Leukemia, Myelodysplasia, Transplantation

Crowd at ASCO 2015

© ASCO/Rodney White

CHICAGO—Researchers say they have identified 3 leukemia stem cell (LSC) phenotypes that are correlated with cytogenetic/molecular abnormalities and prognosis in acute myeloid leukemia (AML).

The investigators believe this knowledge could aid risk stratification of AML patients, particularly those without identifiable cytogenetic or molecular risk factors.

The findings may also pave the way for scientists to identify novel therapeutic targets on LSCs and monitor LSCs in response to therapy.

Jonathan Michael Gerber, MD, of Levine Cancer Institute in Charlotte, North Carolina, presented the findings at the 2015 ASCO Annual Meeting (abstract 7000*).

Via previous research, Dr Gerber and his colleagues identified 3 different LSC phenotypes in AML:

• LSCs that are CD34-negative
• LSCs that are CD34-positive, CD38-negative, and have intermediate levels of aldehyde dehydrogenase (ALDH^int)
• LSCs that are CD34-positive, CD38-negative, and have high levels of ALDH (ALDH^high).

With the current study, the researchers wanted to determine if these phenotypes correlate with cytogenetic/molecular features and treatment outcomes.

So they analyzed diagnostic samples from 98 patients with newly diagnosed AML who had normal or unfavorable cytogenetics. The patients were enrolled on a phase 2 trial comparing FLAM and 7+3 (Zeidner et al, haematologica 2015).

Dr Gerber and his colleagues identified 22 patients with CD34^- LSCs, 43 with ALDH^int LSCs, and 33 with ALDH^high LSCs.

Risk factors

“We found that leukemia stem cell phenotype indeed correlated quite strongly with cytogenetic and molecular risk factors,” Dr Gerber said.

NPM1 mutations were more common in patients with CD34^- LSCs (64%) than those with ALDH^int LSCs (14%) or ALDH^high LSCs (6%, P<0.001). NPM1 mutations were the sole abnormality in 50% of patients with CD34^- LSCs.

Poor-risk cytogenetics and/or FLT3-ITD mutations were more common in patients with ALDH^high LSCs (85%) than those with ALDH^int LCSs (35%) or CD34^- LSCs (18%, P<0.001).

Nine percent of patients in the CD34^- LSC group fell into the European Leukemia Network poor-risk category, compared to 73% of patients in the ALDH^high LSC group.

Only 2 patients had 11q23, and both had CD34^- LSCs. Fifty-five percent of patients with ALDH^high LSCs had prior myelodysplastic syndromes or myeloproliferative neoplasms.

Prognosis

“We found that leukemia stem cell phenotype correlated strongly with outcomes as well,” Dr Gerber said. “It turned out that CD34^- patients fared more favorably overall.”

Patients with CD34^- LSCs had the highest complete response rate (86%), followed by those with ALDH^int LSCs (67%) and ALDH^high LSCs (45%, P<0.01).

Patients in the CD34^- group also had a higher rate of event-free survival at 2 years (46%) than patients in the ALDH^int group (26%) or the ALDH^high group (0%). The median event-free survival was 13 months, 11.3 months, and 2.2 months, respectively (P<0.01).

The rate of overall survival at 2 years was best for the CD34^- group (76%), followed by the ALDH^int group (38%) and the ALDH^high group (34%). The median overall survival was not reached, 18.7 months, and 9.4 months, respectively (P=0.02).

Dr Gerber also noted that ALDH^high patients fared much better if they underwent hematopoietic stem cell transplant.

“There is 0% leukemia-free survival at the 2-year mark for the ALDH^high patients who were not transplanted,” he said. “Those that were transplanted fared about the same as everyone else in the series. So it was very striking that there were no chemotherapy survivors in that group.”

In closing, Dr Gerber said this research suggests the 3 LSC phenotypes are mutually exclusive and correlate with cytogenetic and molecular risk factors as well as outcomes in patients with AML.

“This [discovery] may allow for rapid risk stratification in this explosive disease, facilitate enrollment onto induction protocols . . . , and allow us to divert those ALDH^high, very high-risk patients earlier to novel therapies and/or transplant, given that they’re not really helped much by conventional chemotherapy.”

*Information in the abstract differs from that presented at the meeting.

Crowd at ASCO 2015

© ASCO/Rodney White

CHICAGO—Researchers say they have identified 3 leukemia stem cell (LSC) phenotypes that are correlated with cytogenetic/molecular abnormalities and prognosis in acute myeloid leukemia (AML).

The investigators believe this knowledge could aid risk stratification of AML patients, particularly those without identifiable cytogenetic or molecular risk factors.

The findings may also pave the way for scientists to identify novel therapeutic targets on LSCs and monitor LSCs in response to therapy.

Jonathan Michael Gerber, MD, of Levine Cancer Institute in Charlotte, North Carolina, presented the findings at the 2015 ASCO Annual Meeting (abstract 7000*).

Via previous research, Dr Gerber and his colleagues identified 3 different LSC phenotypes in AML:

• LSCs that are CD34-negative
• LSCs that are CD34-positive, CD38-negative, and have intermediate levels of aldehyde dehydrogenase (ALDH^int)
• LSCs that are CD34-positive, CD38-negative, and have high levels of ALDH (ALDH^high).

With the current study, the researchers wanted to determine if these phenotypes correlate with cytogenetic/molecular features and treatment outcomes.

