Hematology Times

Photo courtesy of Celgene

Lenalidomide may be the best maintenance treatment option for patients with newly diagnosed multiple myeloma (MM), according to the authors of a systematic review and meta-analysis.

Francesca M. Gay, MD, PhD, of the University of Torino in Italy, and her coauthors wrote that, despite the well-recognized importance of novel agent–based maintenance therapy for MM, there is a lack of direct or indirect comparisons between the available regimens.

In a paper published in JAMA Oncology, the researchers reported the results of a systematic review and meta-analysis of 11 prospective, phase 3, randomized, controlled trials of 8 varieties of maintenance therapy in 5073 participants with newly diagnosed MM.

The researchers found that lenalidomide-based regimens showed the best progression-free survival rates, compared with placebo. The hazard ratio (HR) was 0.39 for lenalidomide plus prednisone, and the HR was 0.47 for lenalidomide alone.

In 74% of the network meta-analysis simulations, lenalidomide-based regimens were the most effective options.

Four other maintenance treatment options—thalidomide-interferon (HR, 0.50), thalidomide-bortezomib (HR, 0.58), bortezomib-prednisone (HR, 0.72), and thalidomide alone (HR, 0.73)—also showed progression-free survival gains, but interferon therapy (HR, 0.91) failed to show any benefit.

For overall survival, lenalidomide alone (HR, 0.76) was the best option, followed by thalidomide-bortezomib (HR, 0.82) and bortezomib-prednisone (HR, 0.84). None of the other regimens considered showed benefits for overall survival.

“Long-term use of lenalidomide undoubtedly has advantages, owing to the lack of neuropathy, which is the main factor limiting the long-term use of both thalidomide and bortezomib,” the authors wrote.

When the authors restricted their analysis to trials conducted in the setting of autologous stem cell transplant, they found similar results, with lenalidomide-based regimens having the best progression-free and overall survival.

Patients with a good prognosis and standard-risk chromosomal abnormalities also did best with lenalidomide-based maintenance, while those with a poor prognosis—for example, with ISS stage III disease—benefited more from bortezomib-based maintenance.

However, patients with high-risk chromosomal abnormalities gained no advantage from any regimen, which the authors suggested may relate to small sample size, different cut-off points, or the patients’ extremely poor prognosis.

The authors noted that their analysis did not take into account adverse events, drug discontinuations, or quality of life but focused solely on progression-free survival and overall survival.

“An increase in second primary malignant disease with prolonged lenalidomide therapy has been reported, but the survival benefit overcame the risk in all the trials,” they wrote.

The authors also commented that better treatment options are needed for patients with aggressive disease, and there are ongoing trials looking at second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for maintenance therapy.

Most authors declared research funding, advisory board positions, fees, and honoraria from the pharmaceutical industry, including lenalidomide manufacturer Celgene.

Photo courtesy of Celgene

Lenalidomide may be the best maintenance treatment option for patients with newly diagnosed multiple myeloma (MM), according to the authors of a systematic review and meta-analysis.

Francesca M. Gay, MD, PhD, of the University of Torino in Italy, and her coauthors wrote that, despite the well-recognized importance of novel agent–based maintenance therapy for MM, there is a lack of direct or indirect comparisons between the available regimens.

In a paper published in JAMA Oncology, the researchers reported the results of a systematic review and meta-analysis of 11 prospective, phase 3, randomized, controlled trials of 8 varieties of maintenance therapy in 5073 participants with newly diagnosed MM.

The researchers found that lenalidomide-based regimens showed the best progression-free survival rates, compared with placebo. The hazard ratio (HR) was 0.39 for lenalidomide plus prednisone, and the HR was 0.47 for lenalidomide alone.

In 74% of the network meta-analysis simulations, lenalidomide-based regimens were the most effective options.

Four other maintenance treatment options—thalidomide-interferon (HR, 0.50), thalidomide-bortezomib (HR, 0.58), bortezomib-prednisone (HR, 0.72), and thalidomide alone (HR, 0.73)—also showed progression-free survival gains, but interferon therapy (HR, 0.91) failed to show any benefit.

For overall survival, lenalidomide alone (HR, 0.76) was the best option, followed by thalidomide-bortezomib (HR, 0.82) and bortezomib-prednisone (HR, 0.84). None of the other regimens considered showed benefits for overall survival.

“Long-term use of lenalidomide undoubtedly has advantages, owing to the lack of neuropathy, which is the main factor limiting the long-term use of both thalidomide and bortezomib,” the authors wrote.

When the authors restricted their analysis to trials conducted in the setting of autologous stem cell transplant, they found similar results, with lenalidomide-based regimens having the best progression-free and overall survival.

Patients with a good prognosis and standard-risk chromosomal abnormalities also did best with lenalidomide-based maintenance, while those with a poor prognosis—for example, with ISS stage III disease—benefited more from bortezomib-based maintenance.

However, patients with high-risk chromosomal abnormalities gained no advantage from any regimen, which the authors suggested may relate to small sample size, different cut-off points, or the patients’ extremely poor prognosis.

The authors noted that their analysis did not take into account adverse events, drug discontinuations, or quality of life but focused solely on progression-free survival and overall survival.

“An increase in second primary malignant disease with prolonged lenalidomide therapy has been reported, but the survival benefit overcame the risk in all the trials,” they wrote.

The authors also commented that better treatment options are needed for patients with aggressive disease, and there are ongoing trials looking at second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for maintenance therapy.

Most authors declared research funding, advisory board positions, fees, and honoraria from the pharmaceutical industry, including lenalidomide manufacturer Celgene.

Photo courtesy of Celgene

Lenalidomide may be the best maintenance treatment option for patients with newly diagnosed multiple myeloma (MM), according to the authors of a systematic review and meta-analysis.

Francesca M. Gay, MD, PhD, of the University of Torino in Italy, and her coauthors wrote that, despite the well-recognized importance of novel agent–based maintenance therapy for MM, there is a lack of direct or indirect comparisons between the available regimens.

In a paper published in JAMA Oncology, the researchers reported the results of a systematic review and meta-analysis of 11 prospective, phase 3, randomized, controlled trials of 8 varieties of maintenance therapy in 5073 participants with newly diagnosed MM.

The researchers found that lenalidomide-based regimens showed the best progression-free survival rates, compared with placebo. The hazard ratio (HR) was 0.39 for lenalidomide plus prednisone, and the HR was 0.47 for lenalidomide alone.

In 74% of the network meta-analysis simulations, lenalidomide-based regimens were the most effective options.

Four other maintenance treatment options—thalidomide-interferon (HR, 0.50), thalidomide-bortezomib (HR, 0.58), bortezomib-prednisone (HR, 0.72), and thalidomide alone (HR, 0.73)—also showed progression-free survival gains, but interferon therapy (HR, 0.91) failed to show any benefit.

For overall survival, lenalidomide alone (HR, 0.76) was the best option, followed by thalidomide-bortezomib (HR, 0.82) and bortezomib-prednisone (HR, 0.84). None of the other regimens considered showed benefits for overall survival.

“Long-term use of lenalidomide undoubtedly has advantages, owing to the lack of neuropathy, which is the main factor limiting the long-term use of both thalidomide and bortezomib,” the authors wrote.

When the authors restricted their analysis to trials conducted in the setting of autologous stem cell transplant, they found similar results, with lenalidomide-based regimens having the best progression-free and overall survival.

