigators wrote. “Surprisingly, these patients were more likely to be treated at academic centers, which independently showed improved overall survival in multivariable analysis that controlled for age, disease stage, insurance status, and other socioeconomic factors.”

The researchers cited a number of steps that could help close the survival gap, including providing more comprehensive supportive care between physician visits and enrollment of patients from diverse racial background on clinical trials.

The study was funded by the National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Mar 11. doi: 10.1016/j.clml.2019.03.006.

Black non-Hispanic patients with mantle cell lymphoma (MCL) have a lower rate of 5-year overall survival, compared with white non-Hispanic and Hispanic patients, according to a retrospective analysis of more than 18,000 cases.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

However, black patients were also most likely to receive treatment at an academic center, which was an independent predictor of better survival, reported Nikesh N. Shah, MD, of Emory University, Atlanta, and his colleagues. This finding suggests that even academic centers still need to focus on overcoming demographic disparities.

“Racial and socioeconomic differences have been reported in many malignancies and certain lymphomas; however, few studies report on disparities in MCL,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia. “To our knowledge this is the first such study to assess racial and socioeconomic disparities in this disease.”

The investigators reviewed 18,120 patients with MCL diagnosed between 2004 and 2013; data were drawn from the National Cancer Database. The primary endpoint was overall survival from the time of diagnosis, with analyses conducted to assess various associations with race/ethnicity, facility type, clinical/tumor characteristics, cancer stage, insurance type, and other factors.

Results showed that Hispanic patients had the highest rate of overall survival, at 55.8%, followed by white patients, at 50.1%. Trailing behind these groups were black patients (46.8%) and patients of other races/ethnicities (46.0%).

Along with survival disparities, race/ethnicity was tied to certain clinical and treatment characteristics. Compared with white patients, black patients were more likely to experience B symptoms (28% vs. 25%) and have Medicaid or lack insurance (15% vs. 5%). Black and Hispanic patients were also less likely than white non-Hispanic patients to receive stem cell transplant (13% vs. 10% vs. 10%).

Although black patients were more likely than white patients to receive treatment at an academic center (51% vs. 38%), a factor independently associated with best survival among center types, whatever advantage provided apparently did not exceed disadvantages associated with race.

“We report inferior overall survival in black patients after accounting for socioeconomic status, as seen in other malignancies,” the investigators wrote. “Surprisingly, these patients were more likely to be treated at academic centers, which independently showed improved overall survival in multivariable analysis that controlled for age, disease stage, insurance status, and other socioeconomic factors.”

The researchers cited a number of steps that could help close the survival gap, including providing more comprehensive supportive care between physician visits and enrollment of patients from diverse racial background on clinical trials.

The study was funded by the National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Mar 11. doi: 10.1016/j.clml.2019.03.006.

Black non-Hispanic patients with mantle cell lymphoma (MCL) have a lower rate of 5-year overall survival, compared with white non-Hispanic and Hispanic patients, according to a retrospective analysis of more than 18,000 cases.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

However, black patients were also most likely to receive treatment at an academic center, which was an independent predictor of better survival, reported Nikesh N. Shah, MD, of Emory University, Atlanta, and his colleagues. This finding suggests that even academic centers still need to focus on overcoming demographic disparities.

“Racial and socioeconomic differences have been reported in many malignancies and certain lymphomas; however, few studies report on disparities in MCL,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia. “To our knowledge this is the first such study to assess racial and socioeconomic disparities in this disease.”

The investigators reviewed 18,120 patients with MCL diagnosed between 2004 and 2013; data were drawn from the National Cancer Database. The primary endpoint was overall survival from the time of diagnosis, with analyses conducted to assess various associations with race/ethnicity, facility type, clinical/tumor characteristics, cancer stage, insurance type, and other factors.

Results showed that Hispanic patients had the highest rate of overall survival, at 55.8%, followed by white patients, at 50.1%. Trailing behind these groups were black patients (46.8%) and patients of other races/ethnicities (46.0%).

