Leukemia, Myelodysplasia, Transplantation

For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC), based on a retrospective study involving more than 1,700 patients.

OlegMalyshev/Getty Images

Within 100 days of treatment, patients who underwent MAC were significantly more likely to develop a bacterial infection, and develop it at an earlier date, than patients who had undergone RIC/NMA, reported lead author Celalettin Ustun, MD, of Rush University in Chicago, and colleagues.

“The incidence of infections, a common and often severe complication of alloHCT, is expected to be lower after RIC/NMA compared with MAC and thus contribute to the decreased [nonrelapse mortality],” the investigators wrote in Blood Advances, noting that this hypothesis has previously lacked supporting data, prompting the present study.

The retrospective analysis involved 1,755 patients with AML who were in first complete remission. Data were drawn from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary end point was incidence of infection within 100 days after T-cell replete alloHCT in patients receiving MAC (n = 978) versus those who underwent RIC/NMA (n = 777). Secondary end points included comparisons of infection types and infection density.

Patients who received RIC/NMA were generally older and more likely to have myelodysplastic syndrome than patients in the MAC group; the groups were otherwise similar, based on comorbidities, cytogenetic risks, and Karnofsky performance scores.

The proportion of patients who developed at least one infection was comparable between groups: 61% of MAC patients versus 58% of RIC/NMA patients (P = .21), but further analysis showed that MAC was in fact associated with some relatively increased risks. For instance, patients in the MAC group tended to develop infections sooner than patients treated with RIC/NMA (21 vs. 15 days), and more patients treated with MAC had at least one bacterial infection by day 100 (46% vs. 37%).

Although the proportion of patients developing at least one viral infection was slightly lower in the MAC group than the RIC/NMA group (34% vs. 39%), overall infection density was higher, which takes into account multiple infections.

The increased bacterial infections after MAC were caused by gram-positive bacteria, while the increased viral infections with RIC/NMA were caused by cytomegalovirus, the investigators reported.

“RIC/NMA alloHCT is associated with a decreased risk of any infection and particularly early bacterial infections,” the investigators wrote. “The risk of viral and fungal infections per days at risk is similar.”

The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.

SOURCE: Ustun C et al. Blood Adv. 2019 Sep 10;3(17):2525-36.

For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC), based on a retrospective study involving more than 1,700 patients.

OlegMalyshev/Getty Images

Within 100 days of treatment, patients who underwent MAC were significantly more likely to develop a bacterial infection, and develop it at an earlier date, than patients who had undergone RIC/NMA, reported lead author Celalettin Ustun, MD, of Rush University in Chicago, and colleagues.

“The incidence of infections, a common and often severe complication of alloHCT, is expected to be lower after RIC/NMA compared with MAC and thus contribute to the decreased [nonrelapse mortality],” the investigators wrote in Blood Advances, noting that this hypothesis has previously lacked supporting data, prompting the present study.

The retrospective analysis involved 1,755 patients with AML who were in first complete remission. Data were drawn from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary end point was incidence of infection within 100 days after T-cell replete alloHCT in patients receiving MAC (n = 978) versus those who underwent RIC/NMA (n = 777). Secondary end points included comparisons of infection types and infection density.

Patients who received RIC/NMA were generally older and more likely to have myelodysplastic syndrome than patients in the MAC group; the groups were otherwise similar, based on comorbidities, cytogenetic risks, and Karnofsky performance scores.

The proportion of patients who developed at least one infection was comparable between groups: 61% of MAC patients versus 58% of RIC/NMA patients (P = .21), but further analysis showed that MAC was in fact associated with some relatively increased risks. For instance, patients in the MAC group tended to develop infections sooner than patients treated with RIC/NMA (21 vs. 15 days), and more patients treated with MAC had at least one bacterial infection by day 100 (46% vs. 37%).

Although the proportion of patients developing at least one viral infection was slightly lower in the MAC group than the RIC/NMA group (34% vs. 39%), overall infection density was higher, which takes into account multiple infections.

The increased bacterial infections after MAC were caused by gram-positive bacteria, while the increased viral infections with RIC/NMA were caused by cytomegalovirus, the investigators reported.

“RIC/NMA alloHCT is associated with a decreased risk of any infection and particularly early bacterial infections,” the investigators wrote. “The risk of viral and fungal infections per days at risk is similar.”

The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.

SOURCE: Ustun C et al. Blood Adv. 2019 Sep 10;3(17):2525-36.

For patients with acute myeloid leukemia (AML) in need of allogeneic hematopoietic cell transplantation (alloHCT), reduced-intensity/nonmyeloablative conditioning (RIC/NMA) offers a lower risk of infection than myeloablative conditioning (MAC), based on a retrospective study involving more than 1,700 patients.

OlegMalyshev/Getty Images

Within 100 days of treatment, patients who underwent MAC were significantly more likely to develop a bacterial infection, and develop it at an earlier date, than patients who had undergone RIC/NMA, reported lead author Celalettin Ustun, MD, of Rush University in Chicago, and colleagues.

“The incidence of infections, a common and often severe complication of alloHCT, is expected to be lower after RIC/NMA compared with MAC and thus contribute to the decreased [nonrelapse mortality],” the investigators wrote in Blood Advances, noting that this hypothesis has previously lacked supporting data, prompting the present study.

The retrospective analysis involved 1,755 patients with AML who were in first complete remission. Data were drawn from the Center for International Blood and Marrow Transplant Research (CIBMTR). The primary end point was incidence of infection within 100 days after T-cell replete alloHCT in patients receiving MAC (n = 978) versus those who underwent RIC/NMA (n = 777). Secondary end points included comparisons of infection types and infection density.

Patients who received RIC/NMA were generally older and more likely to have myelodysplastic syndrome than patients in the MAC group; the groups were otherwise similar, based on comorbidities, cytogenetic risks, and Karnofsky performance scores.

