Leukemia, Myelodysplasia, Transplantation

Micrograph showing MDS

A 3-arm phase 2 study of azacitidine alone or in combination with lenalidomide or vorinostat in patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) has shown the combination therapies to have similar overall response rates (ORR) to azacitidine monotherapy. Based on these findings, investigators did not choose either combination arm for phase 3 testing of overall survival.

However, patients with CMML treated with the azacitidine-lenalidomide combination had twice the ORR compared with azacitidine monotherapy, they reported.

And patients with certain mutations, such as DNMT3A, BCOR, and NRAS, had higher overall response rates, although only those with the DNMT3A mutation were significant.

Mikkael A. Sekeres, MD, of the Cleveland Clinic in Cleveland, Ohio, and colleagues reported these findings in the Journal of Clinical Oncology on behalf of the North American Intergroup Study SWOG S117.

Doses of azacitidine were the same for monotherapy and combination arms: 75 mg/m²/day intravenously or subcutaneously on days 1 to 7 of a 28-day cycle.

Patients in the lenalidomide arm received 10 mg/day orally of that drug on days 1 to 21, and patients in the vorinostat arm received 300 mg twice daily orally on days 3 to 9.

Patient characteristics

Patients had MDS of IPSS Intermediate-2 or higher or bone marrow blasts 5% or greater. Patients with CMML had fewer than 20% blasts.

The investigators randomized 277 patients to receive either azacitidine alone (n=92), azacitidine plus lenalidomide (n=93), or azacitidine plus vorinostat (n=92).

 Patients were a median age of 70 years (range, 28 to 93). Eighty-five patients (31%) were female, 53 (19%) had CMML, and 18 (6%) had treatment-related MDS. More than half the patients were transfusion-dependent at baseline.

Baseline characteristics were similar across the 3 arms. The investigators noted that the baseline characteristics were also similar across the 90 centers participating in the study, whether they were an MDS Center of Excellence or a high-volume center.

Adverse events

 For the most part, therapy-related adverse events were similar across the arms.

Rates of grade 3 or higher febrile neutropenia and infection and infestations were similar for all 3 cohorts: 89% for azaciditine monotherapy, 91% for the lenalidomide combination, and 91% for the vorinostat combination.

However, the vorinostat arm had more grade 3 or higher gastrointestinal toxicities (14 patients, 15%) compared with the monotherapy arm (4 patients, 4%), P=0.02.

And patients receiving lenalidomide experienced more grade 3 or higher rash (14 patients, 16%) compared with patients receiving monotherapy (3 patients, 3%), P=0.005.

Patients in the combination arms stopped therapy at significantly higher rates than the monotherapy arm. Eight percent of patients receiving monotherapy stopped treatment compared with 20% in the lenalidomide arm and 21% in the vorinostat arm.

Patients in the combination arms also had more dose modifications not specified in the protocol than those in the monotherapy arm. Twenty-four percent receiving azacitidine monotherapy had non-protocol defined dose modifications, compared with 43% in the lenalidomide arm and 42% in the vorinostat arm.

Responses

The ORR for the entire study population was 38%.

Patients in the monotherapy arm had an ORR of 38%, those in the lenalidomide arm, 49%, and those in the vorinostate arm, 27%. Neither arm achieved significance compared with the monotherapy arm.

Patients who were treatment-naïve in the lenalidomide arm had a somewhat improved ORR compared with monotherapy, P=0.08.

The median duration of response for all cohorts was 15 months: 10 months for monotherapy, 14 months for lenalidomide, and 18 months for vorinostat.

Patients who were able to remain on therapy for 6 months or more in the lenalidomide arm achieved a higher ORR of 87% compared with monotherapy (62%, P=0.01). However, there was no difference in response duration with longer therapy.

 

The median overall survival (OS) was 17 months for all patients, 15 months for patients in the monotherapy group, 19 months for those in the lenalidomide arm, and 17 months for those in the vorinostat group.

CMML patients had similar OS across treatment arms, with the median not yet reached for patients in the monotherapy arm.

Subgroup responses

Patients with CMML in the lenalidomide arm had a significantly higher ORR than CMML patients in the monotherapy arm, 68% and 28%, respectively (P=0.02).

Median duration of response for CMML patients was 19 months, with no differences between the arms.

The investigators observed no differences in ORR for therapy-related MDS, IPSS subgroups, transfusion-dependent patients, or allogeneic transplant rates.

However, they noted ORR was better for patients with chromosome 5 abnormality regardless of treatment arm than for those without the abnormality (odds ratio, 2.17, P=0.008).

One hundred thirteen patients had mutational data available. They had a median number of 2 mutations (range, 0 to 7), with the most common being ASXL1 (n = 31), TET2 (n = 26), SRSF2 (n = 23), TP53 (n = 22), RUNX1 (n = 21), and U2AF1 (n = 19).

Patients with DNMT3A mutation had a significantly higher ORR than for patients without mutations, 67% and 34%, respectively P=0.025).

Patients with BCOR and NRAS mutations had numerically higher, but non-significant, ORR than non-mutated patients. Patients with BCOR mutation had a 57% ORR compared with 34% for non-mutated patients (P=0.23).  Patients with NRAS mutation had a 60% ORR compared with 36% for non-mutated patients (P=0.28).

Patients with mutations in TET2 (P = .046) and TP53 (P = .003) had a worse response duration than those without mutations.

Response duration was significantly better with fewer mutations. For 2 or more mutations, the hazard ration was 6.86 versus no mutations (P=0.01).

The investigators believed under-dosing may have compromised response and survival in the combination arms. They suggested that studies focused on the subgroups that seemed to benefit from the combinations should be conducted. 

Micrograph showing MDS

A 3-arm phase 2 study of azacitidine alone or in combination with lenalidomide or vorinostat in patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) has shown the combination therapies to have similar overall response rates (ORR) to azacitidine monotherapy. Based on these findings, investigators did not choose either combination arm for phase 3 testing of overall survival.

However, patients with CMML treated with the azacitidine-lenalidomide combination had twice the ORR compared with azacitidine monotherapy, they reported.

And patients with certain mutations, such as DNMT3A, BCOR, and NRAS, had higher overall response rates, although only those with the DNMT3A mutation were significant.

Mikkael A. Sekeres, MD, of the Cleveland Clinic in Cleveland, Ohio, and colleagues reported these findings in the Journal of Clinical Oncology on behalf of the North American Intergroup Study SWOG S117.

Doses of azacitidine were the same for monotherapy and combination arms: 75 mg/m²/day intravenously or subcutaneously on days 1 to 7 of a 28-day cycle.

Patients in the lenalidomide arm received 10 mg/day orally of that drug on days 1 to 21, and patients in the vorinostat arm received 300 mg twice daily orally on days 3 to 9.

Patient characteristics

Patients had MDS of IPSS Intermediate-2 or higher or bone marrow blasts 5% or greater. Patients with CMML had fewer than 20% blasts.

The investigators randomized 277 patients to receive either azacitidine alone (n=92), azacitidine plus lenalidomide (n=93), or azacitidine plus vorinostat (n=92).

 Patients were a median age of 70 years (range, 28 to 93). Eighty-five patients (31%) were female, 53 (19%) had CMML, and 18 (6%) had treatment-related MDS. More than half the patients were transfusion-dependent at baseline.

Baseline characteristics were similar across the 3 arms. The investigators noted that the baseline characteristics were also similar across the 90 centers participating in the study, whether they were an MDS Center of Excellence or a high-volume center.

Adverse events

 For the most part, therapy-related adverse events were similar across the arms.

Rates of grade 3 or higher febrile neutropenia and infection and infestations were similar for all 3 cohorts: 89% for azaciditine monotherapy, 91% for the lenalidomide combination, and 91% for the vorinostat combination.

However, the vorinostat arm had more grade 3 or higher gastrointestinal toxicities (14 patients, 15%) compared with the monotherapy arm (4 patients, 4%), P=0.02.

And patients receiving lenalidomide experienced more grade 3 or higher rash (14 patients, 16%) compared with patients receiving monotherapy (3 patients, 3%), P=0.005.

Patients in the combination arms stopped therapy at significantly higher rates than the monotherapy arm. Eight percent of patients receiving monotherapy stopped treatment compared with 20% in the lenalidomide arm and 21% in the vorinostat arm.

Patients in the combination arms also had more dose modifications not specified in the protocol than those in the monotherapy arm. Twenty-four percent receiving azacitidine monotherapy had non-protocol defined dose modifications, compared with 43% in the lenalidomide arm and 42% in the vorinostat arm.

Responses

The ORR for the entire study population was 38%.

Patients in the monotherapy arm had an ORR of 38%, those in the lenalidomide arm, 49%, and those in the vorinostate arm, 27%. Neither arm achieved significance compared with the monotherapy arm.

Patients who were treatment-naïve in the lenalidomide arm had a somewhat improved ORR compared with monotherapy, P=0.08.