Patients with a good prognosis and standard-risk chromosomal abnormalities also did best with lenalidomide-based maintenance, while those with a poor prognosis—for example, with ISS stage III disease—benefited more from bortezomib-based maintenance.

However, patients with high-risk chromosomal abnormalities gained no advantage from any regimen, which the authors suggested may relate to small sample size, different cut-off points, or the patients’ extremely poor prognosis.

The authors noted that their analysis did not take into account adverse events, drug discontinuations, or quality of life but focused solely on progression-free survival and overall survival.

“An increase in second primary malignant disease with prolonged lenalidomide therapy has been reported, but the survival benefit overcame the risk in all the trials,” they wrote.

The authors also commented that better treatment options are needed for patients with aggressive disease, and there are ongoing trials looking at second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for maintenance therapy.

Most authors declared research funding, advisory board positions, fees, and honoraria from the pharmaceutical industry, including lenalidomide manufacturer Celgene.

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo by Juan D. Alfonso

Researchers say they have determined which blood tests can help general practitioners (GPs) rule out a diagnosis of multiple myeloma (MM).

The team discovered that plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) were more helpful in ruling out MM than a C-reactive protein (CRP) test.

Furthermore, the possibility of MM “is extremely low” in patients with normal hemoglobin (Hb) and normal PV or ESR.

“Ordinarily, a GP will see a patient with myeloma every 5 years, and early diagnosis matters,” said study author William Hamilton, MD, of the University of Exeter Medical School in the UK.

“We report a simple way a GP can check patients presenting symptoms such as back, rib, and chest pain or recurrent chest infections and determine whether they have myeloma or not.”

Dr Hamilton and his colleagues reported their findings in the British Journal of General Practice.

The researchers analyzed blood tests performed on 2703 MM patients up to 5 years prior to diagnosis. The team then compared results in the MM cases to blood test results in 12,157 patients without MM, matched for age and other relevant parameters.

The researchers used likelihood ratios (LRs) to classify tests as useful for ruling in or ruling out MM.

The team explained that positive likelihood (LR+) tests indicate how many times more likely a positive test occurs in individuals with MM than in those without the disease. Negative likelihood (LR–) tests indicate how many times less likely a negative result will occur in individuals with MM than in those without MM.

A test was defined as useful for ruling in MM if the LR+ was ≥ 5 and useful for ruling out MM if the LR– was ≤ 0.2.

Results

None of the inflammatory markers analyzed proved useful (LR+ ≥ 5) for ruling in MM.

The LR+ was:

• 2.0 for raised PV
• 1.9 for raised ESR
• 1.2 for raised CRP.

Similarly, none of the tests alone was useful (LR– ≤ 0.2) for ruling out MM.

The LR– was:

• 0.42 for normal Hb
• 0.81 for normal calcium
• 0.80 for normal creatinine
• 0.28 for normal ESR
• 0.32 for normal PV
• 0.87 for normal CRP.

However, several combinations of tests were useful for ruling out MM.

Conclusions/implications

The researchers concluded that, with normal Hb and normal PV or ESR, the possibility of MM is very low, and assessing CRP or creatinine as well increases the sensitivity of testing only slightly.

“The combination of levels of hemoglobin . . . and 1 of 2 inflammatory markers [ESR or PV] are a sufficient test rule out myeloma,” said study author Constantinos Koshiaris, of the University of Oxford in the UK.

“If abnormalities are detected in this test, it should lead to urgent urine protein tests, which can help speed up diagnosis.”

The researchers also recommend adding calcium tests if patients have certain symptoms, such as back pain, rib pain, joint pain, and fracture.

Photo by Juan D. Alfonso

Researchers say they have determined which blood tests can help general practitioners (GPs) rule out a diagnosis of multiple myeloma (MM).

The team discovered that plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) were more helpful in ruling out MM than a C-reactive protein (CRP) test.

Furthermore, the possibility of MM “is extremely low” in patients with normal hemoglobin (Hb) and normal PV or ESR.

“Ordinarily, a GP will see a patient with myeloma every 5 years, and early diagnosis matters,” said study author William Hamilton, MD, of the University of Exeter Medical School in the UK.

“We report a simple way a GP can check patients presenting symptoms such as back, rib, and chest pain or recurrent chest infections and determine whether they have myeloma or not.”

Dr Hamilton and his colleagues reported their findings in the British Journal of General Practice.

The researchers analyzed blood tests performed on 2703 MM patients up to 5 years prior to diagnosis. The team then compared results in the MM cases to blood test results in 12,157 patients without MM, matched for age and other relevant parameters.

The researchers used likelihood ratios (LRs) to classify tests as useful for ruling in or ruling out MM.

The team explained that positive likelihood (LR+) tests indicate how many times more likely a positive test occurs in individuals with MM than in those without the disease. Negative likelihood (LR–) tests indicate how many times less likely a negative result will occur in individuals with MM than in those without MM.

A test was defined as useful for ruling in MM if the LR+ was ≥ 5 and useful for ruling out MM if the LR– was ≤ 0.2.

Results

None of the inflammatory markers analyzed proved useful (LR+ ≥ 5) for ruling in MM.

The LR+ was:

• 2.0 for raised PV
• 1.9 for raised ESR
• 1.2 for raised CRP.

Similarly, none of the tests alone was useful (LR– ≤ 0.2) for ruling out MM.

The LR– was:

• 0.42 for normal Hb
• 0.81 for normal calcium
• 0.80 for normal creatinine
• 0.28 for normal ESR
• 0.32 for normal PV
• 0.87 for normal CRP.

However, several combinations of tests were useful for ruling out MM.

Conclusions/implications

The researchers concluded that, with normal Hb and normal PV or ESR, the possibility of MM is very low, and assessing CRP or creatinine as well increases the sensitivity of testing only slightly.

“The combination of levels of hemoglobin . . . and 1 of 2 inflammatory markers [ESR or PV] are a sufficient test rule out myeloma,” said study author Constantinos Koshiaris, of the University of Oxford in the UK.

“If abnormalities are detected in this test, it should lead to urgent urine protein tests, which can help speed up diagnosis.”

The researchers also recommend adding calcium tests if patients have certain symptoms, such as back pain, rib pain, joint pain, and fracture.

Photo by Juan D. Alfonso

Researchers say they have determined which blood tests can help general practitioners (GPs) rule out a diagnosis of multiple myeloma (MM).

The team discovered that plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) were more helpful in ruling out MM than a C-reactive protein (CRP) test.

Furthermore, the possibility of MM “is extremely low” in patients with normal hemoglobin (Hb) and normal PV or ESR.

“Ordinarily, a GP will see a patient with myeloma every 5 years, and early diagnosis matters,” said study author William Hamilton, MD, of the University of Exeter Medical School in the UK.

“We report a simple way a GP can check patients presenting symptoms such as back, rib, and chest pain or recurrent chest infections and determine whether they have myeloma or not.”

Dr Hamilton and his colleagues reported their findings in the British Journal of General Practice.

The researchers analyzed blood tests performed on 2703 MM patients up to 5 years prior to diagnosis. The team then compared results in the MM cases to blood test results in 12,157 patients without MM, matched for age and other relevant parameters.

The researchers used likelihood ratios (LRs) to classify tests as useful for ruling in or ruling out MM.