So they analyzed diagnostic samples from 98 patients with newly diagnosed AML who had normal or unfavorable cytogenetics. The patients were enrolled on a phase 2 trial comparing FLAM and 7+3 (Zeidner et al, haematologica 2015).

Dr Gerber and his colleagues identified 22 patients with CD34^- LSCs, 43 with ALDH^int LSCs, and 33 with ALDH^high LSCs.

Risk factors

“We found that leukemia stem cell phenotype indeed correlated quite strongly with cytogenetic and molecular risk factors,” Dr Gerber said.

NPM1 mutations were more common in patients with CD34^- LSCs (64%) than those with ALDH^int LSCs (14%) or ALDH^high LSCs (6%, P<0.001). NPM1 mutations were the sole abnormality in 50% of patients with CD34^- LSCs.

Poor-risk cytogenetics and/or FLT3-ITD mutations were more common in patients with ALDH^high LSCs (85%) than those with ALDH^int LCSs (35%) or CD34^- LSCs (18%, P<0.001).

Nine percent of patients in the CD34^- LSC group fell into the European Leukemia Network poor-risk category, compared to 73% of patients in the ALDH^high LSC group.

Only 2 patients had 11q23, and both had CD34^- LSCs. Fifty-five percent of patients with ALDH^high LSCs had prior myelodysplastic syndromes or myeloproliferative neoplasms.

Prognosis

“We found that leukemia stem cell phenotype correlated strongly with outcomes as well,” Dr Gerber said. “It turned out that CD34^- patients fared more favorably overall.”

Patients with CD34^- LSCs had the highest complete response rate (86%), followed by those with ALDH^int LSCs (67%) and ALDH^high LSCs (45%, P<0.01).

Patients in the CD34^- group also had a higher rate of event-free survival at 2 years (46%) than patients in the ALDH^int group (26%) or the ALDH^high group (0%). The median event-free survival was 13 months, 11.3 months, and 2.2 months, respectively (P<0.01).

The rate of overall survival at 2 years was best for the CD34^- group (76%), followed by the ALDH^int group (38%) and the ALDH^high group (34%). The median overall survival was not reached, 18.7 months, and 9.4 months, respectively (P=0.02).

Dr Gerber also noted that ALDH^high patients fared much better if they underwent hematopoietic stem cell transplant.

“There is 0% leukemia-free survival at the 2-year mark for the ALDH^high patients who were not transplanted,” he said. “Those that were transplanted fared about the same as everyone else in the series. So it was very striking that there were no chemotherapy survivors in that group.”

In closing, Dr Gerber said this research suggests the 3 LSC phenotypes are mutually exclusive and correlate with cytogenetic and molecular risk factors as well as outcomes in patients with AML.

“This [discovery] may allow for rapid risk stratification in this explosive disease, facilitate enrollment onto induction protocols . . . , and allow us to divert those ALDH^high, very high-risk patients earlier to novel therapies and/or transplant, given that they’re not really helped much by conventional chemotherapy.”

*Information in the abstract differs from that presented at the meeting.

Crowd at ASCO 2015

© ASCO/Rodney White

CHICAGO—Researchers say they have identified 3 leukemia stem cell (LSC) phenotypes that are correlated with cytogenetic/molecular abnormalities and prognosis in acute myeloid leukemia (AML).

The investigators believe this knowledge could aid risk stratification of AML patients, particularly those without identifiable cytogenetic or molecular risk factors.

The findings may also pave the way for scientists to identify novel therapeutic targets on LSCs and monitor LSCs in response to therapy.

Jonathan Michael Gerber, MD, of Levine Cancer Institute in Charlotte, North Carolina, presented the findings at the 2015 ASCO Annual Meeting (abstract 7000*).

Via previous research, Dr Gerber and his colleagues identified 3 different LSC phenotypes in AML:

• LSCs that are CD34-negative
• LSCs that are CD34-positive, CD38-negative, and have intermediate levels of aldehyde dehydrogenase (ALDH^int)
• LSCs that are CD34-positive, CD38-negative, and have high levels of ALDH (ALDH^high).

With the current study, the researchers wanted to determine if these phenotypes correlate with cytogenetic/molecular features and treatment outcomes.

So they analyzed diagnostic samples from 98 patients with newly diagnosed AML who had normal or unfavorable cytogenetics. The patients were enrolled on a phase 2 trial comparing FLAM and 7+3 (Zeidner et al, haematologica 2015).

Dr Gerber and his colleagues identified 22 patients with CD34^- LSCs, 43 with ALDH^int LSCs, and 33 with ALDH^high LSCs.

Risk factors

“We found that leukemia stem cell phenotype indeed correlated quite strongly with cytogenetic and molecular risk factors,” Dr Gerber said.

NPM1 mutations were more common in patients with CD34^- LSCs (64%) than those with ALDH^int LSCs (14%) or ALDH^high LSCs (6%, P<0.001). NPM1 mutations were the sole abnormality in 50% of patients with CD34^- LSCs.

Poor-risk cytogenetics and/or FLT3-ITD mutations were more common in patients with ALDH^high LSCs (85%) than those with ALDH^int LCSs (35%) or CD34^- LSCs (18%, P<0.001).

Nine percent of patients in the CD34^- LSC group fell into the European Leukemia Network poor-risk category, compared to 73% of patients in the ALDH^high LSC group.

Only 2 patients had 11q23, and both had CD34^- LSCs. Fifty-five percent of patients with ALDH^high LSCs had prior myelodysplastic syndromes or myeloproliferative neoplasms.