The proportion of patients who developed at least one infection was comparable between groups: 61% of MAC patients versus 58% of RIC/NMA patients (P = .21), but further analysis showed that MAC was in fact associated with some relatively increased risks. For instance, patients in the MAC group tended to develop infections sooner than patients treated with RIC/NMA (21 vs. 15 days), and more patients treated with MAC had at least one bacterial infection by day 100 (46% vs. 37%).

Although the proportion of patients developing at least one viral infection was slightly lower in the MAC group than the RIC/NMA group (34% vs. 39%), overall infection density was higher, which takes into account multiple infections.

The increased bacterial infections after MAC were caused by gram-positive bacteria, while the increased viral infections with RIC/NMA were caused by cytomegalovirus, the investigators reported.

“RIC/NMA alloHCT is associated with a decreased risk of any infection and particularly early bacterial infections,” the investigators wrote. “The risk of viral and fungal infections per days at risk is similar.”

The Center for International Blood and Marrow Transplant Research is supported by grants from the U.S. government and several pharmaceutical companies. The investigators reported having no conflicts of interest.

SOURCE: Ustun C et al. Blood Adv. 2019 Sep 10;3(17):2525-36.

The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.

Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.

Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.

The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.

There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.

The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.

The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).

Results

There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).

The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.

Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).

“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”

The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.

Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.

[email protected]

SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.

The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.

Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.

Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.

The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.

There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.

The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.

The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).

Results

There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).

The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.

Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).

“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”

The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.

Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.

[email protected]

SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.

The presence of complex karyotype (CK) does not affect survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who are treated with idelalisib, according to a new analysis.

Researchers analyzed data from two clinical trials of idelalisib, given alone or in combination with rituximab, and found no significant difference in overall survival (OS) between patients with and without CK.

Karl-Anton Kreuzer, MD, of the University of Cologne (Germany), and colleagues described these findings in a letter to Leukemia.

The researchers evaluated patients with previously treated CLL who were enrolled in a phase 3 trial and received either idelalisib plus rituximab or rituximab plus placebo. Patients from either treatment arm could enroll in an extension study of idelalisib monotherapy.

There were 220 patients randomized to idelalisib plus rituximab (n = 110) or placebo plus rituximab (n = 110) in the primary study, and 161 of these patients were enrolled in the extension study.

The final analysis included 120 patients who were successfully karyotyped – 63 from the idelalisib-rituximab arm and 57 from the placebo-rituximab arm. Less than half of patients in each arm were CK-positive – 41% (26/63) of the idelalisib arm and 42% (24/57) of the placebo arm.

The researchers wrote that baseline characteristics were “mostly balanced” between the CK-positive and CK-negative groups in each treatment arm. The only significant difference was that fewer CK-positive patients in the placebo arm had a creatinine clearance of 30-59 mL/min (P = .0324).

Results

There were no significant differences in outcomes between CK-positive and CK-negative patients who received idelalisib and rituximab. The overall response rate was 81% in CK-positive patients and 89% in CK-negative patients (P = .3509). The median progression-free survival was 20.9 months and 19.4 months, respectively (P = .5848).

The median OS was 28.3 months in the CK-positive group and 49.7 months in the CK-negative group (P = .2099). The copresence of CK and del(17p), TP53 mutation, or del(11q) didn’t significantly affect OS, the researchers noted.

Among all CK-positive patients, the median OS was 28.3 months in the idelalisib-rituximab arm and 9.2 months in the placebo-rituximab arm (P = .0412).

“Our analysis suggests that CK-positive patients treated with idelalisib/rituximab did not exhibit a significantly shortened survival compared with those who were CK negative,” the researchers wrote. “In addition, the primary beneficial effect of adding idelalisib to rituximab treatment in [relapsed/refractory] CLL patients with CK was reflected in OS prolongation compared to those who received only rituximab.”

The researchers noted that this study has limitations, so prospective clinical trials are needed to guide treatment of patients with relapsed/refractory CLL and CK.

Both trials of idelalisib were sponsored by Gilead. The researchers reported relationships, including employment, with Gilead and other companies. They also disclosed funding from the German government and from nonprofit organizations in Germany.

[email protected]

SOURCE: Kreuzer K-A et al. Leukemia. 2019 Aug 19. doi: 10.1038/s41375-019-0533-6.

The Food and Drug Administration has granted breakthrough therapy designation to acalabrutinib (Calquence) as a monotherapy for adults with chronic lymphocytic leukemia (CLL).

The Bruton tyrosine kinase inhibitor is already approved for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy, and multiple trials are underway to evaluate the drug’s use in a variety of B-cell malignancies, according to the drug’s sponsor, AstraZeneca.

The current designation was based on preliminary results from two phase 3 trials – ELEVATE-TN and ASCEND. In the three-arm ELEVATE-TN trial, researchers evaluated acalabrutinib alone or in combination with obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. In the two-arm ASCEND trial, previously treated patients with CLL were randomized to receive acalabrutinib monotherapy or the physician’s choice of either rituximab plus idelalisib or rituximab plus bendamustine.

Interim analyses of the two trials showed that acalabrutinib alone, or in combination, significantly improved progression-free survival without raising safety concerns.

Breakthrough therapy designation allows for an expedited review by the FDA for treatments aimed at treating serious conditions where there is preliminary clinical evidence showing a substantial improvement over an available therapy or a clinically significant endpoint.

[email protected]

The Food and Drug Administration has granted breakthrough therapy designation to acalabrutinib (Calquence) as a monotherapy for adults with chronic lymphocytic leukemia (CLL).

The Bruton tyrosine kinase inhibitor is already approved for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy, and multiple trials are underway to evaluate the drug’s use in a variety of B-cell malignancies, according to the drug’s sponsor, AstraZeneca.