Along with survival disparities, race/ethnicity was tied to certain clinical and treatment characteristics. Compared with white patients, black patients were more likely to experience B symptoms (28% vs. 25%) and have Medicaid or lack insurance (15% vs. 5%). Black and Hispanic patients were also less likely than white non-Hispanic patients to receive stem cell transplant (13% vs. 10% vs. 10%).

Although black patients were more likely than white patients to receive treatment at an academic center (51% vs. 38%), a factor independently associated with best survival among center types, whatever advantage provided apparently did not exceed disadvantages associated with race.

“We report inferior overall survival in black patients after accounting for socioeconomic status, as seen in other malignancies,” the investigators wrote. “Surprisingly, these patients were more likely to be treated at academic centers, which independently showed improved overall survival in multivariable analysis that controlled for age, disease stage, insurance status, and other socioeconomic factors.”

The researchers cited a number of steps that could help close the survival gap, including providing more comprehensive supportive care between physician visits and enrollment of patients from diverse racial background on clinical trials.

The study was funded by the National Institutes of Health. The researchers reported having no conflicts of interest.

SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Mar 11. doi: 10.1016/j.clml.2019.03.006.

High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.

Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.

For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.

Courtesy Duke Health

“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”

The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.

The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.

Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.

Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.

Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.

Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.

Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.

The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.

SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.

High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.

Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.

For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.

Courtesy Duke Health

“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”

The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.

The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.

Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.

Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.

Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.

Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.

Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.

The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.

SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.

High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.

Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.

For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.

Courtesy Duke Health

“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”

The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.

The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.

Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.

Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.

Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.

Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.

Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.

The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.

SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.

SEATTLE – HIV infection is associated with increased risk of recurrent venous thromboembolism, especially within 1 year of the initial episode. The finding, presented during a poster session at the Conference on Retroviruses & Opportunistic Infections, follows up on an earlier study that found that first-time VTE risk also is higher among HIV-positive individuals than in the general population.

Jim Kling/MDedge News

The conclusion about first-time VTE risk, published earlier this year in Lancet HIV, came from a comparison between the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort and European population-level of studies of VTE. It found a crude incidence of 2.33 VTE events per 1,000 person-years In HIV patients, with heightened odds when CD4 cell counts were below 200 cells/mcL (adjusted hazard ratio, 3.40).

The new work represents a follow-up and compared results from ATHENA (153 patients with HIV and first VTE) and the Dutch MEGA cohort (4,005 patients without HIV, with first VTE), which includes the general population. Overall, 26% of patients in the ATHENA cohort experienced a second VTE event, compared with 16% of the general population. At 1 year after anticoagulation withdrawal, HIV-positive individuals were at 67% increased risk (HR, 1.67). At 6-years after withdrawal, the relationship was not statistically significant (HR, 1.22).

Researchers also found that CD4 cell-count recovery was associated with lowered risk, with every 100 cell-count increase between initial VTE diagnosis and anticoagulant withdrawal linked to a 20% reduction in risk (HR, 0.80).

“The clinical question is: If it’s true you have an increased risk of recurrence, should you be continuing anticoagulant therapy longer in people with HIV? This poster doesn’t answer that question and you probably need a randomized, controlled trial to look at that,” Peter Reiss, MD, professor of medicine at Amsterdam University Medical Center, said in an interview during the conference.

In the absence of a clear answer, it’s sensible for clinicians to be aware of the potential increased risk, much as clinicians have internalized the increased risk of atherosclerotic vascular disease in HIV patients. “I think the publication [in Lancet HIV] as well as this poster suggest that on the venous side of things there may also be an accentuated risk,” said Dr. Reiss.

Heidi Crane, MD, a professor of medicine at the University of Washington, Seattle, presented a poster examining the underlying factors that may predispose HIV patients to first-time VTE events. Her team performed an adjudicated review of VTE cases among HIV patients at six institutions and found that the risk factors appeared to be distinct from those seen in the general population.