The team explained that positive likelihood (LR+) tests indicate how many times more likely a positive test occurs in individuals with MM than in those without the disease. Negative likelihood (LR–) tests indicate how many times less likely a negative result will occur in individuals with MM than in those without MM.

A test was defined as useful for ruling in MM if the LR+ was ≥ 5 and useful for ruling out MM if the LR– was ≤ 0.2.

Results

None of the inflammatory markers analyzed proved useful (LR+ ≥ 5) for ruling in MM.

The LR+ was:

• 2.0 for raised PV
• 1.9 for raised ESR
• 1.2 for raised CRP.

Similarly, none of the tests alone was useful (LR– ≤ 0.2) for ruling out MM.

The LR– was:

• 0.42 for normal Hb
• 0.81 for normal calcium
• 0.80 for normal creatinine
• 0.28 for normal ESR
• 0.32 for normal PV
• 0.87 for normal CRP.

However, several combinations of tests were useful for ruling out MM.

Conclusions/implications

The researchers concluded that, with normal Hb and normal PV or ESR, the possibility of MM is very low, and assessing CRP or creatinine as well increases the sensitivity of testing only slightly.

“The combination of levels of hemoglobin . . . and 1 of 2 inflammatory markers [ESR or PV] are a sufficient test rule out myeloma,” said study author Constantinos Koshiaris, of the University of Oxford in the UK.

“If abnormalities are detected in this test, it should lead to urgent urine protein tests, which can help speed up diagnosis.”

The researchers also recommend adding calcium tests if patients have certain symptoms, such as back pain, rib pain, joint pain, and fracture.

Photo by Rhoda Baer

Better communication between cancer patients and healthcare providers may provide tangible benefits, according to research published in JNCCN.

Cancer survivors who reported greater satisfaction in communicating with healthcare providers had better general health and mental health, fewer doctor visits, and reduced healthcare spending, when compared to patients who were less satisfied with communication.

“Our study suggests that when cancer care providers are more effective communicators, their patients are more likely to follow medical advice and medication protocols,” said study author Ashish Rai, PhD, of the American Cancer Society in Framingham, Massachusetts.

For this study, Dr Rai and his colleagues analyzed data from the Medical Expenditure Panel Survey (MEPS) from 2008 through 2014.

The researchers evaluated 4588 cancer survivors, dividing them into non-elderly and elderly groups. The non-elderly patients (n=2257) had a median age of 54 (range, 18-64), and the elderly patients (n=2331) had a median age of 75.

Communication satisfaction was measured by the Consumer Assessment of Healthcare Providers and Systems (CAHPS), in conjunction with the MEPS data.

Patients used a 4-point scale ranging from “never” to “always” to track whether their providers did the following:

• Listened carefully
• Explained things in a way that was easy to understand
• Showed respect for what the respondent had to say
• Spent enough time with the respondent.

A global satisfaction rating scale (0 to 10) was factored into a composite score and tracked across 12 months.

The researchers then assessed various patient outcomes.

Satisfaction and outcomes

Overall, patients who were the most satisfied with communication had the best outcomes with regard to general, physical, and mental health; fewer emergency department, hospital, and office visits; and reduced drug, out-of-pocket, and total healthcare expenditures.

However, the associations between communication satisfaction and outcomes were not always significant.

In an adjusted analysis, the elderly patients who were more satisfied with communication in year 1 had significantly better outcomes in year 2 for general health, mental health, and total healthcare expenditures.

For the non-elderly patients, those who were more satisfied with communication in year 1 had significantly better outcomes in year 2 for physician office visits and mental health.

Baseline health and satisfaction

In both age groups, patients with better baseline health reported higher satisfaction with communication. Conversely, the more comorbidities patients had, the lower their satisfaction rating.

The researchers said this suggests that more complex circumstances negatively impacted patients’ perception of their communication, and the finding highlights the importance of coordinating care across a team of providers.

“The results of this study present an interesting challenge: those survivors most in need of good communication about complex medical issues may not be receiving the information they seek in a manner that they find helpful. That, in turn, results in higher healthcare utilization and expenditure,” said Crystal Denlinger, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in this study.

“This could be due to many factors, including time constraints, competing priorities, and increasingly complex cancer therapies. This study highlights the need for additional research into how to tailor the healthcare experience both during and after cancer treatment in order to communicate more effectively.”

Conclusions

“Communication needs vary from patient to patient,” Dr Rai noted. “While time constraints do pose a challenge, the amount of time spent is only one of the attributes of effective communication. By tailoring their communication strategy to a patient’s specific needs, providers may be able to communicate more effectively in the same amount of time.”

Dr Rai also pointed out the importance of delegating both clinical and communication duties as needed. Dr Rai and his colleagues also cited earlier research demonstrating better outcomes for patients who had the option of communicating with their provider electronically.^1,2

Ultimately, the researchers concluded that effective provider communication can improve outcomes by streamlining care, alleviating anxiety, boosting mutual trust, and increasing treatment adherence.

1. Basch E, Deal AM, Dueck AC, et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017;318:197–198.

2. Smith AB, Basch E. Role of patient-reported outcomes in postsurgical monitoring in oncology. J Oncol Pract 2017;13:535–538.

Photo by Rhoda Baer

Better communication between cancer patients and healthcare providers may provide tangible benefits, according to research published in JNCCN.

Cancer survivors who reported greater satisfaction in communicating with healthcare providers had better general health and mental health, fewer doctor visits, and reduced healthcare spending, when compared to patients who were less satisfied with communication.

“Our study suggests that when cancer care providers are more effective communicators, their patients are more likely to follow medical advice and medication protocols,” said study author Ashish Rai, PhD, of the American Cancer Society in Framingham, Massachusetts.

For this study, Dr Rai and his colleagues analyzed data from the Medical Expenditure Panel Survey (MEPS) from 2008 through 2014.

The researchers evaluated 4588 cancer survivors, dividing them into non-elderly and elderly groups. The non-elderly patients (n=2257) had a median age of 54 (range, 18-64), and the elderly patients (n=2331) had a median age of 75.

Communication satisfaction was measured by the Consumer Assessment of Healthcare Providers and Systems (CAHPS), in conjunction with the MEPS data.

Patients used a 4-point scale ranging from “never” to “always” to track whether their providers did the following:

• Listened carefully
• Explained things in a way that was easy to understand
• Showed respect for what the respondent had to say
• Spent enough time with the respondent.

A global satisfaction rating scale (0 to 10) was factored into a composite score and tracked across 12 months.

The researchers then assessed various patient outcomes.

Satisfaction and outcomes

Overall, patients who were the most satisfied with communication had the best outcomes with regard to general, physical, and mental health; fewer emergency department, hospital, and office visits; and reduced drug, out-of-pocket, and total healthcare expenditures.

However, the associations between communication satisfaction and outcomes were not always significant.

In an adjusted analysis, the elderly patients who were more satisfied with communication in year 1 had significantly better outcomes in year 2 for general health, mental health, and total healthcare expenditures.

For the non-elderly patients, those who were more satisfied with communication in year 1 had significantly better outcomes in year 2 for physician office visits and mental health.

Baseline health and satisfaction

In both age groups, patients with better baseline health reported higher satisfaction with communication. Conversely, the more comorbidities patients had, the lower their satisfaction rating.