The median duration of response for all cohorts was 15 months: 10 months for monotherapy, 14 months for lenalidomide, and 18 months for vorinostat.

Patients who were able to remain on therapy for 6 months or more in the lenalidomide arm achieved a higher ORR of 87% compared with monotherapy (62%, P=0.01). However, there was no difference in response duration with longer therapy.

 

The median overall survival (OS) was 17 months for all patients, 15 months for patients in the monotherapy group, 19 months for those in the lenalidomide arm, and 17 months for those in the vorinostat group.

CMML patients had similar OS across treatment arms, with the median not yet reached for patients in the monotherapy arm.

Subgroup responses

Patients with CMML in the lenalidomide arm had a significantly higher ORR than CMML patients in the monotherapy arm, 68% and 28%, respectively (P=0.02).

Median duration of response for CMML patients was 19 months, with no differences between the arms.

The investigators observed no differences in ORR for therapy-related MDS, IPSS subgroups, transfusion-dependent patients, or allogeneic transplant rates.

However, they noted ORR was better for patients with chromosome 5 abnormality regardless of treatment arm than for those without the abnormality (odds ratio, 2.17, P=0.008).

One hundred thirteen patients had mutational data available. They had a median number of 2 mutations (range, 0 to 7), with the most common being ASXL1 (n = 31), TET2 (n = 26), SRSF2 (n = 23), TP53 (n = 22), RUNX1 (n = 21), and U2AF1 (n = 19).

Patients with DNMT3A mutation had a significantly higher ORR than for patients without mutations, 67% and 34%, respectively P=0.025).

Patients with BCOR and NRAS mutations had numerically higher, but non-significant, ORR than non-mutated patients. Patients with BCOR mutation had a 57% ORR compared with 34% for non-mutated patients (P=0.23).  Patients with NRAS mutation had a 60% ORR compared with 36% for non-mutated patients (P=0.28).

Patients with mutations in TET2 (P = .046) and TP53 (P = .003) had a worse response duration than those without mutations.

Response duration was significantly better with fewer mutations. For 2 or more mutations, the hazard ration was 6.86 versus no mutations (P=0.01).

The investigators believed under-dosing may have compromised response and survival in the combination arms. They suggested that studies focused on the subgroups that seemed to benefit from the combinations should be conducted. 

Micrograph showing MDS

A 3-arm phase 2 study of azacitidine alone or in combination with lenalidomide or vorinostat in patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) has shown the combination therapies to have similar overall response rates (ORR) to azacitidine monotherapy. Based on these findings, investigators did not choose either combination arm for phase 3 testing of overall survival.

However, patients with CMML treated with the azacitidine-lenalidomide combination had twice the ORR compared with azacitidine monotherapy, they reported.

And patients with certain mutations, such as DNMT3A, BCOR, and NRAS, had higher overall response rates, although only those with the DNMT3A mutation were significant.

Mikkael A. Sekeres, MD, of the Cleveland Clinic in Cleveland, Ohio, and colleagues reported these findings in the Journal of Clinical Oncology on behalf of the North American Intergroup Study SWOG S117.

Doses of azacitidine were the same for monotherapy and combination arms: 75 mg/m²/day intravenously or subcutaneously on days 1 to 7 of a 28-day cycle.

Patients in the lenalidomide arm received 10 mg/day orally of that drug on days 1 to 21, and patients in the vorinostat arm received 300 mg twice daily orally on days 3 to 9.

Patient characteristics

Patients had MDS of IPSS Intermediate-2 or higher or bone marrow blasts 5% or greater. Patients with CMML had fewer than 20% blasts.

The investigators randomized 277 patients to receive either azacitidine alone (n=92), azacitidine plus lenalidomide (n=93), or azacitidine plus vorinostat (n=92).

 Patients were a median age of 70 years (range, 28 to 93). Eighty-five patients (31%) were female, 53 (19%) had CMML, and 18 (6%) had treatment-related MDS. More than half the patients were transfusion-dependent at baseline.

Baseline characteristics were similar across the 3 arms. The investigators noted that the baseline characteristics were also similar across the 90 centers participating in the study, whether they were an MDS Center of Excellence or a high-volume center.

Adverse events

 For the most part, therapy-related adverse events were similar across the arms.

Rates of grade 3 or higher febrile neutropenia and infection and infestations were similar for all 3 cohorts: 89% for azaciditine monotherapy, 91% for the lenalidomide combination, and 91% for the vorinostat combination.

However, the vorinostat arm had more grade 3 or higher gastrointestinal toxicities (14 patients, 15%) compared with the monotherapy arm (4 patients, 4%), P=0.02.

And patients receiving lenalidomide experienced more grade 3 or higher rash (14 patients, 16%) compared with patients receiving monotherapy (3 patients, 3%), P=0.005.

Patients in the combination arms stopped therapy at significantly higher rates than the monotherapy arm. Eight percent of patients receiving monotherapy stopped treatment compared with 20% in the lenalidomide arm and 21% in the vorinostat arm.

Patients in the combination arms also had more dose modifications not specified in the protocol than those in the monotherapy arm. Twenty-four percent receiving azacitidine monotherapy had non-protocol defined dose modifications, compared with 43% in the lenalidomide arm and 42% in the vorinostat arm.

Responses

The ORR for the entire study population was 38%.

Patients in the monotherapy arm had an ORR of 38%, those in the lenalidomide arm, 49%, and those in the vorinostate arm, 27%. Neither arm achieved significance compared with the monotherapy arm.

Patients who were treatment-naïve in the lenalidomide arm had a somewhat improved ORR compared with monotherapy, P=0.08.

The median duration of response for all cohorts was 15 months: 10 months for monotherapy, 14 months for lenalidomide, and 18 months for vorinostat.

Patients who were able to remain on therapy for 6 months or more in the lenalidomide arm achieved a higher ORR of 87% compared with monotherapy (62%, P=0.01). However, there was no difference in response duration with longer therapy.

 

The median overall survival (OS) was 17 months for all patients, 15 months for patients in the monotherapy group, 19 months for those in the lenalidomide arm, and 17 months for those in the vorinostat group.

CMML patients had similar OS across treatment arms, with the median not yet reached for patients in the monotherapy arm.

Subgroup responses

Patients with CMML in the lenalidomide arm had a significantly higher ORR than CMML patients in the monotherapy arm, 68% and 28%, respectively (P=0.02).

Median duration of response for CMML patients was 19 months, with no differences between the arms.

The investigators observed no differences in ORR for therapy-related MDS, IPSS subgroups, transfusion-dependent patients, or allogeneic transplant rates.

However, they noted ORR was better for patients with chromosome 5 abnormality regardless of treatment arm than for those without the abnormality (odds ratio, 2.17, P=0.008).

One hundred thirteen patients had mutational data available. They had a median number of 2 mutations (range, 0 to 7), with the most common being ASXL1 (n = 31), TET2 (n = 26), SRSF2 (n = 23), TP53 (n = 22), RUNX1 (n = 21), and U2AF1 (n = 19).

Patients with DNMT3A mutation had a significantly higher ORR than for patients without mutations, 67% and 34%, respectively P=0.025).

Patients with BCOR and NRAS mutations had numerically higher, but non-significant, ORR than non-mutated patients. Patients with BCOR mutation had a 57% ORR compared with 34% for non-mutated patients (P=0.23).  Patients with NRAS mutation had a 60% ORR compared with 36% for non-mutated patients (P=0.28).

Patients with mutations in TET2 (P = .046) and TP53 (P = .003) had a worse response duration than those without mutations.

Response duration was significantly better with fewer mutations. For 2 or more mutations, the hazard ration was 6.86 versus no mutations (P=0.01).

The investigators believed under-dosing may have compromised response and survival in the combination arms. They suggested that studies focused on the subgroups that seemed to benefit from the combinations should be conducted. 

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo courtesy of the CDC

A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4^th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.

The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.

The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.

For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.

In the treatment of FN, the panel added a 4^th-generation cephalosporin as empirical therapy in high-risk FN.

The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.

The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients.  GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.

The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.

Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.

The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.

The panel's recommendations and their rationale can be found in the JCO article.

The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.

Photo courtesy of the CDC

A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4^th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.

The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.

The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.

For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.

In the treatment of FN, the panel added a 4^th-generation cephalosporin as empirical therapy in high-risk FN.

The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.

The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients.  GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.

The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.

Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.

The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.

The panel's recommendations and their rationale can be found in the JCO article.

The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.

Photo courtesy of the CDC

A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4^th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.

The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.

The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.

For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.

In the treatment of FN, the panel added a 4^th-generation cephalosporin as empirical therapy in high-risk FN.

The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.

The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients.  GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.

The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.

Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.

The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.

The panel's recommendations and their rationale can be found in the JCO article.

The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.

Winship Cancer Institute

Physician, researcher, and educator H. Jean Khoury, MD, recently passed away.