The current designation was based on preliminary results from two phase 3 trials – ELEVATE-TN and ASCEND. In the three-arm ELEVATE-TN trial, researchers evaluated acalabrutinib alone or in combination with obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. In the two-arm ASCEND trial, previously treated patients with CLL were randomized to receive acalabrutinib monotherapy or the physician’s choice of either rituximab plus idelalisib or rituximab plus bendamustine.

Interim analyses of the two trials showed that acalabrutinib alone, or in combination, significantly improved progression-free survival without raising safety concerns.

Breakthrough therapy designation allows for an expedited review by the FDA for treatments aimed at treating serious conditions where there is preliminary clinical evidence showing a substantial improvement over an available therapy or a clinically significant endpoint.

[email protected]

The Food and Drug Administration has granted breakthrough therapy designation to acalabrutinib (Calquence) as a monotherapy for adults with chronic lymphocytic leukemia (CLL).

The Bruton tyrosine kinase inhibitor is already approved for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy, and multiple trials are underway to evaluate the drug’s use in a variety of B-cell malignancies, according to the drug’s sponsor, AstraZeneca.

The current designation was based on preliminary results from two phase 3 trials – ELEVATE-TN and ASCEND. In the three-arm ELEVATE-TN trial, researchers evaluated acalabrutinib alone or in combination with obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. In the two-arm ASCEND trial, previously treated patients with CLL were randomized to receive acalabrutinib monotherapy or the physician’s choice of either rituximab plus idelalisib or rituximab plus bendamustine.

Interim analyses of the two trials showed that acalabrutinib alone, or in combination, significantly improved progression-free survival without raising safety concerns.

Breakthrough therapy designation allows for an expedited review by the FDA for treatments aimed at treating serious conditions where there is preliminary clinical evidence showing a substantial improvement over an available therapy or a clinically significant endpoint.

[email protected]

The Bruton tyrosine kinase (BTK) inhibitor zanubrutinib appears safe and effective for patients with B-cell malignancies, according to results from a phase 1 trial.

©Ed Uthman/Flickr

Among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the overall response rate was 96.2%, reported Constantine Si Lun Tam, MD, of Peter MacCallum Cancer Centre in Melbourne and colleagues.

“Zanubrutinib (BGB-3111) is a highly specific next-generation BTK inhibitor with favorable oral bioavailability, as shown in preclinical studies,” the investigators wrote in Blood. “Compared with ibrutinib, zanubrutinib has shown greater selectivity for BTK and fewer off-target effects in multiple in vitro enzymatic and cell-based assays.”

The current, open-label trial involved 144 patients with B-cell malignancies. To determine optimal dosing, the investigators recruited 17 patients with relapsed/refractory B-cell malignancies who had received at least one prior therapy. The dose expansion part of the study assessed responses in multiple cohorts, including patients with CLL/SLL, mantle cell lymphoma, and Waldenström macroglobulinemia. The primary endpoints were safety and tolerability, including maximum tolerated dose. Efficacy findings were also reported.

During dose escalation, no dose-limiting toxicities were observed, so the highest dose – 320 mg once daily or 160 mg twice daily – was selected for further testing.

The investigators highlighted efficacy and safety findings from 94 patients with CLL/SLL who were involved in dose expansion. Although nearly one-quarter (23.4%) were treatment-naive, the median number of prior therapies was two, and some patients had high-risk features, such as adverse cytogenetics, including 19.1% with a TP53 mutation and 23.3% with a 17p deletion. After a median follow-up of 13.7 months, 94.7% of these patients were still undergoing treatment.

Out of the initial 94 patients with CLL/SLL, 78 were evaluable for efficacy. The overall response rate was 96.2%, including two (2.6%) complete responses, 63 (80.8%) partial responses, and 10 (12.8%) partial responses with lymphocytosis. The median progression-free survival had not been reached, and the 12-month estimated progression-free survival was 100%.

In regard to safety, the most common adverse events were contusion (35.1%), upper respiratory tract infection (33.0%), cough (25.5%), diarrhea (21.3%), fatigue (19.1%), back pain (14.9%), hematuria (14.9%), headache (13.8%), nausea (13.8%), rash (12.8%), arthralgia (11.7%), muscle spasms (11.7%), and urinary tract infection (10.6%).

A number of other adverse events were reported, although these occurred in less than 10% of patients.

More than one-third of patients (36.2%) experienced grade 3 or higher adverse events, with neutropenia being most common (6.4%), followed by pneumonia , hypertension, and anemia, which each occurred in 2.1% of patients, and less commonly, back pain, nausea, urinary tract infection, purpura, cellulitis, and squamous cell carcinoma of the skin, which each occurred in 1.1% of patients.

“In this first-in-human study, zanubrutinib demonstrated encouraging activity in patients with relapsed/refractory and treatment-naive CLL/SLL, with good tolerability,” the investigators concluded. “Two ongoing randomized studies of zanubrutinib versus ibrutinib (NCT03053440 and NCT03734016) aim to determine whether consistent, continuous BTK blockade with a selective inhibitor results in fewer off-target effects and translates into improvements in disease control.”

The study was funded by BeiGene USA, which is developing the drug. The investigators reported relationships with the study sponsor, as well as Janssen, Pharmacyclics, AbbVie, and others.

SOURCE: Tam CSL et al. Blood. 2019 Jul 24. doi: 10.1182/blood.2019001160.

The Bruton tyrosine kinase (BTK) inhibitor zanubrutinib appears safe and effective for patients with B-cell malignancies, according to results from a phase 1 trial.

©Ed Uthman/Flickr

Among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the overall response rate was 96.2%, reported Constantine Si Lun Tam, MD, of Peter MacCallum Cancer Centre in Melbourne and colleagues.