Prognosis

“We found that leukemia stem cell phenotype correlated strongly with outcomes as well,” Dr Gerber said. “It turned out that CD34^- patients fared more favorably overall.”

Patients with CD34^- LSCs had the highest complete response rate (86%), followed by those with ALDH^int LSCs (67%) and ALDH^high LSCs (45%, P<0.01).

Patients in the CD34^- group also had a higher rate of event-free survival at 2 years (46%) than patients in the ALDH^int group (26%) or the ALDH^high group (0%). The median event-free survival was 13 months, 11.3 months, and 2.2 months, respectively (P<0.01).

The rate of overall survival at 2 years was best for the CD34^- group (76%), followed by the ALDH^int group (38%) and the ALDH^high group (34%). The median overall survival was not reached, 18.7 months, and 9.4 months, respectively (P=0.02).

Dr Gerber also noted that ALDH^high patients fared much better if they underwent hematopoietic stem cell transplant.

“There is 0% leukemia-free survival at the 2-year mark for the ALDH^high patients who were not transplanted,” he said. “Those that were transplanted fared about the same as everyone else in the series. So it was very striking that there were no chemotherapy survivors in that group.”

In closing, Dr Gerber said this research suggests the 3 LSC phenotypes are mutually exclusive and correlate with cytogenetic and molecular risk factors as well as outcomes in patients with AML.

“This [discovery] may allow for rapid risk stratification in this explosive disease, facilitate enrollment onto induction protocols . . . , and allow us to divert those ALDH^high, very high-risk patients earlier to novel therapies and/or transplant, given that they’re not really helped much by conventional chemotherapy.”

*Information in the abstract differs from that presented at the meeting.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Cancer survivors’ moods are impacted—both positively and negatively—by their spouses’ moods, according to research published in Cancer Epidemiology, Biomarkers & Prevention.

In the study, cancer survivors whose spouses reported depressed moods were more likely to be depressed after about a year of follow-up, and survivors whose spouses reported better mental and physical health-related quality of life (HRQOL) were less likely to be depressed.

However, survivors’ moods did not have the same impact on their spouses.

“We were surprised that the effects of the spouses on the survivors were so much larger in this study than the effect of the survivors on their spouses,” said study author Kristin Litzelman, PhD, of the National Cancer Institute in Bethesda, Maryland. “We expected to see a more reciprocal relationship.”

Dr Litzelman and her colleagues conducted this research in an attempt to understand how cancer survivors and their families influence one another. The team hoped to identify ways to improve the healthcare both parties receive and thereby improve their health and well-being.

The researchers analyzed data from 910 cancer patients and their spouses, comparing them to 910 couples without any kind of cancer-related health problem.

The team used statistical models to assess how each spouse’s quality of life or depression at one time point was associated with his or her partner’s risk of depression around 11 months later. The researchers took into account a person’s previously reported mood, demographic characteristics, and other factors.

The results showed that, when spouses reported feeling depressed, cancer survivors were about 4 times more likely to report being depressed 11 months later (odds ratio [OR]=4.27). This association was stronger among female cancer survivors (OR=9.49) than male survivors (OR=3.98).

Cancer survivors whose spouses reported better HRQOL had a 30% decrease in depressed mood per 10-point improvement in HRQOL score. The ORs were 0.72 for mental health and 0.68 for physical health. The associations between spousal HRQOL and survivor depressed mood were similar for male and female survivors.

The researchers noted that cancer survivors’ moods did not have a significant impact on their spouses’ risk of depressed mood 11 months later.

And the team did not see mood associations in couples without any cancer-related health problems.

“This finding certainly needs to be backed up by other studies, but it highlights the importance of family well-being in cancer survivor outcomes,” Dr Litzelman said. “Our research highlights that spouses need to take care of themselves, not just for their own sake, but also for the sake of the cancer survivor.”

“Our findings also suggest that, when caring for cancer survivors, clinicians may want to assess the well-being of spousal caregivers. Future research could test whether including caregivers in the survivorship care plan might help to improve outcomes for both caregivers and for cancer survivors.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Cancer survivors’ moods are impacted—both positively and negatively—by their spouses’ moods, according to research published in Cancer Epidemiology, Biomarkers & Prevention.

In the study, cancer survivors whose spouses reported depressed moods were more likely to be depressed after about a year of follow-up, and survivors whose spouses reported better mental and physical health-related quality of life (HRQOL) were less likely to be depressed.

However, survivors’ moods did not have the same impact on their spouses.

“We were surprised that the effects of the spouses on the survivors were so much larger in this study than the effect of the survivors on their spouses,” said study author Kristin Litzelman, PhD, of the National Cancer Institute in Bethesda, Maryland. “We expected to see a more reciprocal relationship.”

Dr Litzelman and her colleagues conducted this research in an attempt to understand how cancer survivors and their families influence one another. The team hoped to identify ways to improve the healthcare both parties receive and thereby improve their health and well-being.

The researchers analyzed data from 910 cancer patients and their spouses, comparing them to 910 couples without any kind of cancer-related health problem.

The team used statistical models to assess how each spouse’s quality of life or depression at one time point was associated with his or her partner’s risk of depression around 11 months later. The researchers took into account a person’s previously reported mood, demographic characteristics, and other factors.

The results showed that, when spouses reported feeling depressed, cancer survivors were about 4 times more likely to report being depressed 11 months later (odds ratio [OR]=4.27). This association was stronger among female cancer survivors (OR=9.49) than male survivors (OR=3.98).