The traditional long plane ride was less common in this population, while factors such as injected drug use and pneumonia were more common. The VTE events occurred at a median age of 49 years; 30% of the patients had a detectable viral load. “We’re seeing a little more (VTE) than you might expect, and in a younger population than you might have guessed,” said Dr. Crane in an interview.

The most frequent predisposing risk factors were recent hospitalization (40%), infection (40%), or immobilization/bed rest (24%) within the past 90 days, and injectable drug use (22%). “It’s not just the traditional risk factors. Some HIV-specific risk factors are driving this,” said Dr. Crane.

She also aims to learn more about the specifics of risk factors, such as catheter-associated thromboses. The team is working to increase the sample size in order to parse out the relationships with specific outcomes.

In the meantime, the data further characterize the health challenges facing people living with HIV. “This is another example demonstrating that comorbid conditions among patients with HIV that are often considered age related occur at much younger ages in our population,” said Dr. Crane.

SOURCE: Rokx C et al. CROI 2019, Abstract 636; and Tenforde MW et al. CROI 2019, Abstract 637.

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SEATTLE – HIV infection is associated with increased risk of recurrent venous thromboembolism, especially within 1 year of the initial episode. The finding, presented during a poster session at the Conference on Retroviruses & Opportunistic Infections, follows up on an earlier study that found that first-time VTE risk also is higher among HIV-positive individuals than in the general population.

Jim Kling/MDedge News

The conclusion about first-time VTE risk, published earlier this year in Lancet HIV, came from a comparison between the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort and European population-level of studies of VTE. It found a crude incidence of 2.33 VTE events per 1,000 person-years In HIV patients, with heightened odds when CD4 cell counts were below 200 cells/mcL (adjusted hazard ratio, 3.40).

The new work represents a follow-up and compared results from ATHENA (153 patients with HIV and first VTE) and the Dutch MEGA cohort (4,005 patients without HIV, with first VTE), which includes the general population. Overall, 26% of patients in the ATHENA cohort experienced a second VTE event, compared with 16% of the general population. At 1 year after anticoagulation withdrawal, HIV-positive individuals were at 67% increased risk (HR, 1.67). At 6-years after withdrawal, the relationship was not statistically significant (HR, 1.22).

Researchers also found that CD4 cell-count recovery was associated with lowered risk, with every 100 cell-count increase between initial VTE diagnosis and anticoagulant withdrawal linked to a 20% reduction in risk (HR, 0.80).

“The clinical question is: If it’s true you have an increased risk of recurrence, should you be continuing anticoagulant therapy longer in people with HIV? This poster doesn’t answer that question and you probably need a randomized, controlled trial to look at that,” Peter Reiss, MD, professor of medicine at Amsterdam University Medical Center, said in an interview during the conference.

In the absence of a clear answer, it’s sensible for clinicians to be aware of the potential increased risk, much as clinicians have internalized the increased risk of atherosclerotic vascular disease in HIV patients. “I think the publication [in Lancet HIV] as well as this poster suggest that on the venous side of things there may also be an accentuated risk,” said Dr. Reiss.

Heidi Crane, MD, a professor of medicine at the University of Washington, Seattle, presented a poster examining the underlying factors that may predispose HIV patients to first-time VTE events. Her team performed an adjudicated review of VTE cases among HIV patients at six institutions and found that the risk factors appeared to be distinct from those seen in the general population.

The traditional long plane ride was less common in this population, while factors such as injected drug use and pneumonia were more common. The VTE events occurred at a median age of 49 years; 30% of the patients had a detectable viral load. “We’re seeing a little more (VTE) than you might expect, and in a younger population than you might have guessed,” said Dr. Crane in an interview.

The most frequent predisposing risk factors were recent hospitalization (40%), infection (40%), or immobilization/bed rest (24%) within the past 90 days, and injectable drug use (22%). “It’s not just the traditional risk factors. Some HIV-specific risk factors are driving this,” said Dr. Crane.