He died on Monday, May 22, at the age of 50, after a year-long battle with esophageal cancer.

Dr Khoury led the division of hematology at Winship Cancer Institute of Emory University in Atlanta, Georgia.

He was considered an authority on hematologic malignancies, particularly chronic myeloid leukemia (CML), acute leukemia, and myelodysplastic syndromes (MDS).

Dr Khoury joined Winship Cancer Institute in 2004 as director of the Leukemia Service and associate professor in the Emory School of Medicine.

In 2009, he was promoted to professor and director of the Division of Hematology in the Department of Hematology and Medical Oncology, and he was later named to the R. Randall Rollins Chair in Oncology.

“We are all deeply grieving the loss of this remarkable man who gave so much to Winship,” said Walter J. Curran, Jr, MD, Winship Cancer Institute’s executive director.

“His enthusiasm and love for his patients and his commitment to lessening the burden of cancer for all has been unwavering throughout his life.”

A native of Beirut, Lebanon, Dr Khoury came to the Winship Cancer Institute from Washington University in St Louis, Missouri, where he served on the faculty after completing a fellowship in hematology-oncology.

He earned his medical degree from the Université Catholique de Louvain in Brussels, Belgium, and completed a residency in internal medicine at Memorial Medical Center in Savannah, Georgia.

Dr Khoury was recruited to Winship Cancer Institute by Fadlo R. Khuri, MD, former deputy director of the institute and now president of the American University of Beirut. What he first saw in Dr Khoury was someone who was “in the best sense, a disruptive presence.”

“What you always want in a leader is someone who’s not afraid to be wrong, to take risks,” Dr Khuri said. “Being wrong disrupts the pattern, and Jean was very brave. He didn’t like business as usual, and that showed in the way he took about redeveloping the hematology division, the leukemia program, and his interactions with the transplant division, with faculty, and all across Winship.”

According to his colleagues, Dr Khoury’s guiding principle was how to improve his patients’ lives, whether through research discoveries or through compassionate care.

Even after being diagnosed with cancer himself, Dr Khoury continued to see patients and carry on his work in the clinic and his research.

Dr Khoury pioneered the development of personalized treatment for CML patients and better approaches to improve quality of life for survivors. His research focused on drug development in leukemia and MDS, genomic abnormalities in leukemia, development of cost-effective practice models, and outcome analysis of bone marrow transplant.

He conducted several leukemia and transplant clinical trials, including trials that led to the approval of drugs such as imatinib, dasatinib, and nilotinib.

Dr Khoury received the Georgia Cancer Coalition Distinguished Cancer Scholarship, which allowed for establishment of the Hematological Disorders Tissue Bank at Emory, which now contains annotated germline and somatic samples from more than 800 patients with various hematologic disorders.

Dr Khoury died at home with his family by his side. He is survived by his wife, Angela, and 3 children, Mikhail, Iman, and Alya.

In lieu of flowers, the family requests that contributions be made to a new fund at Winship Cancer Institute that will memorialize the life and work of Dr Khoury by supporting a fellowship program that was so meaningful to him.

Contributions, marked in Memory of Dr H. Jean Khoury, can be sent to Winship Cancer Institute of Emory University, Office of Gift Records, Emory University, 1762 Clifton Rd. NE, Suite 1400, Atlanta, GA 30322. Gifts can also be made online.

 

There will be a memorial service for Dr Khoury on Wednesday, May 31, at 4:30 pm at Glenn Memorial Church, 1652 North Decatur Road in Atlanta, Georgia. 

Winship Cancer Institute

Physician, researcher, and educator H. Jean Khoury, MD, recently passed away.

He died on Monday, May 22, at the age of 50, after a year-long battle with esophageal cancer.

Dr Khoury led the division of hematology at Winship Cancer Institute of Emory University in Atlanta, Georgia.

He was considered an authority on hematologic malignancies, particularly chronic myeloid leukemia (CML), acute leukemia, and myelodysplastic syndromes (MDS).

Dr Khoury joined Winship Cancer Institute in 2004 as director of the Leukemia Service and associate professor in the Emory School of Medicine.

In 2009, he was promoted to professor and director of the Division of Hematology in the Department of Hematology and Medical Oncology, and he was later named to the R. Randall Rollins Chair in Oncology.

“We are all deeply grieving the loss of this remarkable man who gave so much to Winship,” said Walter J. Curran, Jr, MD, Winship Cancer Institute’s executive director.

“His enthusiasm and love for his patients and his commitment to lessening the burden of cancer for all has been unwavering throughout his life.”

A native of Beirut, Lebanon, Dr Khoury came to the Winship Cancer Institute from Washington University in St Louis, Missouri, where he served on the faculty after completing a fellowship in hematology-oncology.

He earned his medical degree from the Université Catholique de Louvain in Brussels, Belgium, and completed a residency in internal medicine at Memorial Medical Center in Savannah, Georgia.

Dr Khoury was recruited to Winship Cancer Institute by Fadlo R. Khuri, MD, former deputy director of the institute and now president of the American University of Beirut. What he first saw in Dr Khoury was someone who was “in the best sense, a disruptive presence.”

“What you always want in a leader is someone who’s not afraid to be wrong, to take risks,” Dr Khuri said. “Being wrong disrupts the pattern, and Jean was very brave. He didn’t like business as usual, and that showed in the way he took about redeveloping the hematology division, the leukemia program, and his interactions with the transplant division, with faculty, and all across Winship.”

According to his colleagues, Dr Khoury’s guiding principle was how to improve his patients’ lives, whether through research discoveries or through compassionate care.

Even after being diagnosed with cancer himself, Dr Khoury continued to see patients and carry on his work in the clinic and his research.

Dr Khoury pioneered the development of personalized treatment for CML patients and better approaches to improve quality of life for survivors. His research focused on drug development in leukemia and MDS, genomic abnormalities in leukemia, development of cost-effective practice models, and outcome analysis of bone marrow transplant.

He conducted several leukemia and transplant clinical trials, including trials that led to the approval of drugs such as imatinib, dasatinib, and nilotinib.

Dr Khoury received the Georgia Cancer Coalition Distinguished Cancer Scholarship, which allowed for establishment of the Hematological Disorders Tissue Bank at Emory, which now contains annotated germline and somatic samples from more than 800 patients with various hematologic disorders.

Dr Khoury died at home with his family by his side. He is survived by his wife, Angela, and 3 children, Mikhail, Iman, and Alya.

In lieu of flowers, the family requests that contributions be made to a new fund at Winship Cancer Institute that will memorialize the life and work of Dr Khoury by supporting a fellowship program that was so meaningful to him.

Contributions, marked in Memory of Dr H. Jean Khoury, can be sent to Winship Cancer Institute of Emory University, Office of Gift Records, Emory University, 1762 Clifton Rd. NE, Suite 1400, Atlanta, GA 30322. Gifts can also be made online.

 

There will be a memorial service for Dr Khoury on Wednesday, May 31, at 4:30 pm at Glenn Memorial Church, 1652 North Decatur Road in Atlanta, Georgia. 

Winship Cancer Institute

Physician, researcher, and educator H. Jean Khoury, MD, recently passed away.

He died on Monday, May 22, at the age of 50, after a year-long battle with esophageal cancer.

Dr Khoury led the division of hematology at Winship Cancer Institute of Emory University in Atlanta, Georgia.

He was considered an authority on hematologic malignancies, particularly chronic myeloid leukemia (CML), acute leukemia, and myelodysplastic syndromes (MDS).

Dr Khoury joined Winship Cancer Institute in 2004 as director of the Leukemia Service and associate professor in the Emory School of Medicine.

In 2009, he was promoted to professor and director of the Division of Hematology in the Department of Hematology and Medical Oncology, and he was later named to the R. Randall Rollins Chair in Oncology.

“We are all deeply grieving the loss of this remarkable man who gave so much to Winship,” said Walter J. Curran, Jr, MD, Winship Cancer Institute’s executive director.

“His enthusiasm and love for his patients and his commitment to lessening the burden of cancer for all has been unwavering throughout his life.”

A native of Beirut, Lebanon, Dr Khoury came to the Winship Cancer Institute from Washington University in St Louis, Missouri, where he served on the faculty after completing a fellowship in hematology-oncology.

He earned his medical degree from the Université Catholique de Louvain in Brussels, Belgium, and completed a residency in internal medicine at Memorial Medical Center in Savannah, Georgia.

Dr Khoury was recruited to Winship Cancer Institute by Fadlo R. Khuri, MD, former deputy director of the institute and now president of the American University of Beirut. What he first saw in Dr Khoury was someone who was “in the best sense, a disruptive presence.”

“What you always want in a leader is someone who’s not afraid to be wrong, to take risks,” Dr Khuri said. “Being wrong disrupts the pattern, and Jean was very brave. He didn’t like business as usual, and that showed in the way he took about redeveloping the hematology division, the leukemia program, and his interactions with the transplant division, with faculty, and all across Winship.”