Cancer survivors whose spouses reported better HRQOL had a 30% decrease in depressed mood per 10-point improvement in HRQOL score. The ORs were 0.72 for mental health and 0.68 for physical health. The associations between spousal HRQOL and survivor depressed mood were similar for male and female survivors.

The researchers noted that cancer survivors’ moods did not have a significant impact on their spouses’ risk of depressed mood 11 months later.

And the team did not see mood associations in couples without any cancer-related health problems.

“This finding certainly needs to be backed up by other studies, but it highlights the importance of family well-being in cancer survivor outcomes,” Dr Litzelman said. “Our research highlights that spouses need to take care of themselves, not just for their own sake, but also for the sake of the cancer survivor.”

“Our findings also suggest that, when caring for cancer survivors, clinicians may want to assess the well-being of spousal caregivers. Future research could test whether including caregivers in the survivorship care plan might help to improve outcomes for both caregivers and for cancer survivors.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Cancer survivors’ moods are impacted—both positively and negatively—by their spouses’ moods, according to research published in Cancer Epidemiology, Biomarkers & Prevention.

In the study, cancer survivors whose spouses reported depressed moods were more likely to be depressed after about a year of follow-up, and survivors whose spouses reported better mental and physical health-related quality of life (HRQOL) were less likely to be depressed.

However, survivors’ moods did not have the same impact on their spouses.

“We were surprised that the effects of the spouses on the survivors were so much larger in this study than the effect of the survivors on their spouses,” said study author Kristin Litzelman, PhD, of the National Cancer Institute in Bethesda, Maryland. “We expected to see a more reciprocal relationship.”

Dr Litzelman and her colleagues conducted this research in an attempt to understand how cancer survivors and their families influence one another. The team hoped to identify ways to improve the healthcare both parties receive and thereby improve their health and well-being.

The researchers analyzed data from 910 cancer patients and their spouses, comparing them to 910 couples without any kind of cancer-related health problem.

The team used statistical models to assess how each spouse’s quality of life or depression at one time point was associated with his or her partner’s risk of depression around 11 months later. The researchers took into account a person’s previously reported mood, demographic characteristics, and other factors.

The results showed that, when spouses reported feeling depressed, cancer survivors were about 4 times more likely to report being depressed 11 months later (odds ratio [OR]=4.27). This association was stronger among female cancer survivors (OR=9.49) than male survivors (OR=3.98).

Cancer survivors whose spouses reported better HRQOL had a 30% decrease in depressed mood per 10-point improvement in HRQOL score. The ORs were 0.72 for mental health and 0.68 for physical health. The associations between spousal HRQOL and survivor depressed mood were similar for male and female survivors.

The researchers noted that cancer survivors’ moods did not have a significant impact on their spouses’ risk of depressed mood 11 months later.

And the team did not see mood associations in couples without any cancer-related health problems.

“This finding certainly needs to be backed up by other studies, but it highlights the importance of family well-being in cancer survivor outcomes,” Dr Litzelman said. “Our research highlights that spouses need to take care of themselves, not just for their own sake, but also for the sake of the cancer survivor.”

“Our findings also suggest that, when caring for cancer survivors, clinicians may want to assess the well-being of spousal caregivers. Future research could test whether including caregivers in the survivorship care plan might help to improve outcomes for both caregivers and for cancer survivors.”

Breastfeeding baby

Photo by Petr Kratochvil

Breastfeeding a child may reduce his risk of developing acute lymphoblastic leukemia (ALL) but perhaps not acute myeloid leukemia (AML), according to a review published in JAMA Pediatrics.

Researchers found that breastfeeding a child for 6 months or longer was associated with a 19% lower risk of childhood leukemia, compared with no

breastfeeding or breastfeeding for a shorter period of time.

And children who were breastfed for any amount of time had an 11% lower risk of childhood leukemia than children who were never breastfed.

However, when the researchers analyzed studies of ALL and AML separately, they found that breastfeeding was not associated with a significantly lower risk of AML.

Efrat L. Amitay, PhD, and Lital Keinan-Boker, MD, PhD, of the University of Haifa in Israel, conducted this research.

In a review of 18 studies, the pair found that breastfeeding a child for 6 months or longer was associated with a significantly lower risk of childhood leukemia, compared with no breastfeeding or breastfeeding for a shorter period of time (odds ratio [OR]=0.81).

And a separate analysis of 15 studies showed that children who were breastfed for any amount of time had a lower risk of childhood leukemia than children who were never breastfed (OR=0.89).

The researchers also conducted meta-analyses of AML studies and ALL studies separately—11 ALL and 6 AML studies. And they found a significant inverse association between breastfeeding for 6 months or more and ALL risk (OR=0.82) but no significant association for AML risk (OR=0.74).

The researchers said several biological mechanisms may explain the association between breastfeeding and a reduced risk of childhood leukemia. However, more high-quality studies are needed to clarify those mechanisms.

Breastfeeding baby

Photo by Petr Kratochvil

Breastfeeding a child may reduce his risk of developing acute lymphoblastic leukemia (ALL) but perhaps not acute myeloid leukemia (AML), according to a review published in JAMA Pediatrics.

Researchers found that breastfeeding a child for 6 months or longer was associated with a 19% lower risk of childhood leukemia, compared with no

breastfeeding or breastfeeding for a shorter period of time.

And children who were breastfed for any amount of time had an 11% lower risk of childhood leukemia than children who were never breastfed.

However, when the researchers analyzed studies of ALL and AML separately, they found that breastfeeding was not associated with a significantly lower risk of AML.