The researchers said this suggests that more complex circumstances negatively impacted patients’ perception of their communication, and the finding highlights the importance of coordinating care across a team of providers.

“The results of this study present an interesting challenge: those survivors most in need of good communication about complex medical issues may not be receiving the information they seek in a manner that they find helpful. That, in turn, results in higher healthcare utilization and expenditure,” said Crystal Denlinger, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in this study.

“This could be due to many factors, including time constraints, competing priorities, and increasingly complex cancer therapies. This study highlights the need for additional research into how to tailor the healthcare experience both during and after cancer treatment in order to communicate more effectively.”

Conclusions

“Communication needs vary from patient to patient,” Dr Rai noted. “While time constraints do pose a challenge, the amount of time spent is only one of the attributes of effective communication. By tailoring their communication strategy to a patient’s specific needs, providers may be able to communicate more effectively in the same amount of time.”

Dr Rai also pointed out the importance of delegating both clinical and communication duties as needed. Dr Rai and his colleagues also cited earlier research demonstrating better outcomes for patients who had the option of communicating with their provider electronically.^1,2

Ultimately, the researchers concluded that effective provider communication can improve outcomes by streamlining care, alleviating anxiety, boosting mutual trust, and increasing treatment adherence.

1. Basch E, Deal AM, Dueck AC, et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017;318:197–198.

2. Smith AB, Basch E. Role of patient-reported outcomes in postsurgical monitoring in oncology. J Oncol Pract 2017;13:535–538.

Photo by Rhoda Baer

Better communication between cancer patients and healthcare providers may provide tangible benefits, according to research published in JNCCN.

Cancer survivors who reported greater satisfaction in communicating with healthcare providers had better general health and mental health, fewer doctor visits, and reduced healthcare spending, when compared to patients who were less satisfied with communication.

“Our study suggests that when cancer care providers are more effective communicators, their patients are more likely to follow medical advice and medication protocols,” said study author Ashish Rai, PhD, of the American Cancer Society in Framingham, Massachusetts.

For this study, Dr Rai and his colleagues analyzed data from the Medical Expenditure Panel Survey (MEPS) from 2008 through 2014.

The researchers evaluated 4588 cancer survivors, dividing them into non-elderly and elderly groups. The non-elderly patients (n=2257) had a median age of 54 (range, 18-64), and the elderly patients (n=2331) had a median age of 75.

Communication satisfaction was measured by the Consumer Assessment of Healthcare Providers and Systems (CAHPS), in conjunction with the MEPS data.

Patients used a 4-point scale ranging from “never” to “always” to track whether their providers did the following:

• Listened carefully
• Explained things in a way that was easy to understand
• Showed respect for what the respondent had to say
• Spent enough time with the respondent.

A global satisfaction rating scale (0 to 10) was factored into a composite score and tracked across 12 months.

The researchers then assessed various patient outcomes.

Satisfaction and outcomes

Overall, patients who were the most satisfied with communication had the best outcomes with regard to general, physical, and mental health; fewer emergency department, hospital, and office visits; and reduced drug, out-of-pocket, and total healthcare expenditures.

However, the associations between communication satisfaction and outcomes were not always significant.

In an adjusted analysis, the elderly patients who were more satisfied with communication in year 1 had significantly better outcomes in year 2 for general health, mental health, and total healthcare expenditures.

For the non-elderly patients, those who were more satisfied with communication in year 1 had significantly better outcomes in year 2 for physician office visits and mental health.

Baseline health and satisfaction

In both age groups, patients with better baseline health reported higher satisfaction with communication. Conversely, the more comorbidities patients had, the lower their satisfaction rating.

The researchers said this suggests that more complex circumstances negatively impacted patients’ perception of their communication, and the finding highlights the importance of coordinating care across a team of providers.

“The results of this study present an interesting challenge: those survivors most in need of good communication about complex medical issues may not be receiving the information they seek in a manner that they find helpful. That, in turn, results in higher healthcare utilization and expenditure,” said Crystal Denlinger, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in this study.

“This could be due to many factors, including time constraints, competing priorities, and increasingly complex cancer therapies. This study highlights the need for additional research into how to tailor the healthcare experience both during and after cancer treatment in order to communicate more effectively.”

Conclusions

“Communication needs vary from patient to patient,” Dr Rai noted. “While time constraints do pose a challenge, the amount of time spent is only one of the attributes of effective communication. By tailoring their communication strategy to a patient’s specific needs, providers may be able to communicate more effectively in the same amount of time.”

Dr Rai also pointed out the importance of delegating both clinical and communication duties as needed. Dr Rai and his colleagues also cited earlier research demonstrating better outcomes for patients who had the option of communicating with their provider electronically.^1,2

Ultimately, the researchers concluded that effective provider communication can improve outcomes by streamlining care, alleviating anxiety, boosting mutual trust, and increasing treatment adherence.

1. Basch E, Deal AM, Dueck AC, et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017;318:197–198.

2. Smith AB, Basch E. Role of patient-reported outcomes in postsurgical monitoring in oncology. J Oncol Pract 2017;13:535–538.

Photo by Bill Branson

The US Food and Drug Administration(FDA) has accepted for priority review the biologics license application seeking approval for tagraxofusp (Elzonris, SL-401) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The FDA expects to make a decision on this application by February 21, 2019.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

About tagraxofusp

Tagraxofusp is a targeted therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. The drug is being developed by Stemline Therapeutics, Inc.

In addition to priority review, tagraxofusp has breakthrough therapy designation and orphan drug designation from the FDA.

Tagraxofusp has produced favorable early results in a phase 2 trial of patients with BPDCN. Results from this trial were presented at the 23rd Congress of the European Hematology Association (EHA) in June.

Results were presented for 45 patients—32 with previously untreated BPDCN and 13 with relapsed/refractory BPDCN.

Three patients received tagraxofusp at 7 μg/kg/day on days 1 to 5 of a 21-day cycle, and the rest received the drug at 12 μg/kg on days 1 to 5 of a 21-day cycle.

Among patients who received the 12 μg/kg/day dose, the overall response rate was 83% (35/42). The overall response rate was 90% (26/29) in the previously untreated patients and 69% (9/13) in relapsed/refractory patients.

The composite complete response rate was 62% (n=26) overall, 72% (n=21) in previously untreated patients, and 38% (n=5) in relapsed/refractory patients.

Fourteen patients went on to stem cell transplant, 1 of whom had relapsed/refractory disease at baseline.

Overall survival results were only available for the 29 previously untreated patients who received tagraxofusp at 12 μg/kg/day. In this group, the median overall survival had not been reached at a median follow-up of 13.8 months (range, 0.2 to 37.4 months).

Safety results were presented for 114 patients who have received tagraxofusp at 12 μg/kg/day on all trials of the drug. These data include patients with diseases other than BPDCN, although adverse events (AEs) were similar regardless of disease.

Common treatment-related AEs (of any grade, occurring in at least 15% of patients) included hypoalbuminemia (49%), ALT increase (48%), AST increase (48%), thrombocytopenia (29%), nausea (27%), pyrexia (25%), chills (23%), fatigue (23%), weight increase (19%), hypotension (18%), peripheral edema (17%), and vomiting (15%).