“Zanubrutinib (BGB-3111) is a highly specific next-generation BTK inhibitor with favorable oral bioavailability, as shown in preclinical studies,” the investigators wrote in Blood. “Compared with ibrutinib, zanubrutinib has shown greater selectivity for BTK and fewer off-target effects in multiple in vitro enzymatic and cell-based assays.”

The current, open-label trial involved 144 patients with B-cell malignancies. To determine optimal dosing, the investigators recruited 17 patients with relapsed/refractory B-cell malignancies who had received at least one prior therapy. The dose expansion part of the study assessed responses in multiple cohorts, including patients with CLL/SLL, mantle cell lymphoma, and Waldenström macroglobulinemia. The primary endpoints were safety and tolerability, including maximum tolerated dose. Efficacy findings were also reported.

During dose escalation, no dose-limiting toxicities were observed, so the highest dose – 320 mg once daily or 160 mg twice daily – was selected for further testing.

The investigators highlighted efficacy and safety findings from 94 patients with CLL/SLL who were involved in dose expansion. Although nearly one-quarter (23.4%) were treatment-naive, the median number of prior therapies was two, and some patients had high-risk features, such as adverse cytogenetics, including 19.1% with a TP53 mutation and 23.3% with a 17p deletion. After a median follow-up of 13.7 months, 94.7% of these patients were still undergoing treatment.

Out of the initial 94 patients with CLL/SLL, 78 were evaluable for efficacy. The overall response rate was 96.2%, including two (2.6%) complete responses, 63 (80.8%) partial responses, and 10 (12.8%) partial responses with lymphocytosis. The median progression-free survival had not been reached, and the 12-month estimated progression-free survival was 100%.

In regard to safety, the most common adverse events were contusion (35.1%), upper respiratory tract infection (33.0%), cough (25.5%), diarrhea (21.3%), fatigue (19.1%), back pain (14.9%), hematuria (14.9%), headache (13.8%), nausea (13.8%), rash (12.8%), arthralgia (11.7%), muscle spasms (11.7%), and urinary tract infection (10.6%).

A number of other adverse events were reported, although these occurred in less than 10% of patients.

More than one-third of patients (36.2%) experienced grade 3 or higher adverse events, with neutropenia being most common (6.4%), followed by pneumonia , hypertension, and anemia, which each occurred in 2.1% of patients, and less commonly, back pain, nausea, urinary tract infection, purpura, cellulitis, and squamous cell carcinoma of the skin, which each occurred in 1.1% of patients.

“In this first-in-human study, zanubrutinib demonstrated encouraging activity in patients with relapsed/refractory and treatment-naive CLL/SLL, with good tolerability,” the investigators concluded. “Two ongoing randomized studies of zanubrutinib versus ibrutinib (NCT03053440 and NCT03734016) aim to determine whether consistent, continuous BTK blockade with a selective inhibitor results in fewer off-target effects and translates into improvements in disease control.”

The study was funded by BeiGene USA, which is developing the drug. The investigators reported relationships with the study sponsor, as well as Janssen, Pharmacyclics, AbbVie, and others.

SOURCE: Tam CSL et al. Blood. 2019 Jul 24. doi: 10.1182/blood.2019001160.

The Bruton tyrosine kinase (BTK) inhibitor zanubrutinib appears safe and effective for patients with B-cell malignancies, according to results from a phase 1 trial.

©Ed Uthman/Flickr

Among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the overall response rate was 96.2%, reported Constantine Si Lun Tam, MD, of Peter MacCallum Cancer Centre in Melbourne and colleagues.

“Zanubrutinib (BGB-3111) is a highly specific next-generation BTK inhibitor with favorable oral bioavailability, as shown in preclinical studies,” the investigators wrote in Blood. “Compared with ibrutinib, zanubrutinib has shown greater selectivity for BTK and fewer off-target effects in multiple in vitro enzymatic and cell-based assays.”

The current, open-label trial involved 144 patients with B-cell malignancies. To determine optimal dosing, the investigators recruited 17 patients with relapsed/refractory B-cell malignancies who had received at least one prior therapy. The dose expansion part of the study assessed responses in multiple cohorts, including patients with CLL/SLL, mantle cell lymphoma, and Waldenström macroglobulinemia. The primary endpoints were safety and tolerability, including maximum tolerated dose. Efficacy findings were also reported.

During dose escalation, no dose-limiting toxicities were observed, so the highest dose – 320 mg once daily or 160 mg twice daily – was selected for further testing.

The investigators highlighted efficacy and safety findings from 94 patients with CLL/SLL who were involved in dose expansion. Although nearly one-quarter (23.4%) were treatment-naive, the median number of prior therapies was two, and some patients had high-risk features, such as adverse cytogenetics, including 19.1% with a TP53 mutation and 23.3% with a 17p deletion. After a median follow-up of 13.7 months, 94.7% of these patients were still undergoing treatment.

Out of the initial 94 patients with CLL/SLL, 78 were evaluable for efficacy. The overall response rate was 96.2%, including two (2.6%) complete responses, 63 (80.8%) partial responses, and 10 (12.8%) partial responses with lymphocytosis. The median progression-free survival had not been reached, and the 12-month estimated progression-free survival was 100%.

In regard to safety, the most common adverse events were contusion (35.1%), upper respiratory tract infection (33.0%), cough (25.5%), diarrhea (21.3%), fatigue (19.1%), back pain (14.9%), hematuria (14.9%), headache (13.8%), nausea (13.8%), rash (12.8%), arthralgia (11.7%), muscle spasms (11.7%), and urinary tract infection (10.6%).

A number of other adverse events were reported, although these occurred in less than 10% of patients.