Efrat L. Amitay, PhD, and Lital Keinan-Boker, MD, PhD, of the University of Haifa in Israel, conducted this research.

In a review of 18 studies, the pair found that breastfeeding a child for 6 months or longer was associated with a significantly lower risk of childhood leukemia, compared with no breastfeeding or breastfeeding for a shorter period of time (odds ratio [OR]=0.81).

And a separate analysis of 15 studies showed that children who were breastfed for any amount of time had a lower risk of childhood leukemia than children who were never breastfed (OR=0.89).

The researchers also conducted meta-analyses of AML studies and ALL studies separately—11 ALL and 6 AML studies. And they found a significant inverse association between breastfeeding for 6 months or more and ALL risk (OR=0.82) but no significant association for AML risk (OR=0.74).

The researchers said several biological mechanisms may explain the association between breastfeeding and a reduced risk of childhood leukemia. However, more high-quality studies are needed to clarify those mechanisms.

Breastfeeding baby

Photo by Petr Kratochvil

Breastfeeding a child may reduce his risk of developing acute lymphoblastic leukemia (ALL) but perhaps not acute myeloid leukemia (AML), according to a review published in JAMA Pediatrics.

Researchers found that breastfeeding a child for 6 months or longer was associated with a 19% lower risk of childhood leukemia, compared with no

breastfeeding or breastfeeding for a shorter period of time.

And children who were breastfed for any amount of time had an 11% lower risk of childhood leukemia than children who were never breastfed.

However, when the researchers analyzed studies of ALL and AML separately, they found that breastfeeding was not associated with a significantly lower risk of AML.

Efrat L. Amitay, PhD, and Lital Keinan-Boker, MD, PhD, of the University of Haifa in Israel, conducted this research.

In a review of 18 studies, the pair found that breastfeeding a child for 6 months or longer was associated with a significantly lower risk of childhood leukemia, compared with no breastfeeding or breastfeeding for a shorter period of time (odds ratio [OR]=0.81).

And a separate analysis of 15 studies showed that children who were breastfed for any amount of time had a lower risk of childhood leukemia than children who were never breastfed (OR=0.89).

The researchers also conducted meta-analyses of AML studies and ALL studies separately—11 ALL and 6 AML studies. And they found a significant inverse association between breastfeeding for 6 months or more and ALL risk (OR=0.82) but no significant association for AML risk (OR=0.74).

The researchers said several biological mechanisms may explain the association between breastfeeding and a reduced risk of childhood leukemia. However, more high-quality studies are needed to clarify those mechanisms.

In his monthly podcast for The Journal of Community and Supportive Oncology, Dr David Henry looks at Original Reports on the treatment of metastatic breast cancer with nab-paclitaxel in the community practice setting; health professionals’ attitudes toward detecting and managing cancer-related anorexia-cachexia syndrome; the factors associated with symptom-related emergency department visits and hospital admissions during ambulatory cancer treatment; and differences in treatment between urban and rural women with hormone receptor-positive early-stage breast cancer. He also discusses a case report on a patient with severe chemotherapy-induced peripheral neuropathy who experienced a significant response to lacosamide, and Community Translations item using blinatumomab for hard-to-treat acute lymphoblastic leukemia.  

In his monthly podcast for The Journal of Community and Supportive Oncology, Dr David Henry looks at Original Reports on the treatment of metastatic breast cancer with nab-paclitaxel in the community practice setting; health professionals’ attitudes toward detecting and managing cancer-related anorexia-cachexia syndrome; the factors associated with symptom-related emergency department visits and hospital admissions during ambulatory cancer treatment; and differences in treatment between urban and rural women with hormone receptor-positive early-stage breast cancer. He also discusses a case report on a patient with severe chemotherapy-induced peripheral neuropathy who experienced a significant response to lacosamide, and Community Translations item using blinatumomab for hard-to-treat acute lymphoblastic leukemia.  

In his monthly podcast for The Journal of Community and Supportive Oncology, Dr David Henry looks at Original Reports on the treatment of metastatic breast cancer with nab-paclitaxel in the community practice setting; health professionals’ attitudes toward detecting and managing cancer-related anorexia-cachexia syndrome; the factors associated with symptom-related emergency department visits and hospital admissions during ambulatory cancer treatment; and differences in treatment between urban and rural women with hormone receptor-positive early-stage breast cancer. He also discusses a case report on a patient with severe chemotherapy-induced peripheral neuropathy who experienced a significant response to lacosamide, and Community Translations item using blinatumomab for hard-to-treat acute lymphoblastic leukemia.  

Asher Alban Akmal

Chanan-Khan, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.

There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.

“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.

Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.

The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.

Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.

“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”

Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).

Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.

Response and survival

The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).

At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).

“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”

Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.

The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.

The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).

Adverse events

Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.

The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).

The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).

Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.

The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.

Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.

Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.

“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”

Asher Alban Akmal

Chanan-Khan, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.

There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.

“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.

Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.

The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.

Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.

“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”

Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).

Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.

Response and survival

The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).

At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).

“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”

Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.

The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.

The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).

Adverse events

Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.

The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).

The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).

Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.

The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.

Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.

Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.

“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”

Asher Alban Akmal

Chanan-Khan, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.

There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.

“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.

Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.

The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.

Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.

“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”

Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).

Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.

Response and survival

The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).

At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).

“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”

Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.

The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.

The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).

Adverse events

Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.

The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).

The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).

Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.

The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.

Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.

Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.