Another common AE was capillary leak syndrome (CLS), which occurred in 20% of patients (n=23). Most cases of CLS were grade 1 or 2, but there were grade 3 (n=5) and 4 (n=2) cases, as well as a single case of grade 5 CLS that occurred in a BPDCN patient.

Researchers found they could manage the CLS with monitoring and protocol adjustments.

Photo by Bill Branson

The US Food and Drug Administration(FDA) has accepted for priority review the biologics license application seeking approval for tagraxofusp (Elzonris, SL-401) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The FDA expects to make a decision on this application by February 21, 2019.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

About tagraxofusp

Tagraxofusp is a targeted therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. The drug is being developed by Stemline Therapeutics, Inc.

In addition to priority review, tagraxofusp has breakthrough therapy designation and orphan drug designation from the FDA.

Tagraxofusp has produced favorable early results in a phase 2 trial of patients with BPDCN. Results from this trial were presented at the 23rd Congress of the European Hematology Association (EHA) in June.

Results were presented for 45 patients—32 with previously untreated BPDCN and 13 with relapsed/refractory BPDCN.

Three patients received tagraxofusp at 7 μg/kg/day on days 1 to 5 of a 21-day cycle, and the rest received the drug at 12 μg/kg on days 1 to 5 of a 21-day cycle.

Among patients who received the 12 μg/kg/day dose, the overall response rate was 83% (35/42). The overall response rate was 90% (26/29) in the previously untreated patients and 69% (9/13) in relapsed/refractory patients.

The composite complete response rate was 62% (n=26) overall, 72% (n=21) in previously untreated patients, and 38% (n=5) in relapsed/refractory patients.

Fourteen patients went on to stem cell transplant, 1 of whom had relapsed/refractory disease at baseline.

Overall survival results were only available for the 29 previously untreated patients who received tagraxofusp at 12 μg/kg/day. In this group, the median overall survival had not been reached at a median follow-up of 13.8 months (range, 0.2 to 37.4 months).

Safety results were presented for 114 patients who have received tagraxofusp at 12 μg/kg/day on all trials of the drug. These data include patients with diseases other than BPDCN, although adverse events (AEs) were similar regardless of disease.

Common treatment-related AEs (of any grade, occurring in at least 15% of patients) included hypoalbuminemia (49%), ALT increase (48%), AST increase (48%), thrombocytopenia (29%), nausea (27%), pyrexia (25%), chills (23%), fatigue (23%), weight increase (19%), hypotension (18%), peripheral edema (17%), and vomiting (15%).

Another common AE was capillary leak syndrome (CLS), which occurred in 20% of patients (n=23). Most cases of CLS were grade 1 or 2, but there were grade 3 (n=5) and 4 (n=2) cases, as well as a single case of grade 5 CLS that occurred in a BPDCN patient.

Researchers found they could manage the CLS with monitoring and protocol adjustments.

Photo by Bill Branson

The US Food and Drug Administration(FDA) has accepted for priority review the biologics license application seeking approval for tagraxofusp (Elzonris, SL-401) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The FDA expects to make a decision on this application by February 21, 2019.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

About tagraxofusp

Tagraxofusp is a targeted therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. The drug is being developed by Stemline Therapeutics, Inc.

In addition to priority review, tagraxofusp has breakthrough therapy designation and orphan drug designation from the FDA.

Tagraxofusp has produced favorable early results in a phase 2 trial of patients with BPDCN. Results from this trial were presented at the 23rd Congress of the European Hematology Association (EHA) in June.

Results were presented for 45 patients—32 with previously untreated BPDCN and 13 with relapsed/refractory BPDCN.

Three patients received tagraxofusp at 7 μg/kg/day on days 1 to 5 of a 21-day cycle, and the rest received the drug at 12 μg/kg on days 1 to 5 of a 21-day cycle.

Among patients who received the 12 μg/kg/day dose, the overall response rate was 83% (35/42). The overall response rate was 90% (26/29) in the previously untreated patients and 69% (9/13) in relapsed/refractory patients.

The composite complete response rate was 62% (n=26) overall, 72% (n=21) in previously untreated patients, and 38% (n=5) in relapsed/refractory patients.

Fourteen patients went on to stem cell transplant, 1 of whom had relapsed/refractory disease at baseline.

Overall survival results were only available for the 29 previously untreated patients who received tagraxofusp at 12 μg/kg/day. In this group, the median overall survival had not been reached at a median follow-up of 13.8 months (range, 0.2 to 37.4 months).

Safety results were presented for 114 patients who have received tagraxofusp at 12 μg/kg/day on all trials of the drug. These data include patients with diseases other than BPDCN, although adverse events (AEs) were similar regardless of disease.

Common treatment-related AEs (of any grade, occurring in at least 15% of patients) included hypoalbuminemia (49%), ALT increase (48%), AST increase (48%), thrombocytopenia (29%), nausea (27%), pyrexia (25%), chills (23%), fatigue (23%), weight increase (19%), hypotension (18%), peripheral edema (17%), and vomiting (15%).

Another common AE was capillary leak syndrome (CLS), which occurred in 20% of patients (n=23). Most cases of CLS were grade 1 or 2, but there were grade 3 (n=5) and 4 (n=2) cases, as well as a single case of grade 5 CLS that occurred in a BPDCN patient.

Researchers found they could manage the CLS with monitoring and protocol adjustments.

Photo by Larry Young

Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.

In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.

The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.

Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.

The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.

The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.

Treatment

For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.

The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.

Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.

There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.

The median duration of follow-up was 17.0 months.

Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:

• Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
• AEs (n=28)
• Withdrawn consent (n=13)
• Investigator decision (n=9)
• Patient decision (n=6)
• Death (n=2)
• Noncompliance (n=1).

Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.

Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:

• Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
• Patient decision (n=9)
• Withdrawn consent (n=5)
• AEs (n=5)
• Death (n=2)
• Lost to follow-up (n=1).

At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.

Patient characteristics

Baseline characteristics were similar between the treatment arms.

PFS and ORR

Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in ORR with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Responses by disease compartment were superior with mogamulizumab as well.

The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.

The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.

Crossover

Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.

In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.

Safety

The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Thrombocytopenia (14% vs 34%)
• Diarrhea (23% vs 57%)
• Nausea (15% vs 41%)
• Fatigue (22% vs 32%)
• Increased blood creatinine (3% vs 28%)
• Decreased appetite (7% vs 24%)
• Dysgeusia (3% vs 28%)
• Drug eruptions (20% vs 1%)
• Infusion-related reactions (32% vs 1%).

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo by Larry Young

Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.

In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.

The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.

Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.

The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.

The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.

Treatment

For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.

The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.

Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.

There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.

The median duration of follow-up was 17.0 months.

Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:

• Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
• AEs (n=28)
• Withdrawn consent (n=13)
• Investigator decision (n=9)
• Patient decision (n=6)
• Death (n=2)
• Noncompliance (n=1).

Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.

Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:

• Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
• Patient decision (n=9)
• Withdrawn consent (n=5)
• AEs (n=5)
• Death (n=2)
• Lost to follow-up (n=1).

At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.

Patient characteristics

Baseline characteristics were similar between the treatment arms.

PFS and ORR

Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in ORR with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Responses by disease compartment were superior with mogamulizumab as well.

The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.

The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.

Crossover

Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.

In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.