More than one-third of patients (36.2%) experienced grade 3 or higher adverse events, with neutropenia being most common (6.4%), followed by pneumonia , hypertension, and anemia, which each occurred in 2.1% of patients, and less commonly, back pain, nausea, urinary tract infection, purpura, cellulitis, and squamous cell carcinoma of the skin, which each occurred in 1.1% of patients.

“In this first-in-human study, zanubrutinib demonstrated encouraging activity in patients with relapsed/refractory and treatment-naive CLL/SLL, with good tolerability,” the investigators concluded. “Two ongoing randomized studies of zanubrutinib versus ibrutinib (NCT03053440 and NCT03734016) aim to determine whether consistent, continuous BTK blockade with a selective inhibitor results in fewer off-target effects and translates into improvements in disease control.”

The study was funded by BeiGene USA, which is developing the drug. The investigators reported relationships with the study sponsor, as well as Janssen, Pharmacyclics, AbbVie, and others.

SOURCE: Tam CSL et al. Blood. 2019 Jul 24. doi: 10.1182/blood.2019001160.

Patients with previously untreated chronic lymphocytic leukemia (CLL) aged 70 years or younger who received ibrutinib/rituximab therapy experienced significantly greater progression-free survival, compared with those who received standard chemotherapy with fludarabine, cyclophosphamide, and rituximab (89.4% vs. 72.9% at 3 years; hazard ratio, 0.35; 95% confidence interval, 0.22-0.56; P less than .001), according to results from a randomized, phase 3 trial published in the New England Journal of Medicine (2019;381:432-43).

Ed Uthman/Flickr

We first reported on the results of this trial when they were presented at the annual meeting of the American Society of Hematology. Find our coverage at the link below.

[email protected]

Patients with previously untreated chronic lymphocytic leukemia (CLL) aged 70 years or younger who received ibrutinib/rituximab therapy experienced significantly greater progression-free survival, compared with those who received standard chemotherapy with fludarabine, cyclophosphamide, and rituximab (89.4% vs. 72.9% at 3 years; hazard ratio, 0.35; 95% confidence interval, 0.22-0.56; P less than .001), according to results from a randomized, phase 3 trial published in the New England Journal of Medicine (2019;381:432-43).

Ed Uthman/Flickr

We first reported on the results of this trial when they were presented at the annual meeting of the American Society of Hematology. Find our coverage at the link below.

[email protected]

Patients with previously untreated chronic lymphocytic leukemia (CLL) aged 70 years or younger who received ibrutinib/rituximab therapy experienced significantly greater progression-free survival, compared with those who received standard chemotherapy with fludarabine, cyclophosphamide, and rituximab (89.4% vs. 72.9% at 3 years; hazard ratio, 0.35; 95% confidence interval, 0.22-0.56; P less than .001), according to results from a randomized, phase 3 trial published in the New England Journal of Medicine (2019;381:432-43).

Ed Uthman/Flickr

We first reported on the results of this trial when they were presented at the annual meeting of the American Society of Hematology. Find our coverage at the link below.

[email protected]

Mutations in Bruton’s tyrosine kinase (BTK) are associated with progression of chronic lymphocytic leukemia (CLL) in patients taking ibrutinib, according to a new study.

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

Researchers analyzed a “real-life” cohort of CLL patients taking ibrutinib for about 3 years and found that patients with BTK mutations were significantly more likely to progress (P = .0005).

“Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment,” wrote Anne Quinquenel, MD, PhD, of Hôpital Robert Debré, Université Reims (France) Champagne-Ardenne, and colleagues. Their report is in Blood.

The researchers studied 57 CLL patients who were still on ibrutinib after at least 3 years and provided fresh blood samples. The median time between the start of ibrutinib and sample collection was 3.5 years.

All 57 patients had minimal residual disease at baseline. Of the 55 patients with response data available, 48 had a partial response, and 7 had a partial response with lymphocytosis.

Mutational profiling was possible in 30 patients who had a CLL clone greater than or equal to 0.5 x 10⁹/L.

BTK mutations were present in 17 of the 30 patients (57%). There were 20 BTK mutations in total, all were at C481, and 14 were at C481S.

The researchers also identified 15 patients with TP53 mutations and 4 patients with phospholipase Cg2 (PLCG2) mutations. All 4 patients with PLCG2 mutations also had a BTK mutation and a TP53 mutation.

However, there were no significant associations between BTK mutations and other mutations. BTK mutations were not associated with the number of previous therapies a patient received or the need for ibrutinib dose interruptions or reductions.

The researchers assessed CLL progression at median of 8.5 months from sample collection and found the presence of a BTK mutation was significantly associated with progression (P = .0005).

Of the 17 patients with a BTK mutation, 14 progressed with one case of Richter’s syndrome. Three patients who progressed were still on ibrutinib, nine patients received venetoclax, and two patients died without further treatment.

Of the 13 patients without BTK mutations, just two patients progressed. One patient died without further treatment, and the other received venetoclax.

The event-free survival was significantly shorter in patients with a BTK mutation than in those without (P = .0380), but there was no significant difference in overall survival.

This research was supported by Sunesis Pharmaceuticals and the Force Hemato (fonds de recherche clinique en hématologie) foundation. The researchers reported relationships with Janssen, Gilead, Roche, and AbbVie.

[email protected]

SOURCE: Quinquenel A et al. Blood. 2019 Jun 26. doi: 10.1182/blood.2019000854.

Mutations in Bruton’s tyrosine kinase (BTK) are associated with progression of chronic lymphocytic leukemia (CLL) in patients taking ibrutinib, according to a new study.

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

Researchers analyzed a “real-life” cohort of CLL patients taking ibrutinib for about 3 years and found that patients with BTK mutations were significantly more likely to progress (P = .0005).

“Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment,” wrote Anne Quinquenel, MD, PhD, of Hôpital Robert Debré, Université Reims (France) Champagne-Ardenne, and colleagues. Their report is in Blood.