“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Cynomolgus monkey

Photo by Sakurai Midori

An artificial antibody that redirects T cells to target cancer cells shows promise for treating acute myeloid leukemia (AML), according to preclinical research.

The antibody, MGD006, induced tumor regression in mouse models of AML and was largely well-tolerated in cynomolgus monkeys.

Investigators say these results support clinical testing of MGD006 in AML, which is currently underway.

MGD006 is a humanized, dual-affinity re-targeting (DART) molecule that combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123.

MGD006 redirects T cells to kill cells expressing CD123, which is upregulated in AML and other hematologic diseases.

Gurunadh Chichili, PhD, of MacroGenics, Inc., in Rockville, Maryland, and his colleagues described their work with MGD006 in Science Translational Medicine. MacroGenics, the company developing MGD006, funded this research.

Because MGD006 is designed to be cleared rapidly, it requires continuous delivery. So in mice, the investigators administered the molecule continuously for up to a week via peritoneally implanted osmotic pumps.

The NSG/b2m^−/− mice had been reconstituted with human peripheral blood mononuclear cells and grafted with KG-1a cells, an AML-M0 line. The mice received MGD006 after tumors were allowed to grow to an average size of about 100 mm³.

Treated mice experienced significant tumor regression at all doses of MGD006 (P<0.005), but there was no activity in mice treated with a control DART molecule. The investigators found that 500 ng/kg of MGD006 per day was sufficient to completely eliminate leukemic cells.

The team also tested MGD006 in macaques and found the molecule binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells.

The monkeys received continuous infusions of MGD006, starting at 0.1 mg/kg per day and escalating weekly to up to 1 mg/kg per day for a 4-week period. The treatment depleted circulating CD123-positive cells beginning at 72 hours and continuing throughout the infusion period.

The monkeys experienced cytokine release, but it was transient and most significant after the first dose of MDG006. After the first dose, IL-6 concentration returned to baseline by 72 hours, and the magnitude of IL-6 response decreased with each successive MGD006 infusion, even when the dose was increased.

The animals experienced reversible reductions in hematocrit and red cell mass at the highest doses of MDG006 but no neutropenia or thrombocytopenia.

“This research paved the way for our initiation of a phase 1 clinical study of MGD006 in 2014,” said Scott Koenig, MD, PhD, President and CEO of MacroGenics.

“MGD006 has demonstrated great promise as a T-cell-redirected cancer immunotherapy in preclinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome, and several other forms of leukemia and lymphoma.”

Cynomolgus monkey

Photo by Sakurai Midori

An artificial antibody that redirects T cells to target cancer cells shows promise for treating acute myeloid leukemia (AML), according to preclinical research.

The antibody, MGD006, induced tumor regression in mouse models of AML and was largely well-tolerated in cynomolgus monkeys.

Investigators say these results support clinical testing of MGD006 in AML, which is currently underway.

MGD006 is a humanized, dual-affinity re-targeting (DART) molecule that combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123.

MGD006 redirects T cells to kill cells expressing CD123, which is upregulated in AML and other hematologic diseases.

Gurunadh Chichili, PhD, of MacroGenics, Inc., in Rockville, Maryland, and his colleagues described their work with MGD006 in Science Translational Medicine. MacroGenics, the company developing MGD006, funded this research.

Because MGD006 is designed to be cleared rapidly, it requires continuous delivery. So in mice, the investigators administered the molecule continuously for up to a week via peritoneally implanted osmotic pumps.

The NSG/b2m^−/− mice had been reconstituted with human peripheral blood mononuclear cells and grafted with KG-1a cells, an AML-M0 line. The mice received MGD006 after tumors were allowed to grow to an average size of about 100 mm³.

Treated mice experienced significant tumor regression at all doses of MGD006 (P<0.005), but there was no activity in mice treated with a control DART molecule. The investigators found that 500 ng/kg of MGD006 per day was sufficient to completely eliminate leukemic cells.

The team also tested MGD006 in macaques and found the molecule binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells.

The monkeys received continuous infusions of MGD006, starting at 0.1 mg/kg per day and escalating weekly to up to 1 mg/kg per day for a 4-week period. The treatment depleted circulating CD123-positive cells beginning at 72 hours and continuing throughout the infusion period.

The monkeys experienced cytokine release, but it was transient and most significant after the first dose of MDG006. After the first dose, IL-6 concentration returned to baseline by 72 hours, and the magnitude of IL-6 response decreased with each successive MGD006 infusion, even when the dose was increased.

The animals experienced reversible reductions in hematocrit and red cell mass at the highest doses of MDG006 but no neutropenia or thrombocytopenia.

“This research paved the way for our initiation of a phase 1 clinical study of MGD006 in 2014,” said Scott Koenig, MD, PhD, President and CEO of MacroGenics.

“MGD006 has demonstrated great promise as a T-cell-redirected cancer immunotherapy in preclinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome, and several other forms of leukemia and lymphoma.”

Cynomolgus monkey

Photo by Sakurai Midori

An artificial antibody that redirects T cells to target cancer cells shows promise for treating acute myeloid leukemia (AML), according to preclinical research.

The antibody, MGD006, induced tumor regression in mouse models of AML and was largely well-tolerated in cynomolgus monkeys.

Investigators say these results support clinical testing of MGD006 in AML, which is currently underway.

MGD006 is a humanized, dual-affinity re-targeting (DART) molecule that combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123.

MGD006 redirects T cells to kill cells expressing CD123, which is upregulated in AML and other hematologic diseases.