Safety

The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Thrombocytopenia (14% vs 34%)
• Diarrhea (23% vs 57%)
• Nausea (15% vs 41%)
• Fatigue (22% vs 32%)
• Increased blood creatinine (3% vs 28%)
• Decreased appetite (7% vs 24%)
• Dysgeusia (3% vs 28%)
• Drug eruptions (20% vs 1%)
• Infusion-related reactions (32% vs 1%).

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo by Larry Young

Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.

In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.

The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.

Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.

The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.

The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.

Treatment

For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.

The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.

Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.

There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.

The median duration of follow-up was 17.0 months.

Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:

• Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
• AEs (n=28)
• Withdrawn consent (n=13)
• Investigator decision (n=9)
• Patient decision (n=6)
• Death (n=2)
• Noncompliance (n=1).

Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.

Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:

• Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
• Patient decision (n=9)
• Withdrawn consent (n=5)
• AEs (n=5)
• Death (n=2)
• Lost to follow-up (n=1).

At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.

Patient characteristics

Baseline characteristics were similar between the treatment arms.

PFS and ORR

Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in ORR with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Responses by disease compartment were superior with mogamulizumab as well.

The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.

The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.

Crossover

Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.

In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.

Safety

The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Thrombocytopenia (14% vs 34%)
• Diarrhea (23% vs 57%)
• Nausea (15% vs 41%)
• Fatigue (22% vs 32%)
• Increased blood creatinine (3% vs 28%)
• Decreased appetite (7% vs 24%)
• Dysgeusia (3% vs 28%)
• Drug eruptions (20% vs 1%)
• Infusion-related reactions (32% vs 1%).

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo by Luis Alvaz

Patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) for lymphoma or myeloma have an increased risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to a retrospective study.

The study suggested these patients have 10 to 100 times the risk of AML or MDS as the general population.

The elevated risk also exceeds that of similar lymphoma and myeloma patients largely untreated with auto-HSCT.

Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation in Ohio, and his colleagues reported these findings in Leukemia Research.

The investigators noted that exposure to DNA-damaging drugs and ionizing radiation—both used in auto-HSCT—is known to increase the risk of AML and MDS.

With this in mind, the team analyzed data on auto-HSCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Analyses were based on 9028 patients undergoing auto-HSCT from 1995 to 2010 for Hodgkin lymphoma (n=916), non-Hodgkin lymphoma (NHL, n=3546), or plasma cell myeloma (n=4566). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant.

More aggressive transplant protocols increased the likelihood of this outcome. The risk of developing AML or MDS was higher for:

• Hodgkin lymphoma patients who received conditioning with total body radiation versus chemotherapy alone (hazard ratio [HR], 4.0)
• NHL patients who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen (bischloroethylnitrosourea, etoposide, cytarabine, and melphalan)
• NHL or myeloma patients who received 3 or more lines of chemotherapy versus 1 line (HR, 1.9 for NHL and 1.8 for myeloma)
• NHL patients who underwent transplant in 2005 to 2010 versus 1995 to 1999 (HR, 2.1).

Patients reported to the Surveillance, Epidemiology and End Results database with the same lymphoma and myeloma diagnoses, few of whom underwent auto-HSCT, had risks of AML and MDS that were 5 to 10 times higher than the background level in the population.

However, the study auto-HSCT cohort had a risk of AML that was 10 to 50 times higher and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for [auto-HSCT], but this hypothesis can only be tested in a prospective study,” Dr Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown.

“One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased post-transplant surveillance resulted in a deficiency of AML,” the investigators wrote. “A second is based on steeper MDS versus AML incidences versus age . . . and the possibility that transplantation recipient marrow ages (ie, marrow biological ages) are perhaps decades older than calendar ages.”

The study authors said they had no relevant conflicts of interest. The CIBMTR is supported by several US government agencies and numerous pharmaceutical companies. 

Photo by Luis Alvaz

Patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) for lymphoma or myeloma have an increased risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to a retrospective study.

The study suggested these patients have 10 to 100 times the risk of AML or MDS as the general population.

The elevated risk also exceeds that of similar lymphoma and myeloma patients largely untreated with auto-HSCT.

Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation in Ohio, and his colleagues reported these findings in Leukemia Research.

The investigators noted that exposure to DNA-damaging drugs and ionizing radiation—both used in auto-HSCT—is known to increase the risk of AML and MDS.

With this in mind, the team analyzed data on auto-HSCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Analyses were based on 9028 patients undergoing auto-HSCT from 1995 to 2010 for Hodgkin lymphoma (n=916), non-Hodgkin lymphoma (NHL, n=3546), or plasma cell myeloma (n=4566). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant.

More aggressive transplant protocols increased the likelihood of this outcome. The risk of developing AML or MDS was higher for:

• Hodgkin lymphoma patients who received conditioning with total body radiation versus chemotherapy alone (hazard ratio [HR], 4.0)
• NHL patients who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen (bischloroethylnitrosourea, etoposide, cytarabine, and melphalan)
• NHL or myeloma patients who received 3 or more lines of chemotherapy versus 1 line (HR, 1.9 for NHL and 1.8 for myeloma)
• NHL patients who underwent transplant in 2005 to 2010 versus 1995 to 1999 (HR, 2.1).

Patients reported to the Surveillance, Epidemiology and End Results database with the same lymphoma and myeloma diagnoses, few of whom underwent auto-HSCT, had risks of AML and MDS that were 5 to 10 times higher than the background level in the population.

However, the study auto-HSCT cohort had a risk of AML that was 10 to 50 times higher and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for [auto-HSCT], but this hypothesis can only be tested in a prospective study,” Dr Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown.

“One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased post-transplant surveillance resulted in a deficiency of AML,” the investigators wrote. “A second is based on steeper MDS versus AML incidences versus age . . . and the possibility that transplantation recipient marrow ages (ie, marrow biological ages) are perhaps decades older than calendar ages.”

The study authors said they had no relevant conflicts of interest. The CIBMTR is supported by several US government agencies and numerous pharmaceutical companies. 

Photo by Luis Alvaz

Patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) for lymphoma or myeloma have an increased risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to a retrospective study.

The study suggested these patients have 10 to 100 times the risk of AML or MDS as the general population.

The elevated risk also exceeds that of similar lymphoma and myeloma patients largely untreated with auto-HSCT.

Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation in Ohio, and his colleagues reported these findings in Leukemia Research.

The investigators noted that exposure to DNA-damaging drugs and ionizing radiation—both used in auto-HSCT—is known to increase the risk of AML and MDS.

With this in mind, the team analyzed data on auto-HSCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Analyses were based on 9028 patients undergoing auto-HSCT from 1995 to 2010 for Hodgkin lymphoma (n=916), non-Hodgkin lymphoma (NHL, n=3546), or plasma cell myeloma (n=4566). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant.

More aggressive transplant protocols increased the likelihood of this outcome. The risk of developing AML or MDS was higher for:

• Hodgkin lymphoma patients who received conditioning with total body radiation versus chemotherapy alone (hazard ratio [HR], 4.0)
• NHL patients who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen (bischloroethylnitrosourea, etoposide, cytarabine, and melphalan)
• NHL or myeloma patients who received 3 or more lines of chemotherapy versus 1 line (HR, 1.9 for NHL and 1.8 for myeloma)
• NHL patients who underwent transplant in 2005 to 2010 versus 1995 to 1999 (HR, 2.1).