The researchers studied 57 CLL patients who were still on ibrutinib after at least 3 years and provided fresh blood samples. The median time between the start of ibrutinib and sample collection was 3.5 years.

All 57 patients had minimal residual disease at baseline. Of the 55 patients with response data available, 48 had a partial response, and 7 had a partial response with lymphocytosis.

Mutational profiling was possible in 30 patients who had a CLL clone greater than or equal to 0.5 x 10⁹/L.

BTK mutations were present in 17 of the 30 patients (57%). There were 20 BTK mutations in total, all were at C481, and 14 were at C481S.

The researchers also identified 15 patients with TP53 mutations and 4 patients with phospholipase Cg2 (PLCG2) mutations. All 4 patients with PLCG2 mutations also had a BTK mutation and a TP53 mutation.

However, there were no significant associations between BTK mutations and other mutations. BTK mutations were not associated with the number of previous therapies a patient received or the need for ibrutinib dose interruptions or reductions.

The researchers assessed CLL progression at median of 8.5 months from sample collection and found the presence of a BTK mutation was significantly associated with progression (P = .0005).

Of the 17 patients with a BTK mutation, 14 progressed with one case of Richter’s syndrome. Three patients who progressed were still on ibrutinib, nine patients received venetoclax, and two patients died without further treatment.

Of the 13 patients without BTK mutations, just two patients progressed. One patient died without further treatment, and the other received venetoclax.

The event-free survival was significantly shorter in patients with a BTK mutation than in those without (P = .0380), but there was no significant difference in overall survival.

This research was supported by Sunesis Pharmaceuticals and the Force Hemato (fonds de recherche clinique en hématologie) foundation. The researchers reported relationships with Janssen, Gilead, Roche, and AbbVie.

[email protected]

SOURCE: Quinquenel A et al. Blood. 2019 Jun 26. doi: 10.1182/blood.2019000854.

Mutations in Bruton’s tyrosine kinase (BTK) are associated with progression of chronic lymphocytic leukemia (CLL) in patients taking ibrutinib, according to a new study.

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

Researchers analyzed a “real-life” cohort of CLL patients taking ibrutinib for about 3 years and found that patients with BTK mutations were significantly more likely to progress (P = .0005).

“Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment,” wrote Anne Quinquenel, MD, PhD, of Hôpital Robert Debré, Université Reims (France) Champagne-Ardenne, and colleagues. Their report is in Blood.

The researchers studied 57 CLL patients who were still on ibrutinib after at least 3 years and provided fresh blood samples. The median time between the start of ibrutinib and sample collection was 3.5 years.

All 57 patients had minimal residual disease at baseline. Of the 55 patients with response data available, 48 had a partial response, and 7 had a partial response with lymphocytosis.

Mutational profiling was possible in 30 patients who had a CLL clone greater than or equal to 0.5 x 10⁹/L.

BTK mutations were present in 17 of the 30 patients (57%). There were 20 BTK mutations in total, all were at C481, and 14 were at C481S.

The researchers also identified 15 patients with TP53 mutations and 4 patients with phospholipase Cg2 (PLCG2) mutations. All 4 patients with PLCG2 mutations also had a BTK mutation and a TP53 mutation.

However, there were no significant associations between BTK mutations and other mutations. BTK mutations were not associated with the number of previous therapies a patient received or the need for ibrutinib dose interruptions or reductions.

The researchers assessed CLL progression at median of 8.5 months from sample collection and found the presence of a BTK mutation was significantly associated with progression (P = .0005).

Of the 17 patients with a BTK mutation, 14 progressed with one case of Richter’s syndrome. Three patients who progressed were still on ibrutinib, nine patients received venetoclax, and two patients died without further treatment.

Of the 13 patients without BTK mutations, just two patients progressed. One patient died without further treatment, and the other received venetoclax.

The event-free survival was significantly shorter in patients with a BTK mutation than in those without (P = .0380), but there was no significant difference in overall survival.

This research was supported by Sunesis Pharmaceuticals and the Force Hemato (fonds de recherche clinique en hématologie) foundation. The researchers reported relationships with Janssen, Gilead, Roche, and AbbVie.

[email protected]

SOURCE: Quinquenel A et al. Blood. 2019 Jun 26. doi: 10.1182/blood.2019000854.

The strategy of simultaneously inhibiting proliferation and reactivating apoptosis can eradicate chronic lymphocytic leukemia (CLL) in a large share of patients, suggest results from the phase 2 CLARITY trial.

©Ed Uthman/Flickr

“Both ibrutinib and venetoclax are active in CLL with improved survival; however, as monotherapies, both currently are given until disease progression,” wrote Peter Hillmen, MBChB, PhD, St. James’s University Hospital, Leeds, England, and his colleagues.

In the single-arm, open-label trial, the investigators treated 53 patients with relapsed or refractory CLL with combination ibrutinib (Imbruvica), a small-molecule inhibitor of Bruton’s tyrosine kinase, and venetoclax (Venclexta), a small molecule inhibitor of the anti-apoptotic protein Bcl-2. The primary endpoint was MRD negativity, defined as presence of fewer than one CLL cell in 10,000 leukocytes, after 12 months of combination therapy.

Results reported in the Journal of Clinical Oncology showed that the combination was highly active, with 53% of patients achieving MRD negativity in the blood and 36% achieving MRD negativity in the marrow.

Most patients, 89%, had a treatment response, and slightly more than half, 51%, achieved a complete remission. With a median 21.1-month follow-up, only a single patient experienced progression and all were still alive.

Adverse effects were generally manageable. Grade 3-4 adverse events of special interest included 34 cases of neutropenia and 1 case of biochemical tumor lysis syndrome that was managed by delaying venetoclax.

“We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects,” the investigators wrote. “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission.”