According to his colleagues, Dr Khoury’s guiding principle was how to improve his patients’ lives, whether through research discoveries or through compassionate care.

Even after being diagnosed with cancer himself, Dr Khoury continued to see patients and carry on his work in the clinic and his research.

Dr Khoury pioneered the development of personalized treatment for CML patients and better approaches to improve quality of life for survivors. His research focused on drug development in leukemia and MDS, genomic abnormalities in leukemia, development of cost-effective practice models, and outcome analysis of bone marrow transplant.

He conducted several leukemia and transplant clinical trials, including trials that led to the approval of drugs such as imatinib, dasatinib, and nilotinib.

Dr Khoury received the Georgia Cancer Coalition Distinguished Cancer Scholarship, which allowed for establishment of the Hematological Disorders Tissue Bank at Emory, which now contains annotated germline and somatic samples from more than 800 patients with various hematologic disorders.

Dr Khoury died at home with his family by his side. He is survived by his wife, Angela, and 3 children, Mikhail, Iman, and Alya.

In lieu of flowers, the family requests that contributions be made to a new fund at Winship Cancer Institute that will memorialize the life and work of Dr Khoury by supporting a fellowship program that was so meaningful to him.

Contributions, marked in Memory of Dr H. Jean Khoury, can be sent to Winship Cancer Institute of Emory University, Office of Gift Records, Emory University, 1762 Clifton Rd. NE, Suite 1400, Atlanta, GA 30322. Gifts can also be made online.

 

There will be a memorial service for Dr Khoury on Wednesday, May 31, at 4:30 pm at Glenn Memorial Church, 1652 North Decatur Road in Atlanta, Georgia. 

 

NEW YORK – Three courses of treatment with the novel combination of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) was well tolerated and associated with a high rate of minimal residual disease (MRD)–negative remission in the bone marrow of favorable-risk, treatment-naive patients with chronic lymphocytic leukemia, based on early results from an ongoing investigator-initiated phase II trial.

Of 29 patients, 24 had completed treatment and been followed for a median of 8.3 months. All 24 had an overall response rate (42% complete response/complete remission with incomplete blood count recovery and 58% partial response), and 83% of patients achieved MRD negativity (100% with complete response and 71% with partial response), Nitin Jain, MD, reported at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

“It appears that the MRD-negativity rate continues to improve over time,” Dr. Jain of MD Anderson Cancer Center, Houston, reported. The MRD-negativity rate increased to 89% at 6 months, and 100% at 9 and 12 months.

All nine patients who reached the 12-month time point are off therapy and are being monitored, he said.

Patients with IGHV mutations generally have favorable long-term outcomes with 10-year progression-free survival rates greater than 60% after receiving standard first-line therapy with fludarabine, cyclophosphamide, and rituximab (FCR). However, ibrutinib is approved for patients with CLL, and obinutuzumab, a glycoengineered type II CD20 monoclonal antibody, was superior to rituximab in the CLL11 trial, Dr. Jain said.

Further, data from the HELIOS trial indicated that combining targeted therapies with chemoimmunotherapy is safe and effective.

iFCG was developed with the intent to limit fludarabine and cyclophosphamide to three courses, potentially reducing short- and long-term toxicity, while maintaining efficacy through the addition of ibrutinib and obinutuzumab, he explained.

Of note, higher pretreatment levels of beta-2 microglobulin were associated with a lower MRD-negativity rate after 3 cycles of iFCG, he said.

In six patients with beta-2 microglobulin of 4 mg/dL or greater, the rate was 50%, compared with 94% in 18 patients with beta-2 microglobulin less than 4 mg/dL.

The patients in the current analysis had a median age of 60 years and adequate organ function. All had IGHV mutation and did not have del(17p) or TP53 mutation. They received three courses of iFCG, including ibrutinib at 420 mg once daily continuously starting at day 1 of course 1 (C1D1); obinutuzumab at 100 mg C1D1, 900 mg C1D2, 1000 mg C1D8, 1000 mg C1D15, 1000 mg C2D1, and 1000 mg C3D1; fludarabine at 25 mg/m² daily for 3 days each course; and cyclophosphamide at 250mg/m² daily for 3 days each course.

Per study protocol, all patients receive ibrutinib with obinutuzumab for courses 4-6. Patients meeting the primary endpoint of complete response/complete remission with incomplete blood count recovery and bone marrow MRD negativity received ibrutinib monotherapy for courses 7-12. Those who did not achieve the primary endpoint received six more courses of ibrutinib and obinutuzumab. All patients who are MRD negative at 1 year stop all therapy, including ibrutinib, while those who are MRD positive at 1 year may continue ibrutinib monotherapy until disease progression.

The target bone marrow MRD-negative rate after 3 cycles of iFCG is 45%. The historic C3 bone marrow MRD-negative rate with standard FCR therapy in patients with IGHV mutation is 26%, Dr. Jain said, noting that the rate in the current analysis compared favorably with both.

The treatment thus far has been generally well tolerated. Toxicities included neutropenia (grade 3 and 4 occurring in 9 and 12 patients, respectively), thrombocytopenia (grade 3 and 4 occurring in 12 and 1 patients, respectively), ALT/AST (grade 3 and 4 occurring in 3 and 1 patients respectively), atrial fibrillation (grade 3 occurring in 1 patient), arthralgia (grade 3 occurring in 1 patient), and infusion-related reaction (grade 2 and 3 occurring in 9 patients and 1 patient, respectively).

Infections included herpes zoster, acute cholecystitis, pulmonary mycobacterium avium complex infection, and pneumocystis pneumonia, which occurred in 1 patient each, and neutropenic fever, which occurred in 4 patients.

“Notably, no patient has progressed or died in the study so far,” Dr. Jain said.

The trial continues to enroll patients, with plans for enrolling a total of 45.

Dr. Jain has received research support from and/or served on an advisory board for Pharmacyclics, Genentech, Abbvie, Prizer, Incyte, BMS, Infinity, ADC Therapeutics, Seattle Genetics, Celgene, Servier, Novartis Novimmune, and Adaptive Biotechnologies.

[email protected]

 

NEW YORK – Three courses of treatment with the novel combination of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) was well tolerated and associated with a high rate of minimal residual disease (MRD)–negative remission in the bone marrow of favorable-risk, treatment-naive patients with chronic lymphocytic leukemia, based on early results from an ongoing investigator-initiated phase II trial.

Of 29 patients, 24 had completed treatment and been followed for a median of 8.3 months. All 24 had an overall response rate (42% complete response/complete remission with incomplete blood count recovery and 58% partial response), and 83% of patients achieved MRD negativity (100% with complete response and 71% with partial response), Nitin Jain, MD, reported at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

“It appears that the MRD-negativity rate continues to improve over time,” Dr. Jain of MD Anderson Cancer Center, Houston, reported. The MRD-negativity rate increased to 89% at 6 months, and 100% at 9 and 12 months.

All nine patients who reached the 12-month time point are off therapy and are being monitored, he said.

Patients with IGHV mutations generally have favorable long-term outcomes with 10-year progression-free survival rates greater than 60% after receiving standard first-line therapy with fludarabine, cyclophosphamide, and rituximab (FCR). However, ibrutinib is approved for patients with CLL, and obinutuzumab, a glycoengineered type II CD20 monoclonal antibody, was superior to rituximab in the CLL11 trial, Dr. Jain said.

Further, data from the HELIOS trial indicated that combining targeted therapies with chemoimmunotherapy is safe and effective.

iFCG was developed with the intent to limit fludarabine and cyclophosphamide to three courses, potentially reducing short- and long-term toxicity, while maintaining efficacy through the addition of ibrutinib and obinutuzumab, he explained.

Of note, higher pretreatment levels of beta-2 microglobulin were associated with a lower MRD-negativity rate after 3 cycles of iFCG, he said.

In six patients with beta-2 microglobulin of 4 mg/dL or greater, the rate was 50%, compared with 94% in 18 patients with beta-2 microglobulin less than 4 mg/dL.

The patients in the current analysis had a median age of 60 years and adequate organ function. All had IGHV mutation and did not have del(17p) or TP53 mutation. They received three courses of iFCG, including ibrutinib at 420 mg once daily continuously starting at day 1 of course 1 (C1D1); obinutuzumab at 100 mg C1D1, 900 mg C1D2, 1000 mg C1D8, 1000 mg C1D15, 1000 mg C2D1, and 1000 mg C3D1; fludarabine at 25 mg/m² daily for 3 days each course; and cyclophosphamide at 250mg/m² daily for 3 days each course.