Gurunadh Chichili, PhD, of MacroGenics, Inc., in Rockville, Maryland, and his colleagues described their work with MGD006 in Science Translational Medicine. MacroGenics, the company developing MGD006, funded this research.

Because MGD006 is designed to be cleared rapidly, it requires continuous delivery. So in mice, the investigators administered the molecule continuously for up to a week via peritoneally implanted osmotic pumps.

The NSG/b2m^−/− mice had been reconstituted with human peripheral blood mononuclear cells and grafted with KG-1a cells, an AML-M0 line. The mice received MGD006 after tumors were allowed to grow to an average size of about 100 mm³.

Treated mice experienced significant tumor regression at all doses of MGD006 (P<0.005), but there was no activity in mice treated with a control DART molecule. The investigators found that 500 ng/kg of MGD006 per day was sufficient to completely eliminate leukemic cells.

The team also tested MGD006 in macaques and found the molecule binds to human and cynomolgus monkey antigens with similar affinities and redirects T cells from either species to kill CD123-expressing target cells.

The monkeys received continuous infusions of MGD006, starting at 0.1 mg/kg per day and escalating weekly to up to 1 mg/kg per day for a 4-week period. The treatment depleted circulating CD123-positive cells beginning at 72 hours and continuing throughout the infusion period.

The monkeys experienced cytokine release, but it was transient and most significant after the first dose of MDG006. After the first dose, IL-6 concentration returned to baseline by 72 hours, and the magnitude of IL-6 response decreased with each successive MGD006 infusion, even when the dose was increased.

The animals experienced reversible reductions in hematocrit and red cell mass at the highest doses of MDG006 but no neutropenia or thrombocytopenia.

“This research paved the way for our initiation of a phase 1 clinical study of MGD006 in 2014,” said Scott Koenig, MD, PhD, President and CEO of MacroGenics.

“MGD006 has demonstrated great promise as a T-cell-redirected cancer immunotherapy in preclinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome, and several other forms of leukemia and lymphoma.”

Exposure to dexrazoxane among pediatric patients with leukemia or lymphoma did not affect overall mortality during a median follow-up period of 12.6 years, according to a report published online in the Journal of Clinical Oncology.

Aggregated data from three Children’s Oncology Group trials showed that among 1,008 pediatric patients who received treatment with doxorubicin with or without dexrazoxane (DRZ) from 1996 to 2001, exposure to DRZ was not associated with an increased risk of relapse (HR, 0.81; 95% CI, 0.60-1.08) or death (HR, 1.03; 0.73-1.45). Comparing DRZ with non-DRZ treatment groups at 10 years, the cumulative incidence of relapse was 16.1% vs. 19.1% (difference, – 3.0%; 95% CI, – 7.9% to 0.2%) and overall mortality was 12.8% vs. 12.2% (difference, – 0.6%; 95% CI, – 3.5% to 4.7%). The three trials (P9404, P9425, and P9426) evaluated individually likewise did not show significant differences in relapse or mortality rates.

Although studies in adults show a positive effect of DRZ on heart failure rates after anthracycline therapy, concern over DRZ interference with cancer therapies and a possible link to second cancers have limited its use in children and prompted Dr. Eric Chow of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues to assess the effect of DRZ on mortality.

The investigators wrote that DRZ “does not appear to interfere with cancer treatment efficacy, in terms of original cancer mortality or overall risk of relapse. Although the risk for secondary cancer mortality (mainly as a result of AML/MDS [acute myeloid leukemia/myelodysplastic syndrome]) was greater among those exposed to DRZ, the overall number of events was small, and the differences were not statistically significant,” the investigators said. (J. Clin. Oncol. 2015 May 26 [doi:10.1200/JCO.2014.59.4473])

Aggregated data from the three trials shows that the 10-year mortality rate of AML/MDS was 1.4% for those treated with DRZ (seven patients), compared with 0.8% for those treated without DRZ (five patients).

The beneficial effects of DRZ in decreasing the risk of heart failure have been observed in trials of adult patients, but the results for survivors of childhood cancers have been inconclusive because heart failure may develop over a longer time period in children. With the median age of survivors in this study of 24 years, significant differences in cardiac mortality due to DRZ use are not detectable. To evaluate DRZ as a cardioprotectant, a new Children’s Oncology Group study (Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment [HEART]) will determine the cardiovascular health of individuals in the three trials P9404, P9425, and P9426.

“Given that second cancers and symptomatic cardiac disease appear to be by far the two most common categories of serious late effects (in terms of both absolute and relative risks) among long-term childhood cancer survivors as a group … with cumulative incidences of each approaching 20% by age 50 years, any strategy that offers the promise of reduced cardiotoxicity without being offset by second cancers is highly attractive,” Dr. Chow and his associates wrote.

The study was supported by the National Institutes of Health, St. Baldrick’s Foundation, and the Leukemia and Lymphoma Society. Dr. Chow reported having no relevant financial conflicts. Three of his coauthors reported having financial relationships with industry.

Exposure to dexrazoxane among pediatric patients with leukemia or lymphoma did not affect overall mortality during a median follow-up period of 12.6 years, according to a report published online in the Journal of Clinical Oncology.