Whether the combination leads to permanent disease eradication in certain patients is still unclear, the investigators added.

The trial was supported by Bloodwise under the Trials Acceleration Programme, by the National Institute for Health Research Leeds Clinical Research Facility, and by an unrestricted educational grant from Janssen-Cilag and AbbVie. Ibrutinib was provided free of charge by Janssen-Cilag, and venetoclax was provided free of charge by AbbVie. Dr. Hillman reported financial relationships with Janssen, AbbVie, Roche, Pharmacyclics, and Gilead Sciences.

SOURCE: Hillmen P et al. J Clin Oncol. 2019 Jul 11. doi: 10.1200/JCO.19.00894.

The strategy of simultaneously inhibiting proliferation and reactivating apoptosis can eradicate chronic lymphocytic leukemia (CLL) in a large share of patients, suggest results from the phase 2 CLARITY trial.

©Ed Uthman/Flickr

“Both ibrutinib and venetoclax are active in CLL with improved survival; however, as monotherapies, both currently are given until disease progression,” wrote Peter Hillmen, MBChB, PhD, St. James’s University Hospital, Leeds, England, and his colleagues.

In the single-arm, open-label trial, the investigators treated 53 patients with relapsed or refractory CLL with combination ibrutinib (Imbruvica), a small-molecule inhibitor of Bruton’s tyrosine kinase, and venetoclax (Venclexta), a small molecule inhibitor of the anti-apoptotic protein Bcl-2. The primary endpoint was MRD negativity, defined as presence of fewer than one CLL cell in 10,000 leukocytes, after 12 months of combination therapy.

Results reported in the Journal of Clinical Oncology showed that the combination was highly active, with 53% of patients achieving MRD negativity in the blood and 36% achieving MRD negativity in the marrow.

Most patients, 89%, had a treatment response, and slightly more than half, 51%, achieved a complete remission. With a median 21.1-month follow-up, only a single patient experienced progression and all were still alive.

Adverse effects were generally manageable. Grade 3-4 adverse events of special interest included 34 cases of neutropenia and 1 case of biochemical tumor lysis syndrome that was managed by delaying venetoclax.

“We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects,” the investigators wrote. “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission.”


Whether the combination leads to permanent disease eradication in certain patients is still unclear, the investigators added.

The trial was supported by Bloodwise under the Trials Acceleration Programme, by the National Institute for Health Research Leeds Clinical Research Facility, and by an unrestricted educational grant from Janssen-Cilag and AbbVie. Ibrutinib was provided free of charge by Janssen-Cilag, and venetoclax was provided free of charge by AbbVie. Dr. Hillman reported financial relationships with Janssen, AbbVie, Roche, Pharmacyclics, and Gilead Sciences.

SOURCE: Hillmen P et al. J Clin Oncol. 2019 Jul 11. doi: 10.1200/JCO.19.00894.

The strategy of simultaneously inhibiting proliferation and reactivating apoptosis can eradicate chronic lymphocytic leukemia (CLL) in a large share of patients, suggest results from the phase 2 CLARITY trial.

©Ed Uthman/Flickr

“Both ibrutinib and venetoclax are active in CLL with improved survival; however, as monotherapies, both currently are given until disease progression,” wrote Peter Hillmen, MBChB, PhD, St. James’s University Hospital, Leeds, England, and his colleagues.

In the single-arm, open-label trial, the investigators treated 53 patients with relapsed or refractory CLL with combination ibrutinib (Imbruvica), a small-molecule inhibitor of Bruton’s tyrosine kinase, and venetoclax (Venclexta), a small molecule inhibitor of the anti-apoptotic protein Bcl-2. The primary endpoint was MRD negativity, defined as presence of fewer than one CLL cell in 10,000 leukocytes, after 12 months of combination therapy.

Results reported in the Journal of Clinical Oncology showed that the combination was highly active, with 53% of patients achieving MRD negativity in the blood and 36% achieving MRD negativity in the marrow.

Most patients, 89%, had a treatment response, and slightly more than half, 51%, achieved a complete remission. With a median 21.1-month follow-up, only a single patient experienced progression and all were still alive.

Adverse effects were generally manageable. Grade 3-4 adverse events of special interest included 34 cases of neutropenia and 1 case of biochemical tumor lysis syndrome that was managed by delaying venetoclax.

“We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects,” the investigators wrote. “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission.”


Whether the combination leads to permanent disease eradication in certain patients is still unclear, the investigators added.

The trial was supported by Bloodwise under the Trials Acceleration Programme, by the National Institute for Health Research Leeds Clinical Research Facility, and by an unrestricted educational grant from Janssen-Cilag and AbbVie. Ibrutinib was provided free of charge by Janssen-Cilag, and venetoclax was provided free of charge by AbbVie. Dr. Hillman reported financial relationships with Janssen, AbbVie, Roche, Pharmacyclics, and Gilead Sciences.

SOURCE: Hillmen P et al. J Clin Oncol. 2019 Jul 11. doi: 10.1200/JCO.19.00894.

Researchers have characterized the clinical presentation, progression, and prognosis of leukemia cutis in a pediatric population, according to findings from a retrospective case series.

“To our knowledge, this is the largest reported case series of pediatric leukemia cutis,” wrote Elena Corina Andriescu of the University of Texas, Houston, and colleagues. The results were published in Pediatric Dermatology.

The study included 31 children with histologically confirmed leukemia cutis at one of two pediatric institutions. The researchers reviewed medical records to distinguish common features among patients.

Various clinical data, including disease subtype, related symptoms, management, and prognosis, were collected from January 1993 to March 2014. The children in the case series ranged in age up to 19 years with a median age at diagnosis of 26.8 months.