Per study protocol, all patients receive ibrutinib with obinutuzumab for courses 4-6. Patients meeting the primary endpoint of complete response/complete remission with incomplete blood count recovery and bone marrow MRD negativity received ibrutinib monotherapy for courses 7-12. Those who did not achieve the primary endpoint received six more courses of ibrutinib and obinutuzumab. All patients who are MRD negative at 1 year stop all therapy, including ibrutinib, while those who are MRD positive at 1 year may continue ibrutinib monotherapy until disease progression.

The target bone marrow MRD-negative rate after 3 cycles of iFCG is 45%. The historic C3 bone marrow MRD-negative rate with standard FCR therapy in patients with IGHV mutation is 26%, Dr. Jain said, noting that the rate in the current analysis compared favorably with both.

The treatment thus far has been generally well tolerated. Toxicities included neutropenia (grade 3 and 4 occurring in 9 and 12 patients, respectively), thrombocytopenia (grade 3 and 4 occurring in 12 and 1 patients, respectively), ALT/AST (grade 3 and 4 occurring in 3 and 1 patients respectively), atrial fibrillation (grade 3 occurring in 1 patient), arthralgia (grade 3 occurring in 1 patient), and infusion-related reaction (grade 2 and 3 occurring in 9 patients and 1 patient, respectively).

Infections included herpes zoster, acute cholecystitis, pulmonary mycobacterium avium complex infection, and pneumocystis pneumonia, which occurred in 1 patient each, and neutropenic fever, which occurred in 4 patients.

“Notably, no patient has progressed or died in the study so far,” Dr. Jain said.

The trial continues to enroll patients, with plans for enrolling a total of 45.

Dr. Jain has received research support from and/or served on an advisory board for Pharmacyclics, Genentech, Abbvie, Prizer, Incyte, BMS, Infinity, ADC Therapeutics, Seattle Genetics, Celgene, Servier, Novartis Novimmune, and Adaptive Biotechnologies.

[email protected]

 

NEW YORK – Three courses of treatment with the novel combination of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) was well tolerated and associated with a high rate of minimal residual disease (MRD)–negative remission in the bone marrow of favorable-risk, treatment-naive patients with chronic lymphocytic leukemia, based on early results from an ongoing investigator-initiated phase II trial.

Of 29 patients, 24 had completed treatment and been followed for a median of 8.3 months. All 24 had an overall response rate (42% complete response/complete remission with incomplete blood count recovery and 58% partial response), and 83% of patients achieved MRD negativity (100% with complete response and 71% with partial response), Nitin Jain, MD, reported at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

“It appears that the MRD-negativity rate continues to improve over time,” Dr. Jain of MD Anderson Cancer Center, Houston, reported. The MRD-negativity rate increased to 89% at 6 months, and 100% at 9 and 12 months.

All nine patients who reached the 12-month time point are off therapy and are being monitored, he said.

Patients with IGHV mutations generally have favorable long-term outcomes with 10-year progression-free survival rates greater than 60% after receiving standard first-line therapy with fludarabine, cyclophosphamide, and rituximab (FCR). However, ibrutinib is approved for patients with CLL, and obinutuzumab, a glycoengineered type II CD20 monoclonal antibody, was superior to rituximab in the CLL11 trial, Dr. Jain said.

Further, data from the HELIOS trial indicated that combining targeted therapies with chemoimmunotherapy is safe and effective.

iFCG was developed with the intent to limit fludarabine and cyclophosphamide to three courses, potentially reducing short- and long-term toxicity, while maintaining efficacy through the addition of ibrutinib and obinutuzumab, he explained.

Of note, higher pretreatment levels of beta-2 microglobulin were associated with a lower MRD-negativity rate after 3 cycles of iFCG, he said.

In six patients with beta-2 microglobulin of 4 mg/dL or greater, the rate was 50%, compared with 94% in 18 patients with beta-2 microglobulin less than 4 mg/dL.

The patients in the current analysis had a median age of 60 years and adequate organ function. All had IGHV mutation and did not have del(17p) or TP53 mutation. They received three courses of iFCG, including ibrutinib at 420 mg once daily continuously starting at day 1 of course 1 (C1D1); obinutuzumab at 100 mg C1D1, 900 mg C1D2, 1000 mg C1D8, 1000 mg C1D15, 1000 mg C2D1, and 1000 mg C3D1; fludarabine at 25 mg/m² daily for 3 days each course; and cyclophosphamide at 250mg/m² daily for 3 days each course.

Per study protocol, all patients receive ibrutinib with obinutuzumab for courses 4-6. Patients meeting the primary endpoint of complete response/complete remission with incomplete blood count recovery and bone marrow MRD negativity received ibrutinib monotherapy for courses 7-12. Those who did not achieve the primary endpoint received six more courses of ibrutinib and obinutuzumab. All patients who are MRD negative at 1 year stop all therapy, including ibrutinib, while those who are MRD positive at 1 year may continue ibrutinib monotherapy until disease progression.

The target bone marrow MRD-negative rate after 3 cycles of iFCG is 45%. The historic C3 bone marrow MRD-negative rate with standard FCR therapy in patients with IGHV mutation is 26%, Dr. Jain said, noting that the rate in the current analysis compared favorably with both.

The treatment thus far has been generally well tolerated. Toxicities included neutropenia (grade 3 and 4 occurring in 9 and 12 patients, respectively), thrombocytopenia (grade 3 and 4 occurring in 12 and 1 patients, respectively), ALT/AST (grade 3 and 4 occurring in 3 and 1 patients respectively), atrial fibrillation (grade 3 occurring in 1 patient), arthralgia (grade 3 occurring in 1 patient), and infusion-related reaction (grade 2 and 3 occurring in 9 patients and 1 patient, respectively).

Infections included herpes zoster, acute cholecystitis, pulmonary mycobacterium avium complex infection, and pneumocystis pneumonia, which occurred in 1 patient each, and neutropenic fever, which occurred in 4 patients.

“Notably, no patient has progressed or died in the study so far,” Dr. Jain said.

The trial continues to enroll patients, with plans for enrolling a total of 45.

Dr. Jain has received research support from and/or served on an advisory board for Pharmacyclics, Genentech, Abbvie, Prizer, Incyte, BMS, Infinity, ADC Therapeutics, Seattle Genetics, Celgene, Servier, Novartis Novimmune, and Adaptive Biotechnologies.

[email protected]

Image by Lance Liotta

The European Commission (EC) has granted orphan designation to GMI-1271 for the treatment of acute myeloid leukemia (AML).

GMI-1271 is an E-selectin antagonist being developed by GlycoMimetics, Inc.

The product also has orphan designation, fast track designation, and breakthrough therapy designation in the US.

GMI-1271 is currently being evaluated in a phase 1/2 trial of patients with relapsed or refractory AML and patients age 60 and older with newly diagnosed AML.

The patients are receiving GM-1271 in combination with chemotherapy. The relapsed/refractory group is receiving mitoxantrone, etoposide, and cytarabine. The newly diagnosed patients are receiving cytarabine and idarubicin (7+3).

GlycoMimetics plans to present data from this trial at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting as abstracts 2520 and 2560.

The company also plans to present the research at the 22nd Congress of the European Hematology Association (EHA) as abstracts P547 and P203.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

Image by Lance Liotta

The European Commission (EC) has granted orphan designation to GMI-1271 for the treatment of acute myeloid leukemia (AML).

GMI-1271 is an E-selectin antagonist being developed by GlycoMimetics, Inc.

The product also has orphan designation, fast track designation, and breakthrough therapy designation in the US.

GMI-1271 is currently being evaluated in a phase 1/2 trial of patients with relapsed or refractory AML and patients age 60 and older with newly diagnosed AML.

The patients are receiving GM-1271 in combination with chemotherapy. The relapsed/refractory group is receiving mitoxantrone, etoposide, and cytarabine. The newly diagnosed patients are receiving cytarabine and idarubicin (7+3).

GlycoMimetics plans to present data from this trial at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting as abstracts 2520 and 2560.

The company also plans to present the research at the 22nd Congress of the European Hematology Association (EHA) as abstracts P547 and P203.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

Image by Lance Liotta

The European Commission (EC) has granted orphan designation to GMI-1271 for the treatment of acute myeloid leukemia (AML).

GMI-1271 is an E-selectin antagonist being developed by GlycoMimetics, Inc.

The product also has orphan designation, fast track designation, and breakthrough therapy designation in the US.

GMI-1271 is currently being evaluated in a phase 1/2 trial of patients with relapsed or refractory AML and patients age 60 and older with newly diagnosed AML.

The patients are receiving GM-1271 in combination with chemotherapy. The relapsed/refractory group is receiving mitoxantrone, etoposide, and cytarabine. The newly diagnosed patients are receiving cytarabine and idarubicin (7+3).

GlycoMimetics plans to present data from this trial at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting as abstracts 2520 and 2560.

The company also plans to present the research at the 22nd Congress of the European Hematology Association (EHA) as abstracts P547 and P203.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

AML cells

The European Medicines Agency (EMA) has recommended orphan designation for Actimab-A, a product intended to treat patients with newly diagnosed acute myeloid leukemia (AML) who are over the age of 60 and are ineligible for standard induction therapy.