She also aims to learn more about the specifics of risk factors, such as catheter-associated thromboses. The team is working to increase the sample size in order to parse out the relationships with specific outcomes.

In the meantime, the data further characterize the health challenges facing people living with HIV. “This is another example demonstrating that comorbid conditions among patients with HIV that are often considered age related occur at much younger ages in our population,” said Dr. Crane.

SOURCE: Rokx C et al. CROI 2019, Abstract 636; and Tenforde MW et al. CROI 2019, Abstract 637.

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SEATTLE – HIV infection is associated with increased risk of recurrent venous thromboembolism, especially within 1 year of the initial episode. The finding, presented during a poster session at the Conference on Retroviruses & Opportunistic Infections, follows up on an earlier study that found that first-time VTE risk also is higher among HIV-positive individuals than in the general population.

Jim Kling/MDedge News

The conclusion about first-time VTE risk, published earlier this year in Lancet HIV, came from a comparison between the ATHENA (AIDS Therapy Evaluation in the Netherlands) cohort and European population-level of studies of VTE. It found a crude incidence of 2.33 VTE events per 1,000 person-years In HIV patients, with heightened odds when CD4 cell counts were below 200 cells/mcL (adjusted hazard ratio, 3.40).

The new work represents a follow-up and compared results from ATHENA (153 patients with HIV and first VTE) and the Dutch MEGA cohort (4,005 patients without HIV, with first VTE), which includes the general population. Overall, 26% of patients in the ATHENA cohort experienced a second VTE event, compared with 16% of the general population. At 1 year after anticoagulation withdrawal, HIV-positive individuals were at 67% increased risk (HR, 1.67). At 6-years after withdrawal, the relationship was not statistically significant (HR, 1.22).

Researchers also found that CD4 cell-count recovery was associated with lowered risk, with every 100 cell-count increase between initial VTE diagnosis and anticoagulant withdrawal linked to a 20% reduction in risk (HR, 0.80).

“The clinical question is: If it’s true you have an increased risk of recurrence, should you be continuing anticoagulant therapy longer in people with HIV? This poster doesn’t answer that question and you probably need a randomized, controlled trial to look at that,” Peter Reiss, MD, professor of medicine at Amsterdam University Medical Center, said in an interview during the conference.

In the absence of a clear answer, it’s sensible for clinicians to be aware of the potential increased risk, much as clinicians have internalized the increased risk of atherosclerotic vascular disease in HIV patients. “I think the publication [in Lancet HIV] as well as this poster suggest that on the venous side of things there may also be an accentuated risk,” said Dr. Reiss.

Heidi Crane, MD, a professor of medicine at the University of Washington, Seattle, presented a poster examining the underlying factors that may predispose HIV patients to first-time VTE events. Her team performed an adjudicated review of VTE cases among HIV patients at six institutions and found that the risk factors appeared to be distinct from those seen in the general population.

The traditional long plane ride was less common in this population, while factors such as injected drug use and pneumonia were more common. The VTE events occurred at a median age of 49 years; 30% of the patients had a detectable viral load. “We’re seeing a little more (VTE) than you might expect, and in a younger population than you might have guessed,” said Dr. Crane in an interview.

The most frequent predisposing risk factors were recent hospitalization (40%), infection (40%), or immobilization/bed rest (24%) within the past 90 days, and injectable drug use (22%). “It’s not just the traditional risk factors. Some HIV-specific risk factors are driving this,” said Dr. Crane.

She also aims to learn more about the specifics of risk factors, such as catheter-associated thromboses. The team is working to increase the sample size in order to parse out the relationships with specific outcomes.

In the meantime, the data further characterize the health challenges facing people living with HIV. “This is another example demonstrating that comorbid conditions among patients with HIV that are often considered age related occur at much younger ages in our population,” said Dr. Crane.

SOURCE: Rokx C et al. CROI 2019, Abstract 636; and Tenforde MW et al. CROI 2019, Abstract 637.

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