After analysis, the researchers reported that the magnitude and morphology of disease lesions differed among pediatric patients, with the most common sites being the lower extremities and head. The most common morphologies were nodules and papules. Additionally, the researchers found that lesions were often erythematous, violaceous, or both colors.

The majority of patients (65%) presented with concomitant systemic leukemia and leukemia cutis. The most common types of leukemia associated with the skin condition were acute myeloid leukemia (in 74% of cases) and acute lymphoblastic leukemia (in 16% of cases). The researchers saw no significant differences in leukemia cutis morphology or distribution based on the leukemia diagnosis.

“Most cases of leukemia cutis arose during initial leukemia episodes, rather than with relapsed leukemia,” they added.

Because of an insufficiency of specific genetic data, investigators were unable to make prognostic inferences in the majority of participants.

Two key limitations of the study were the small sample size and retrospective design. As a result, the investigators were unable to prospectively classify skin findings in a systematic manner. Despite these limitations, the authors noted that these findings add to the present knowledge of leukemia cutis in pediatric patients.

“Importantly, the presence of [leukemia cutis] changed the management of systemic leukemia in one‐third of patients,” the researchers wrote. “The potential for major changes in treatment plans such as adding radiation therapy and deferring hematopoietic stem cell transplantation underscores the importance of diagnosing [leukemia cutis].”

No funding sources were reported. The authors did not report conflicts of interest.

SOURCE: Andriescu EC et al. Pediatr Dermatol. 2019 Jul 5. doi: 10.1111/pde.13864.

Researchers have characterized the clinical presentation, progression, and prognosis of leukemia cutis in a pediatric population, according to findings from a retrospective case series.

“To our knowledge, this is the largest reported case series of pediatric leukemia cutis,” wrote Elena Corina Andriescu of the University of Texas, Houston, and colleagues. The results were published in Pediatric Dermatology.

The study included 31 children with histologically confirmed leukemia cutis at one of two pediatric institutions. The researchers reviewed medical records to distinguish common features among patients.

Various clinical data, including disease subtype, related symptoms, management, and prognosis, were collected from January 1993 to March 2014. The children in the case series ranged in age up to 19 years with a median age at diagnosis of 26.8 months.

After analysis, the researchers reported that the magnitude and morphology of disease lesions differed among pediatric patients, with the most common sites being the lower extremities and head. The most common morphologies were nodules and papules. Additionally, the researchers found that lesions were often erythematous, violaceous, or both colors.

The majority of patients (65%) presented with concomitant systemic leukemia and leukemia cutis. The most common types of leukemia associated with the skin condition were acute myeloid leukemia (in 74% of cases) and acute lymphoblastic leukemia (in 16% of cases). The researchers saw no significant differences in leukemia cutis morphology or distribution based on the leukemia diagnosis.

“Most cases of leukemia cutis arose during initial leukemia episodes, rather than with relapsed leukemia,” they added.

Because of an insufficiency of specific genetic data, investigators were unable to make prognostic inferences in the majority of participants.

Two key limitations of the study were the small sample size and retrospective design. As a result, the investigators were unable to prospectively classify skin findings in a systematic manner. Despite these limitations, the authors noted that these findings add to the present knowledge of leukemia cutis in pediatric patients.

“Importantly, the presence of [leukemia cutis] changed the management of systemic leukemia in one‐third of patients,” the researchers wrote. “The potential for major changes in treatment plans such as adding radiation therapy and deferring hematopoietic stem cell transplantation underscores the importance of diagnosing [leukemia cutis].”

No funding sources were reported. The authors did not report conflicts of interest.

SOURCE: Andriescu EC et al. Pediatr Dermatol. 2019 Jul 5. doi: 10.1111/pde.13864.

Researchers have characterized the clinical presentation, progression, and prognosis of leukemia cutis in a pediatric population, according to findings from a retrospective case series.

“To our knowledge, this is the largest reported case series of pediatric leukemia cutis,” wrote Elena Corina Andriescu of the University of Texas, Houston, and colleagues. The results were published in Pediatric Dermatology.

The study included 31 children with histologically confirmed leukemia cutis at one of two pediatric institutions. The researchers reviewed medical records to distinguish common features among patients.

Various clinical data, including disease subtype, related symptoms, management, and prognosis, were collected from January 1993 to March 2014. The children in the case series ranged in age up to 19 years with a median age at diagnosis of 26.8 months.

After analysis, the researchers reported that the magnitude and morphology of disease lesions differed among pediatric patients, with the most common sites being the lower extremities and head. The most common morphologies were nodules and papules. Additionally, the researchers found that lesions were often erythematous, violaceous, or both colors.

The majority of patients (65%) presented with concomitant systemic leukemia and leukemia cutis. The most common types of leukemia associated with the skin condition were acute myeloid leukemia (in 74% of cases) and acute lymphoblastic leukemia (in 16% of cases). The researchers saw no significant differences in leukemia cutis morphology or distribution based on the leukemia diagnosis.

“Most cases of leukemia cutis arose during initial leukemia episodes, rather than with relapsed leukemia,” they added.

Because of an insufficiency of specific genetic data, investigators were unable to make prognostic inferences in the majority of participants.

Two key limitations of the study were the small sample size and retrospective design. As a result, the investigators were unable to prospectively classify skin findings in a systematic manner. Despite these limitations, the authors noted that these findings add to the present knowledge of leukemia cutis in pediatric patients.

“Importantly, the presence of [leukemia cutis] changed the management of systemic leukemia in one‐third of patients,” the researchers wrote. “The potential for major changes in treatment plans such as adding radiation therapy and deferring hematopoietic stem cell transplantation underscores the importance of diagnosing [leukemia cutis].”

No funding sources were reported. The authors did not report conflicts of interest.

SOURCE: Andriescu EC et al. Pediatr Dermatol. 2019 Jul 5. doi: 10.1111/pde.13864.