Actimab-A targets CD33, a protein expressed on the surface of AML cells, via the monoclonal antibody, HuM195, which carries the cytotoxic radioisotope actinium-225 to the AML cells.

Actinium Pharmaceuticals, Inc., the company developing Actimab-A, is testing the drug in a phase 2 trial.

Results from a phase 1 trial of the drug were presented at the 2016 ASH Annual Meeting.

At that time, researchers reported results in 18 patients who had been newly diagnosed with AML and were age 60 and older. Their median age was 77 (range, 68-87).

The patients received Actimab-A in combination with low-dose cytarabine. Actimab-A was given at 0.5 μCi/kg/fraction (n=3), 1 μCi/kg/fraction (n=6), 1.5 μCi/kg/fraction (n=3), or 2 μCi/kg/fraction (n=6).

Two patients experienced dose-limiting toxicities. Both had grade 4 thrombocytopenia with marrow aplasia for more than 6 weeks after therapy. One patient was in the 1 µCi/kg/fraction cohort, and the other was in the 2 µCi/kg/fraction cohort.

The maximum-tolerated dose was not reached, but 2 µCi/kg/fraction was chosen as the phase 2 dose.

Grade 3/4 toxicities included neutropenia (n=5), thrombocytopenia (n=9), febrile neutropenia (n=6), pneumonia (n=5), other infections (n=3), atrial fibrillation/syncope (n=1), transient creatinine increase (n=1), generalized fatigue (n=1), hypokalemia (n=1), mucositis (n=1), and rectal hemorrhage (n=1).

Twenty-eight percent of patients (5/18) had objective responses to treatment. Two patients achieved a complete response (CR), 1 had a CR with incomplete platelet recovery, and 2 had a CR with incomplete marrow recovery.

The median duration of response was 9.1 months (range, 4.1-16.9).

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days. 

AML cells

The European Medicines Agency (EMA) has recommended orphan designation for Actimab-A, a product intended to treat patients with newly diagnosed acute myeloid leukemia (AML) who are over the age of 60 and are ineligible for standard induction therapy.

Actimab-A targets CD33, a protein expressed on the surface of AML cells, via the monoclonal antibody, HuM195, which carries the cytotoxic radioisotope actinium-225 to the AML cells.

Actinium Pharmaceuticals, Inc., the company developing Actimab-A, is testing the drug in a phase 2 trial.

Results from a phase 1 trial of the drug were presented at the 2016 ASH Annual Meeting.

At that time, researchers reported results in 18 patients who had been newly diagnosed with AML and were age 60 and older. Their median age was 77 (range, 68-87).

The patients received Actimab-A in combination with low-dose cytarabine. Actimab-A was given at 0.5 μCi/kg/fraction (n=3), 1 μCi/kg/fraction (n=6), 1.5 μCi/kg/fraction (n=3), or 2 μCi/kg/fraction (n=6).

Two patients experienced dose-limiting toxicities. Both had grade 4 thrombocytopenia with marrow aplasia for more than 6 weeks after therapy. One patient was in the 1 µCi/kg/fraction cohort, and the other was in the 2 µCi/kg/fraction cohort.

The maximum-tolerated dose was not reached, but 2 µCi/kg/fraction was chosen as the phase 2 dose.

Grade 3/4 toxicities included neutropenia (n=5), thrombocytopenia (n=9), febrile neutropenia (n=6), pneumonia (n=5), other infections (n=3), atrial fibrillation/syncope (n=1), transient creatinine increase (n=1), generalized fatigue (n=1), hypokalemia (n=1), mucositis (n=1), and rectal hemorrhage (n=1).

Twenty-eight percent of patients (5/18) had objective responses to treatment. Two patients achieved a complete response (CR), 1 had a CR with incomplete platelet recovery, and 2 had a CR with incomplete marrow recovery.

The median duration of response was 9.1 months (range, 4.1-16.9).

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days. 

AML cells

The European Medicines Agency (EMA) has recommended orphan designation for Actimab-A, a product intended to treat patients with newly diagnosed acute myeloid leukemia (AML) who are over the age of 60 and are ineligible for standard induction therapy.

Actimab-A targets CD33, a protein expressed on the surface of AML cells, via the monoclonal antibody, HuM195, which carries the cytotoxic radioisotope actinium-225 to the AML cells.

Actinium Pharmaceuticals, Inc., the company developing Actimab-A, is testing the drug in a phase 2 trial.

Results from a phase 1 trial of the drug were presented at the 2016 ASH Annual Meeting.

At that time, researchers reported results in 18 patients who had been newly diagnosed with AML and were age 60 and older. Their median age was 77 (range, 68-87).

The patients received Actimab-A in combination with low-dose cytarabine. Actimab-A was given at 0.5 μCi/kg/fraction (n=3), 1 μCi/kg/fraction (n=6), 1.5 μCi/kg/fraction (n=3), or 2 μCi/kg/fraction (n=6).

Two patients experienced dose-limiting toxicities. Both had grade 4 thrombocytopenia with marrow aplasia for more than 6 weeks after therapy. One patient was in the 1 µCi/kg/fraction cohort, and the other was in the 2 µCi/kg/fraction cohort.

The maximum-tolerated dose was not reached, but 2 µCi/kg/fraction was chosen as the phase 2 dose.

Grade 3/4 toxicities included neutropenia (n=5), thrombocytopenia (n=9), febrile neutropenia (n=6), pneumonia (n=5), other infections (n=3), atrial fibrillation/syncope (n=1), transient creatinine increase (n=1), generalized fatigue (n=1), hypokalemia (n=1), mucositis (n=1), and rectal hemorrhage (n=1).

Twenty-eight percent of patients (5/18) had objective responses to treatment. Two patients achieved a complete response (CR), 1 had a CR with incomplete platelet recovery, and 2 had a CR with incomplete marrow recovery.

The median duration of response was 9.1 months (range, 4.1-16.9).

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days. 

Photo courtesy of the CDC

New research provides an explanation for the fact that US patients with hematologic malignancies are less likely to enroll in hospice care than patients with solid tumor malignancies.

Results of a national survey suggest that concerns about the adequacy of hospice may prevent hematologic oncologists from referring their patients.

Researchers say this finding, published in Cancer, points to potential means of improving end-of-life care for patients with hematologic malignancies.

Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues carried out this study.

The team conducted a survey of a national sample of hematologic oncologists listed in the publicly available clinical directory of the American Society of Hematology.

More than 57% of physicians who were contacted provided responses, for a total of 349 respondents.

The survey included questions about views regarding the helpfulness and adequacy of home hospice services for patients with hematologic malignancies, as well as factors that would impact oncologists’ likelihood of referring patients to hospice.

More than 68% of hematologic oncologists strongly agreed that hospice care is “helpful” for patients with hematologic malignancies.

However, 46% of the oncologists felt that home hospice is “inadequate” for the needs of patients with hematologic malignancies, when compared to inpatient hospice.

Still, most of the respondents who believed home hospice is inadequate said they would be more likely to refer patients if platelet and red blood cell transfusions were readily available.

“Our findings are important as they shed light on factors that are potential barriers to hospice referrals,” Dr Odejide said. “These findings can be employed to develop targeted interventions to address hospice underuse for patients with blood cancers.” 

Photo courtesy of the CDC

New research provides an explanation for the fact that US patients with hematologic malignancies are less likely to enroll in hospice care than patients with solid tumor malignancies.

Results of a national survey suggest that concerns about the adequacy of hospice may prevent hematologic oncologists from referring their patients.

Researchers say this finding, published in Cancer, points to potential means of improving end-of-life care for patients with hematologic malignancies.

Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues carried out this study.

The team conducted a survey of a national sample of hematologic oncologists listed in the publicly available clinical directory of the American Society of Hematology.

More than 57% of physicians who were contacted provided responses, for a total of 349 respondents.

The survey included questions about views regarding the helpfulness and adequacy of home hospice services for patients with hematologic malignancies, as well as factors that would impact oncologists’ likelihood of referring patients to hospice.

More than 68% of hematologic oncologists strongly agreed that hospice care is “helpful” for patients with hematologic malignancies.

However, 46% of the oncologists felt that home hospice is “inadequate” for the needs of patients with hematologic malignancies, when compared to inpatient hospice.

Still, most of the respondents who believed home hospice is inadequate said they would be more likely to refer patients if platelet and red blood cell transfusions were readily available.

“Our findings are important as they shed light on factors that are potential barriers to hospice referrals,” Dr Odejide said. “These findings can be employed to develop targeted interventions to address hospice underuse for patients with blood cancers.” 

Photo courtesy of the CDC

New research provides an explanation for the fact that US patients with hematologic malignancies are less likely to enroll in hospice care than patients with solid tumor malignancies.