Patients reported to the Surveillance, Epidemiology and End Results database with the same lymphoma and myeloma diagnoses, few of whom underwent auto-HSCT, had risks of AML and MDS that were 5 to 10 times higher than the background level in the population.

However, the study auto-HSCT cohort had a risk of AML that was 10 to 50 times higher and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for [auto-HSCT], but this hypothesis can only be tested in a prospective study,” Dr Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown.

“One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased post-transplant surveillance resulted in a deficiency of AML,” the investigators wrote. “A second is based on steeper MDS versus AML incidences versus age . . . and the possibility that transplantation recipient marrow ages (ie, marrow biological ages) are perhaps decades older than calendar ages.”

The study authors said they had no relevant conflicts of interest. The CIBMTR is supported by several US government agencies and numerous pharmaceutical companies. 

Three generations of women in a family

A large study has revealed “the strongest evidence yet” supporting genetic susceptibility to myeloid malignancies, according to a researcher.

The study showed that first-degree relatives of patients with myeloid malignancies had double the risk of developing a myeloid malignancy themselves, when compared to the general population.

The researchers observed significant risks for developing acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), essential thrombocythemia (ET), and polycythemia vera (PV).

“Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before, in part, because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said Amit Sud, MBChB, PhD, of The Institute of Cancer Research in London, UK.

Dr Sud and his colleagues described their research in a letter to Blood.

The researchers analyzed data from the Swedish Family-Cancer Database, which included 93,199 first-degree relatives of 35,037 patients with myeloid malignancies. The patients had been diagnosed between 1958 and 2015.

First-degree relatives of the patients had an increased risk of all myeloid malignancies, with a standardized incidence ratio (SIR) of 1.99 (95% CI 1.12-2.04).

For individual diseases, there was a significant association between family history and increased risk for:

• AML—SIR=1.53 (95% CI 1.21-2.17)
• ET—SIR=6.30 (95% CI 3.95-9.54)
• MDS—SIR=6.87 (95% CI 4.07-10.86)
• PV—SIR=7.66 (95% CI 5.74-10.02).

Dr Sud and his colleagues noted that the strongest familial relative risks tended to occur for the same disease, but there were significant associations between different myeloid malignancies as well.

Risk by age group

The researchers also looked at familial relative risk for the same disease by patients’ age at diagnosis and observed a significantly increased risk for younger cases for all myeloproliferative neoplasms (MPNs) combined, PV, and MDS.

The SIRs for MPNs were 6.46 (95% CI 5.12-8.04) for patients age 59 or younger and 4.15 (95% CI 3.38-5.04) for patients older than 59.

The SIRs for PV were 10.90 (95% CI 7.12-15.97) for patients age 59 or younger and 5.96 (95% CI 3.93-8.67) for patients older than 59.

The SIRs for MDS were 11.95 (95% CI 6.36-20.43) for patients age 68 or younger and 3.27 (95% CI 1.06-7.63) for patients older than 68.

Risk by number of relatives

Dr Sud and his colleagues also discovered that familial relative risks of all myeloid malignancies and MPNs were significantly associated with the number of first-degree relatives affected by myeloid malignancies or MPNs.

The SIRs for first-degree relatives with 2 or more affected relatives were 4.55 (95% CI 2.08-8.64) for all myeloid malignancies and 17.82 (95% CI 5.79-24.89) for MPNs.

The SIRs for first-degree relatives with 1 affected relative were 1.96 (95% CI 1.79-2.15) for all myeloid malignancies and 4.83 (95% CI 4.14-5.60) for MPNs.

The researchers said these results suggest inherited genetic changes increase the risk of myeloid malignancies, although environmental factors shared in families could also play a role.

“In the future, our findings could help identify people at higher risk than normal because of their family background who could be prioritized for medical help like screening to catch the disease earlier if it arises,” Dr Sud said.

This study was funded by German Cancer Aid, the Swedish Research Council, ALF funding from Region Skåne, DKFZ, and Bloodwise.

Three generations of women in a family

A large study has revealed “the strongest evidence yet” supporting genetic susceptibility to myeloid malignancies, according to a researcher.

The study showed that first-degree relatives of patients with myeloid malignancies had double the risk of developing a myeloid malignancy themselves, when compared to the general population.

The researchers observed significant risks for developing acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), essential thrombocythemia (ET), and polycythemia vera (PV).

“Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before, in part, because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said Amit Sud, MBChB, PhD, of The Institute of Cancer Research in London, UK.

Dr Sud and his colleagues described their research in a letter to Blood.

The researchers analyzed data from the Swedish Family-Cancer Database, which included 93,199 first-degree relatives of 35,037 patients with myeloid malignancies. The patients had been diagnosed between 1958 and 2015.

First-degree relatives of the patients had an increased risk of all myeloid malignancies, with a standardized incidence ratio (SIR) of 1.99 (95% CI 1.12-2.04).

For individual diseases, there was a significant association between family history and increased risk for:

• AML—SIR=1.53 (95% CI 1.21-2.17)
• ET—SIR=6.30 (95% CI 3.95-9.54)
• MDS—SIR=6.87 (95% CI 4.07-10.86)
• PV—SIR=7.66 (95% CI 5.74-10.02).

Dr Sud and his colleagues noted that the strongest familial relative risks tended to occur for the same disease, but there were significant associations between different myeloid malignancies as well.

Risk by age group

The researchers also looked at familial relative risk for the same disease by patients’ age at diagnosis and observed a significantly increased risk for younger cases for all myeloproliferative neoplasms (MPNs) combined, PV, and MDS.

The SIRs for MPNs were 6.46 (95% CI 5.12-8.04) for patients age 59 or younger and 4.15 (95% CI 3.38-5.04) for patients older than 59.

The SIRs for PV were 10.90 (95% CI 7.12-15.97) for patients age 59 or younger and 5.96 (95% CI 3.93-8.67) for patients older than 59.

The SIRs for MDS were 11.95 (95% CI 6.36-20.43) for patients age 68 or younger and 3.27 (95% CI 1.06-7.63) for patients older than 68.

Risk by number of relatives

Dr Sud and his colleagues also discovered that familial relative risks of all myeloid malignancies and MPNs were significantly associated with the number of first-degree relatives affected by myeloid malignancies or MPNs.

The SIRs for first-degree relatives with 2 or more affected relatives were 4.55 (95% CI 2.08-8.64) for all myeloid malignancies and 17.82 (95% CI 5.79-24.89) for MPNs.

The SIRs for first-degree relatives with 1 affected relative were 1.96 (95% CI 1.79-2.15) for all myeloid malignancies and 4.83 (95% CI 4.14-5.60) for MPNs.

The researchers said these results suggest inherited genetic changes increase the risk of myeloid malignancies, although environmental factors shared in families could also play a role.

“In the future, our findings could help identify people at higher risk than normal because of their family background who could be prioritized for medical help like screening to catch the disease earlier if it arises,” Dr Sud said.

This study was funded by German Cancer Aid, the Swedish Research Council, ALF funding from Region Skåne, DKFZ, and Bloodwise.

Three generations of women in a family

A large study has revealed “the strongest evidence yet” supporting genetic susceptibility to myeloid malignancies, according to a researcher.

The study showed that first-degree relatives of patients with myeloid malignancies had double the risk of developing a myeloid malignancy themselves, when compared to the general population.