Aggregated data from three Children’s Oncology Group trials showed that among 1,008 pediatric patients who received treatment with doxorubicin with or without dexrazoxane (DRZ) from 1996 to 2001, exposure to DRZ was not associated with an increased risk of relapse (HR, 0.81; 95% CI, 0.60-1.08) or death (HR, 1.03; 0.73-1.45). Comparing DRZ with non-DRZ treatment groups at 10 years, the cumulative incidence of relapse was 16.1% vs. 19.1% (difference, – 3.0%; 95% CI, – 7.9% to 0.2%) and overall mortality was 12.8% vs. 12.2% (difference, – 0.6%; 95% CI, – 3.5% to 4.7%). The three trials (P9404, P9425, and P9426) evaluated individually likewise did not show significant differences in relapse or mortality rates.

Although studies in adults show a positive effect of DRZ on heart failure rates after anthracycline therapy, concern over DRZ interference with cancer therapies and a possible link to second cancers have limited its use in children and prompted Dr. Eric Chow of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues to assess the effect of DRZ on mortality.

The investigators wrote that DRZ “does not appear to interfere with cancer treatment efficacy, in terms of original cancer mortality or overall risk of relapse. Although the risk for secondary cancer mortality (mainly as a result of AML/MDS [acute myeloid leukemia/myelodysplastic syndrome]) was greater among those exposed to DRZ, the overall number of events was small, and the differences were not statistically significant,” the investigators said. (J. Clin. Oncol. 2015 May 26 [doi:10.1200/JCO.2014.59.4473])

Aggregated data from the three trials shows that the 10-year mortality rate of AML/MDS was 1.4% for those treated with DRZ (seven patients), compared with 0.8% for those treated without DRZ (five patients).

The beneficial effects of DRZ in decreasing the risk of heart failure have been observed in trials of adult patients, but the results for survivors of childhood cancers have been inconclusive because heart failure may develop over a longer time period in children. With the median age of survivors in this study of 24 years, significant differences in cardiac mortality due to DRZ use are not detectable. To evaluate DRZ as a cardioprotectant, a new Children’s Oncology Group study (Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment [HEART]) will determine the cardiovascular health of individuals in the three trials P9404, P9425, and P9426.

“Given that second cancers and symptomatic cardiac disease appear to be by far the two most common categories of serious late effects (in terms of both absolute and relative risks) among long-term childhood cancer survivors as a group … with cumulative incidences of each approaching 20% by age 50 years, any strategy that offers the promise of reduced cardiotoxicity without being offset by second cancers is highly attractive,” Dr. Chow and his associates wrote.

The study was supported by the National Institutes of Health, St. Baldrick’s Foundation, and the Leukemia and Lymphoma Society. Dr. Chow reported having no relevant financial conflicts. Three of his coauthors reported having financial relationships with industry.

Exposure to dexrazoxane among pediatric patients with leukemia or lymphoma did not affect overall mortality during a median follow-up period of 12.6 years, according to a report published online in the Journal of Clinical Oncology.

Aggregated data from three Children’s Oncology Group trials showed that among 1,008 pediatric patients who received treatment with doxorubicin with or without dexrazoxane (DRZ) from 1996 to 2001, exposure to DRZ was not associated with an increased risk of relapse (HR, 0.81; 95% CI, 0.60-1.08) or death (HR, 1.03; 0.73-1.45). Comparing DRZ with non-DRZ treatment groups at 10 years, the cumulative incidence of relapse was 16.1% vs. 19.1% (difference, – 3.0%; 95% CI, – 7.9% to 0.2%) and overall mortality was 12.8% vs. 12.2% (difference, – 0.6%; 95% CI, – 3.5% to 4.7%). The three trials (P9404, P9425, and P9426) evaluated individually likewise did not show significant differences in relapse or mortality rates.

Although studies in adults show a positive effect of DRZ on heart failure rates after anthracycline therapy, concern over DRZ interference with cancer therapies and a possible link to second cancers have limited its use in children and prompted Dr. Eric Chow of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues to assess the effect of DRZ on mortality.

The investigators wrote that DRZ “does not appear to interfere with cancer treatment efficacy, in terms of original cancer mortality or overall risk of relapse. Although the risk for secondary cancer mortality (mainly as a result of AML/MDS [acute myeloid leukemia/myelodysplastic syndrome]) was greater among those exposed to DRZ, the overall number of events was small, and the differences were not statistically significant,” the investigators said. (J. Clin. Oncol. 2015 May 26 [doi:10.1200/JCO.2014.59.4473])

Aggregated data from the three trials shows that the 10-year mortality rate of AML/MDS was 1.4% for those treated with DRZ (seven patients), compared with 0.8% for those treated without DRZ (five patients).

The beneficial effects of DRZ in decreasing the risk of heart failure have been observed in trials of adult patients, but the results for survivors of childhood cancers have been inconclusive because heart failure may develop over a longer time period in children. With the median age of survivors in this study of 24 years, significant differences in cardiac mortality due to DRZ use are not detectable. To evaluate DRZ as a cardioprotectant, a new Children’s Oncology Group study (Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment [HEART]) will determine the cardiovascular health of individuals in the three trials P9404, P9425, and P9426.

“Given that second cancers and symptomatic cardiac disease appear to be by far the two most common categories of serious late effects (in terms of both absolute and relative risks) among long-term childhood cancer survivors as a group … with cumulative incidences of each approaching 20% by age 50 years, any strategy that offers the promise of reduced cardiotoxicity without being offset by second cancers is highly attractive,” Dr. Chow and his associates wrote.

The study was supported by the National Institutes of Health, St. Baldrick’s Foundation, and the Leukemia and Lymphoma Society. Dr. Chow reported having no relevant financial conflicts. Three of his coauthors reported having financial relationships with industry.