Results of a national survey suggest that concerns about the adequacy of hospice may prevent hematologic oncologists from referring their patients.

Researchers say this finding, published in Cancer, points to potential means of improving end-of-life care for patients with hematologic malignancies.

Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues carried out this study.

The team conducted a survey of a national sample of hematologic oncologists listed in the publicly available clinical directory of the American Society of Hematology.

More than 57% of physicians who were contacted provided responses, for a total of 349 respondents.

The survey included questions about views regarding the helpfulness and adequacy of home hospice services for patients with hematologic malignancies, as well as factors that would impact oncologists’ likelihood of referring patients to hospice.

More than 68% of hematologic oncologists strongly agreed that hospice care is “helpful” for patients with hematologic malignancies.

However, 46% of the oncologists felt that home hospice is “inadequate” for the needs of patients with hematologic malignancies, when compared to inpatient hospice.

Still, most of the respondents who believed home hospice is inadequate said they would be more likely to refer patients if platelet and red blood cell transfusions were readily available.

“Our findings are important as they shed light on factors that are potential barriers to hospice referrals,” Dr Odejide said. “These findings can be employed to develop targeted interventions to address hospice underuse for patients with blood cancers.” 

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

 

NEW YORK – Allogeneic hematopoietic stem cell transplantation (alloHCT) using HLA-compatible donors results in excellent long-term progression-free survival in younger high-risk chronic lymphocytic leukemia (CLL) patients, an analysis of data from a European Society for Blood and Marrow Transplantation registry cohort suggests.

AlloHCT may, in some patients, be preferable to sequential targeted therapy, according to Michel van Gelder, MD.

Sharon Worcester/Frontline Medical News

Patients with relapsed/refractory CLL have very high responses with the kinase inhibitors ibrutinib and idelalisib or the BCL2 inhibitor venetoclax, but the risk of becoming treatment refractory remains a concern when these drugs are used sequentially, particularly in those with high cytogenetic risk resulting from del(17p), TP53 mutation, or del(11q), Dr. van Gelder said at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

This is especially true for those progressing with Richter’s syndrome, who comprise about one-third of patients, he noted.

“On the other hand, allogeneic stem cell transplantation can induce prolonged progression-free survival,” said Dr. van Gelder of Maastricht (the Netherlands) University Medical Center.

Further, most alloHCT patients become minimal residual disease negative, which predicts prolonged progression-free survival (PFS).

“The down-side, of course, is nonrelapse mortality,” he said, noting that NRM depends on factors such as age, performance status, and HLA match.

In a recent risk factor analysis currently pending publication, he and his colleagues found, in a large group of patients, that age, performance status, remission at time of transplant, donor relationship, HLA and sex match each had an impact on 5-year PFS after alloHCT.

The more risk factors a patient had, the worse the outcome, he said.

Based on current knowledge, the place for alloHCT in CLL treatment is in patients with high-risk cytogenetics. Patients can be treated first with a kinase inhibitor or venetoclax followed by transplant, or they can wait for progression and then do the transplant, he said.

Those without high risk cytogenetics but with short PFS after treatment with a kinase inhibitor or venetoclax may also be candidates for alloHCT, he added.

“Preferably they should be young [and] have a good matched donor and low comorbidity,” he said.

In the current study, the focus was on younger CLL patients. “We tried to identify factors that predict for a low 2-year NRM and a high 8-year PFS. We studied the impact of high risk cytogenetics, and, for this study, we chose del(17p) and del(11q), and we tried to officialize the PFS, the relapse incidence, and the nonrelapse mortality of so-called ‘good transplant risk CLL patients’ with these high cytogenetic risk factors,” he explained.

In 197 patients under age 50 years (median 46 years) with a median follow-up of 90 months in an updated EBMT registry cohort, the most important relevant prognostic factor for 2-year NRM was the donor HLA match (adjusted hazard ratio, 2.5 for a matched unrelated donor, 4.0 for a partially matched unrelated donor, both vs. a matched sibling), and predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio, 1.7), and partially HLA matched unrelated donor (HR, 2.8).

High-risk cytogenetics did not significantly impact 8-year PFS, Dr. van Gelder said, noting that this confirms findings from prior studies.

Most of the patients included in the analysis were fludarabine refractory, 70% had del(17p), 35% had del(11q), and the median number of prior treatments was 3. Additionally, 12% had previous autologous transplant, 62% had remission at time of transplant, and most had good performance status, he said.

Conditioning regimens varied by site, 42% of patients had an HLA-matched sibling donor, and 50% had a matched unrelated donor.

Based on the regression model, a reference patient with high risk cytogenetics (del[17p] and/or del[11q]) and good transplant characteristics (age 46 years, no prior autologous stem cell transplantation, remission at the time of alloHCT and HLA- and sex-matched sibling donor) was created. A reference patient with poor transplant characteristics (not in remission at the time of transplant, with an unrelated, non-sex-matched donor) was also created. The predicted 2-year NRM for the good transplant risk patient was 12.1%, and 8-year PFS was more than 50%, Dr. van Gelder said.

For the poor risk patient, 2-year NRM was 37%, and PFS was below 50%, he said.

“So, in conclusion ... good transplant risk young patients with a low nonrelapse mortality and high 8-year progression-free survival can be identified,” he said.

The problem in clinical practice is determining whether – and when – to do a transplant in a young patient, he continued.

“There are a lot of possibilities. Nobody knows, of course, what is the best regimen, but a problem in these patients is that, if they have progression with Richter’s transformation, then you are lost,” he said. “So, if you would like to prevent this, and you have a patient with a low nonrelapse mortality risk, maybe it is better to do the transplant before.”

As for whether alloHCT can be done after kinase inhibitor therapy, the data are limited, but data presented at EBMT 2017 suggest the approach is feasible and effective. In 43 younger patients who underwent alloHCT after ibrutinib treatment, including 37% with TP53 mutation, the 1-year NRM and PFS rates were 9% and 63%, which is “in the same range as in the era before kinase inhibitors,” Dr. van Gelder said regarding the abstract presented by Peter Dreger, MD.

In 32 patients who underwent alloHCT after idelalisib treatment, including 44% with del(17p)/del(11q) and 85% in remission at the time of alloHCT, early follow-up showed that 6-month NRM and PFS was 7% and 83%, respectively, according to another abstract presented by Johannes Schetelig, MD.

“It’s all about balancing the risks. On the one hand you can use sequential therapies. On the other, if you have patients with high-risk cytogenetics [and] CLL in remission and you have a well-matched donor, maybe you should consider the transplant earlier, Dr. van Gelder said. “If you have a good transplant patient in remission, I would propose [that you] don’t wait too long.”

Dr. van Gelder reported having no relevant disclosures.

 

[email protected]

 

NEW YORK – Allogeneic hematopoietic stem cell transplantation (alloHCT) using HLA-compatible donors results in excellent long-term progression-free survival in younger high-risk chronic lymphocytic leukemia (CLL) patients, an analysis of data from a European Society for Blood and Marrow Transplantation registry cohort suggests.

AlloHCT may, in some patients, be preferable to sequential targeted therapy, according to Michel van Gelder, MD.

Sharon Worcester/Frontline Medical News

Patients with relapsed/refractory CLL have very high responses with the kinase inhibitors ibrutinib and idelalisib or the BCL2 inhibitor venetoclax, but the risk of becoming treatment refractory remains a concern when these drugs are used sequentially, particularly in those with high cytogenetic risk resulting from del(17p), TP53 mutation, or del(11q), Dr. van Gelder said at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

This is especially true for those progressing with Richter’s syndrome, who comprise about one-third of patients, he noted.

“On the other hand, allogeneic stem cell transplantation can induce prolonged progression-free survival,” said Dr. van Gelder of Maastricht (the Netherlands) University Medical Center.

Further, most alloHCT patients become minimal residual disease negative, which predicts prolonged progression-free survival (PFS).

“The down-side, of course, is nonrelapse mortality,” he said, noting that NRM depends on factors such as age, performance status, and HLA match.

In a recent risk factor analysis currently pending publication, he and his colleagues found, in a large group of patients, that age, performance status, remission at time of transplant, donor relationship, HLA and sex match each had an impact on 5-year PFS after alloHCT.

The more risk factors a patient had, the worse the outcome, he said.

Based on current knowledge, the place for alloHCT in CLL treatment is in patients with high-risk cytogenetics. Patients can be treated first with a kinase inhibitor or venetoclax followed by transplant, or they can wait for progression and then do the transplant, he said.

Those without high risk cytogenetics but with short PFS after treatment with a kinase inhibitor or venetoclax may also be candidates for alloHCT, he added.

“Preferably they should be young [and] have a good matched donor and low comorbidity,” he said.