The researchers observed significant risks for developing acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), essential thrombocythemia (ET), and polycythemia vera (PV).

“Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before, in part, because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said Amit Sud, MBChB, PhD, of The Institute of Cancer Research in London, UK.

Dr Sud and his colleagues described their research in a letter to Blood.

The researchers analyzed data from the Swedish Family-Cancer Database, which included 93,199 first-degree relatives of 35,037 patients with myeloid malignancies. The patients had been diagnosed between 1958 and 2015.

First-degree relatives of the patients had an increased risk of all myeloid malignancies, with a standardized incidence ratio (SIR) of 1.99 (95% CI 1.12-2.04).

For individual diseases, there was a significant association between family history and increased risk for:

• AML—SIR=1.53 (95% CI 1.21-2.17)
• ET—SIR=6.30 (95% CI 3.95-9.54)
• MDS—SIR=6.87 (95% CI 4.07-10.86)
• PV—SIR=7.66 (95% CI 5.74-10.02).

Dr Sud and his colleagues noted that the strongest familial relative risks tended to occur for the same disease, but there were significant associations between different myeloid malignancies as well.

Risk by age group

The researchers also looked at familial relative risk for the same disease by patients’ age at diagnosis and observed a significantly increased risk for younger cases for all myeloproliferative neoplasms (MPNs) combined, PV, and MDS.

The SIRs for MPNs were 6.46 (95% CI 5.12-8.04) for patients age 59 or younger and 4.15 (95% CI 3.38-5.04) for patients older than 59.

The SIRs for PV were 10.90 (95% CI 7.12-15.97) for patients age 59 or younger and 5.96 (95% CI 3.93-8.67) for patients older than 59.

The SIRs for MDS were 11.95 (95% CI 6.36-20.43) for patients age 68 or younger and 3.27 (95% CI 1.06-7.63) for patients older than 68.

Risk by number of relatives

Dr Sud and his colleagues also discovered that familial relative risks of all myeloid malignancies and MPNs were significantly associated with the number of first-degree relatives affected by myeloid malignancies or MPNs.

The SIRs for first-degree relatives with 2 or more affected relatives were 4.55 (95% CI 2.08-8.64) for all myeloid malignancies and 17.82 (95% CI 5.79-24.89) for MPNs.

The SIRs for first-degree relatives with 1 affected relative were 1.96 (95% CI 1.79-2.15) for all myeloid malignancies and 4.83 (95% CI 4.14-5.60) for MPNs.

The researchers said these results suggest inherited genetic changes increase the risk of myeloid malignancies, although environmental factors shared in families could also play a role.

“In the future, our findings could help identify people at higher risk than normal because of their family background who could be prioritized for medical help like screening to catch the disease earlier if it arises,” Dr Sud said.

This study was funded by German Cancer Aid, the Swedish Research Council, ALF funding from Region Skåne, DKFZ, and Bloodwise.

Photo by Bill Branson

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for fit patients with chronic lymphocytic leukemia (CLL) who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on CLL to include “significant” developments in treatment.

The new guidelines were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the University of Oxford in the UK, and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible, patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who cannot take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients can also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended.

TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib plus rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote.

However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplant should be considered as an option for patients who have failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have Richter’s transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5% to 10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum, which was involved in development as well, is a registered charity that receives funding from a number of pharmaceutical companies.

Photo by Bill Branson

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for fit patients with chronic lymphocytic leukemia (CLL) who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on CLL to include “significant” developments in treatment.

The new guidelines were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the University of Oxford in the UK, and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible, patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who cannot take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients can also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended.

TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib plus rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote.

However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplant should be considered as an option for patients who have failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have Richter’s transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5% to 10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum, which was involved in development as well, is a registered charity that receives funding from a number of pharmaceutical companies.

Photo by Bill Branson

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for fit patients with chronic lymphocytic leukemia (CLL) who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on CLL to include “significant” developments in treatment.

The new guidelines were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the University of Oxford in the UK, and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible, patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who cannot take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients can also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended.

TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib plus rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote.

However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplant should be considered as an option for patients who have failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have Richter’s transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5% to 10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum, which was involved in development as well, is a registered charity that receives funding from a number of pharmaceutical companies.

Photo courtesy of the CDC

Having health insurance can mean the difference between life and death for US patients with follicular lymphoma (FL), according to research published in Blood.

The study showed that patients with private health insurance had nearly 2-fold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

A review of records on more than 43,000 FL patients showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket were 1.96 for those with no insurance, 1.83 for those with Medicaid, and 1.96 for those with Medicare (P<0.0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL,” Christopher R. Flowers, MD, of Emory University in Atlanta, Georgia, and his colleagues wrote in Blood.

“Future studies on outcomes in FL should include insurance status as an important predictor. Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability.”

Earlier research showed that patients with Medicaid or no insurance were more likely than privately insured patients to be diagnosed with cancers at advanced stages, and some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, Dr Flowers and his colleagues extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

The investigators identified 43,648 patients, age 18 and older, who were diagnosed with FL from 2004 through 2014. The team looked at patients ages 18 to 64 as well as patients age 65 and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients age 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P<0.0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and patients with a score of 2 or greater had an HR of 3.1 (P<0.0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality healthcare may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

Photo courtesy of the CDC

Having health insurance can mean the difference between life and death for US patients with follicular lymphoma (FL), according to research published in Blood.

The study showed that patients with private health insurance had nearly 2-fold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

A review of records on more than 43,000 FL patients showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket were 1.96 for those with no insurance, 1.83 for those with Medicaid, and 1.96 for those with Medicare (P<0.0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL,” Christopher R. Flowers, MD, of Emory University in Atlanta, Georgia, and his colleagues wrote in Blood.

“Future studies on outcomes in FL should include insurance status as an important predictor. Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability.”

Earlier research showed that patients with Medicaid or no insurance were more likely than privately insured patients to be diagnosed with cancers at advanced stages, and some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, Dr Flowers and his colleagues extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

The investigators identified 43,648 patients, age 18 and older, who were diagnosed with FL from 2004 through 2014. The team looked at patients ages 18 to 64 as well as patients age 65 and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients age 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P<0.0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and patients with a score of 2 or greater had an HR of 3.1 (P<0.0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality healthcare may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

Photo courtesy of the CDC

Having health insurance can mean the difference between life and death for US patients with follicular lymphoma (FL), according to research published in Blood.

The study showed that patients with private health insurance had nearly 2-fold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

A review of records on more than 43,000 FL patients showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket were 1.96 for those with no insurance, 1.83 for those with Medicaid, and 1.96 for those with Medicare (P<0.0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL,” Christopher R. Flowers, MD, of Emory University in Atlanta, Georgia, and his colleagues wrote in Blood.

“Future studies on outcomes in FL should include insurance status as an important predictor. Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability.”

Earlier research showed that patients with Medicaid or no insurance were more likely than privately insured patients to be diagnosed with cancers at advanced stages, and some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, Dr Flowers and his colleagues extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

The investigators identified 43,648 patients, age 18 and older, who were diagnosed with FL from 2004 through 2014. The team looked at patients ages 18 to 64 as well as patients age 65 and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients age 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P<0.0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and patients with a score of 2 or greater had an HR of 3.1 (P<0.0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality healthcare may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.