In the current study, the focus was on younger CLL patients. “We tried to identify factors that predict for a low 2-year NRM and a high 8-year PFS. We studied the impact of high risk cytogenetics, and, for this study, we chose del(17p) and del(11q), and we tried to officialize the PFS, the relapse incidence, and the nonrelapse mortality of so-called ‘good transplant risk CLL patients’ with these high cytogenetic risk factors,” he explained.

In 197 patients under age 50 years (median 46 years) with a median follow-up of 90 months in an updated EBMT registry cohort, the most important relevant prognostic factor for 2-year NRM was the donor HLA match (adjusted hazard ratio, 2.5 for a matched unrelated donor, 4.0 for a partially matched unrelated donor, both vs. a matched sibling), and predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio, 1.7), and partially HLA matched unrelated donor (HR, 2.8).

High-risk cytogenetics did not significantly impact 8-year PFS, Dr. van Gelder said, noting that this confirms findings from prior studies.

Most of the patients included in the analysis were fludarabine refractory, 70% had del(17p), 35% had del(11q), and the median number of prior treatments was 3. Additionally, 12% had previous autologous transplant, 62% had remission at time of transplant, and most had good performance status, he said.

Conditioning regimens varied by site, 42% of patients had an HLA-matched sibling donor, and 50% had a matched unrelated donor.

Based on the regression model, a reference patient with high risk cytogenetics (del[17p] and/or del[11q]) and good transplant characteristics (age 46 years, no prior autologous stem cell transplantation, remission at the time of alloHCT and HLA- and sex-matched sibling donor) was created. A reference patient with poor transplant characteristics (not in remission at the time of transplant, with an unrelated, non-sex-matched donor) was also created. The predicted 2-year NRM for the good transplant risk patient was 12.1%, and 8-year PFS was more than 50%, Dr. van Gelder said.

For the poor risk patient, 2-year NRM was 37%, and PFS was below 50%, he said.

“So, in conclusion ... good transplant risk young patients with a low nonrelapse mortality and high 8-year progression-free survival can be identified,” he said.

The problem in clinical practice is determining whether – and when – to do a transplant in a young patient, he continued.

“There are a lot of possibilities. Nobody knows, of course, what is the best regimen, but a problem in these patients is that, if they have progression with Richter’s transformation, then you are lost,” he said. “So, if you would like to prevent this, and you have a patient with a low nonrelapse mortality risk, maybe it is better to do the transplant before.”

As for whether alloHCT can be done after kinase inhibitor therapy, the data are limited, but data presented at EBMT 2017 suggest the approach is feasible and effective. In 43 younger patients who underwent alloHCT after ibrutinib treatment, including 37% with TP53 mutation, the 1-year NRM and PFS rates were 9% and 63%, which is “in the same range as in the era before kinase inhibitors,” Dr. van Gelder said regarding the abstract presented by Peter Dreger, MD.

In 32 patients who underwent alloHCT after idelalisib treatment, including 44% with del(17p)/del(11q) and 85% in remission at the time of alloHCT, early follow-up showed that 6-month NRM and PFS was 7% and 83%, respectively, according to another abstract presented by Johannes Schetelig, MD.

“It’s all about balancing the risks. On the one hand you can use sequential therapies. On the other, if you have patients with high-risk cytogenetics [and] CLL in remission and you have a well-matched donor, maybe you should consider the transplant earlier, Dr. van Gelder said. “If you have a good transplant patient in remission, I would propose [that you] don’t wait too long.”

Dr. van Gelder reported having no relevant disclosures.

 

[email protected]

 

NEW YORK – Allogeneic hematopoietic stem cell transplantation (alloHCT) using HLA-compatible donors results in excellent long-term progression-free survival in younger high-risk chronic lymphocytic leukemia (CLL) patients, an analysis of data from a European Society for Blood and Marrow Transplantation registry cohort suggests.

AlloHCT may, in some patients, be preferable to sequential targeted therapy, according to Michel van Gelder, MD.

Sharon Worcester/Frontline Medical News

Patients with relapsed/refractory CLL have very high responses with the kinase inhibitors ibrutinib and idelalisib or the BCL2 inhibitor venetoclax, but the risk of becoming treatment refractory remains a concern when these drugs are used sequentially, particularly in those with high cytogenetic risk resulting from del(17p), TP53 mutation, or del(11q), Dr. van Gelder said at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.

This is especially true for those progressing with Richter’s syndrome, who comprise about one-third of patients, he noted.

“On the other hand, allogeneic stem cell transplantation can induce prolonged progression-free survival,” said Dr. van Gelder of Maastricht (the Netherlands) University Medical Center.

Further, most alloHCT patients become minimal residual disease negative, which predicts prolonged progression-free survival (PFS).

“The down-side, of course, is nonrelapse mortality,” he said, noting that NRM depends on factors such as age, performance status, and HLA match.

In a recent risk factor analysis currently pending publication, he and his colleagues found, in a large group of patients, that age, performance status, remission at time of transplant, donor relationship, HLA and sex match each had an impact on 5-year PFS after alloHCT.

The more risk factors a patient had, the worse the outcome, he said.

Based on current knowledge, the place for alloHCT in CLL treatment is in patients with high-risk cytogenetics. Patients can be treated first with a kinase inhibitor or venetoclax followed by transplant, or they can wait for progression and then do the transplant, he said.

Those without high risk cytogenetics but with short PFS after treatment with a kinase inhibitor or venetoclax may also be candidates for alloHCT, he added.

“Preferably they should be young [and] have a good matched donor and low comorbidity,” he said.

In the current study, the focus was on younger CLL patients. “We tried to identify factors that predict for a low 2-year NRM and a high 8-year PFS. We studied the impact of high risk cytogenetics, and, for this study, we chose del(17p) and del(11q), and we tried to officialize the PFS, the relapse incidence, and the nonrelapse mortality of so-called ‘good transplant risk CLL patients’ with these high cytogenetic risk factors,” he explained.

In 197 patients under age 50 years (median 46 years) with a median follow-up of 90 months in an updated EBMT registry cohort, the most important relevant prognostic factor for 2-year NRM was the donor HLA match (adjusted hazard ratio, 2.5 for a matched unrelated donor, 4.0 for a partially matched unrelated donor, both vs. a matched sibling), and predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio, 1.7), and partially HLA matched unrelated donor (HR, 2.8).

High-risk cytogenetics did not significantly impact 8-year PFS, Dr. van Gelder said, noting that this confirms findings from prior studies.

Most of the patients included in the analysis were fludarabine refractory, 70% had del(17p), 35% had del(11q), and the median number of prior treatments was 3. Additionally, 12% had previous autologous transplant, 62% had remission at time of transplant, and most had good performance status, he said.

Conditioning regimens varied by site, 42% of patients had an HLA-matched sibling donor, and 50% had a matched unrelated donor.

Based on the regression model, a reference patient with high risk cytogenetics (del[17p] and/or del[11q]) and good transplant characteristics (age 46 years, no prior autologous stem cell transplantation, remission at the time of alloHCT and HLA- and sex-matched sibling donor) was created. A reference patient with poor transplant characteristics (not in remission at the time of transplant, with an unrelated, non-sex-matched donor) was also created. The predicted 2-year NRM for the good transplant risk patient was 12.1%, and 8-year PFS was more than 50%, Dr. van Gelder said.

For the poor risk patient, 2-year NRM was 37%, and PFS was below 50%, he said.

“So, in conclusion ... good transplant risk young patients with a low nonrelapse mortality and high 8-year progression-free survival can be identified,” he said.

The problem in clinical practice is determining whether – and when – to do a transplant in a young patient, he continued.

“There are a lot of possibilities. Nobody knows, of course, what is the best regimen, but a problem in these patients is that, if they have progression with Richter’s transformation, then you are lost,” he said. “So, if you would like to prevent this, and you have a patient with a low nonrelapse mortality risk, maybe it is better to do the transplant before.”

As for whether alloHCT can be done after kinase inhibitor therapy, the data are limited, but data presented at EBMT 2017 suggest the approach is feasible and effective. In 43 younger patients who underwent alloHCT after ibrutinib treatment, including 37% with TP53 mutation, the 1-year NRM and PFS rates were 9% and 63%, which is “in the same range as in the era before kinase inhibitors,” Dr. van Gelder said regarding the abstract presented by Peter Dreger, MD.

In 32 patients who underwent alloHCT after idelalisib treatment, including 44% with del(17p)/del(11q) and 85% in remission at the time of alloHCT, early follow-up showed that 6-month NRM and PFS was 7% and 83%, respectively, according to another abstract presented by Johannes Schetelig, MD.

“It’s all about balancing the risks. On the one hand you can use sequential therapies. On the other, if you have patients with high-risk cytogenetics [and] CLL in remission and you have a well-matched donor, maybe you should consider the transplant earlier, Dr. van Gelder said. “If you have a good transplant patient in remission, I would propose [that you] don’t wait too long.”

Dr. van Gelder reported having no relevant disclosures.

 

[email protected]