Indolent Lymphoma

ATLANTA – Zanubrutinib (BGB-3111), an investigational BTK inhibitor, was well tolerated and active as a single agent in patients with indolent and aggressive forms of non-Hodgkin lymphoma, according to data presented at the annual meeting of the American Society of Hematology.

Response rates ranged from 31% to 88% depending on the lymphoma subtype. Overall, approximately 10% of patients discontinued the drug because of adverse events, reported Constantine S. Tam, MBBS, MD, of Peter MacCallum Cancer Centre & St. Vincent’s Hospital, Melbourne.

“There was encouraging activity against all the spectrum of indolent and aggressive NHL subtypes … and durable responses were observed across a variety of histologies,” Dr. Tam said.

Zanubrutinib is a second-generation BTK inhibitor that, based on biochemical assays, has higher selectivity against BTK than ibrutinib, Dr. Tam said.

He presented results of an open-label, multicenter, phase 1b study of daily or twice-daily zanubrutinib in patients with B-cell malignancies, most of them relapsed or refractory to prior therapies. The lymphoma subtypes he presented included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL).

For 34 patients with indolent lymphomas (FL and MZL), the most frequent adverse events were petechiae/purpura/contusion and upper respiratory tract infection. Eleven grade 3-5 adverse events were reported, including neutropenia, infection, nausea, urinary tract infection, and abdominal pain.

Atrial fibrillation was observed in two patients in the aggressive NHL cohort, for an overall AF rate of approximately 2%, Dr. Tam said.

For 65 patients with aggressive lymphomas (DLBCL and MCL), the most frequent adverse events were petechiae/purpura/contusion and diarrhea; 27 grade 3-5 adverse events were reported, including neutropenia, pneumonia, and anemia.

The highest overall response rate reported was for MCL, at 88% (28 of 32 patients) followed by MZL at 78% (7 of 9 patients), FL at 41% (7 of 17 patients), and DLBCL 31% (8 of 26 patients).

The recommended phase 2 dose for zanubrutinib is either 320 mg/day once daily or a split dose of 160 mg twice daily, Dr. Tam said.

Based on this experience, investigators started a registration trial of zanubrutinib in combination with obinutuzumab for FL, and additional trials are planned, according to Dr. Tam.

There are also registration trials in Waldenstrom macroglobulinemia and chronic lymphocytic leukemia based on other data suggesting activity of zanubrutinib in those disease types, he added.

Zanubrutinib is a product of BeiGene. Dr. Tam reported disclosures related to Roche, Janssen Cilag, Abbvie, Celgene, Pharmacyclics, Onyx, and Amgen.

SOURCE: Tam C et al, ASH 2017, Abstract 152

ATLANTA – Zanubrutinib (BGB-3111), an investigational BTK inhibitor, was well tolerated and active as a single agent in patients with indolent and aggressive forms of non-Hodgkin lymphoma, according to data presented at the annual meeting of the American Society of Hematology.

Response rates ranged from 31% to 88% depending on the lymphoma subtype. Overall, approximately 10% of patients discontinued the drug because of adverse events, reported Constantine S. Tam, MBBS, MD, of Peter MacCallum Cancer Centre & St. Vincent’s Hospital, Melbourne.

“There was encouraging activity against all the spectrum of indolent and aggressive NHL subtypes … and durable responses were observed across a variety of histologies,” Dr. Tam said.

Zanubrutinib is a second-generation BTK inhibitor that, based on biochemical assays, has higher selectivity against BTK than ibrutinib, Dr. Tam said.

He presented results of an open-label, multicenter, phase 1b study of daily or twice-daily zanubrutinib in patients with B-cell malignancies, most of them relapsed or refractory to prior therapies. The lymphoma subtypes he presented included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL).

For 34 patients with indolent lymphomas (FL and MZL), the most frequent adverse events were petechiae/purpura/contusion and upper respiratory tract infection. Eleven grade 3-5 adverse events were reported, including neutropenia, infection, nausea, urinary tract infection, and abdominal pain.

Atrial fibrillation was observed in two patients in the aggressive NHL cohort, for an overall AF rate of approximately 2%, Dr. Tam said.

For 65 patients with aggressive lymphomas (DLBCL and MCL), the most frequent adverse events were petechiae/purpura/contusion and diarrhea; 27 grade 3-5 adverse events were reported, including neutropenia, pneumonia, and anemia.

The highest overall response rate reported was for MCL, at 88% (28 of 32 patients) followed by MZL at 78% (7 of 9 patients), FL at 41% (7 of 17 patients), and DLBCL 31% (8 of 26 patients).

The recommended phase 2 dose for zanubrutinib is either 320 mg/day once daily or a split dose of 160 mg twice daily, Dr. Tam said.

Based on this experience, investigators started a registration trial of zanubrutinib in combination with obinutuzumab for FL, and additional trials are planned, according to Dr. Tam.

There are also registration trials in Waldenstrom macroglobulinemia and chronic lymphocytic leukemia based on other data suggesting activity of zanubrutinib in those disease types, he added.

Zanubrutinib is a product of BeiGene. Dr. Tam reported disclosures related to Roche, Janssen Cilag, Abbvie, Celgene, Pharmacyclics, Onyx, and Amgen.

SOURCE: Tam C et al, ASH 2017, Abstract 152

ATLANTA – Zanubrutinib (BGB-3111), an investigational BTK inhibitor, was well tolerated and active as a single agent in patients with indolent and aggressive forms of non-Hodgkin lymphoma, according to data presented at the annual meeting of the American Society of Hematology.

Response rates ranged from 31% to 88% depending on the lymphoma subtype. Overall, approximately 10% of patients discontinued the drug because of adverse events, reported Constantine S. Tam, MBBS, MD, of Peter MacCallum Cancer Centre & St. Vincent’s Hospital, Melbourne.

“There was encouraging activity against all the spectrum of indolent and aggressive NHL subtypes … and durable responses were observed across a variety of histologies,” Dr. Tam said.

Zanubrutinib is a second-generation BTK inhibitor that, based on biochemical assays, has higher selectivity against BTK than ibrutinib, Dr. Tam said.

He presented results of an open-label, multicenter, phase 1b study of daily or twice-daily zanubrutinib in patients with B-cell malignancies, most of them relapsed or refractory to prior therapies. The lymphoma subtypes he presented included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL).

For 34 patients with indolent lymphomas (FL and MZL), the most frequent adverse events were petechiae/purpura/contusion and upper respiratory tract infection. Eleven grade 3-5 adverse events were reported, including neutropenia, infection, nausea, urinary tract infection, and abdominal pain.

Atrial fibrillation was observed in two patients in the aggressive NHL cohort, for an overall AF rate of approximately 2%, Dr. Tam said.

For 65 patients with aggressive lymphomas (DLBCL and MCL), the most frequent adverse events were petechiae/purpura/contusion and diarrhea; 27 grade 3-5 adverse events were reported, including neutropenia, pneumonia, and anemia.

The highest overall response rate reported was for MCL, at 88% (28 of 32 patients) followed by MZL at 78% (7 of 9 patients), FL at 41% (7 of 17 patients), and DLBCL 31% (8 of 26 patients).

The recommended phase 2 dose for zanubrutinib is either 320 mg/day once daily or a split dose of 160 mg twice daily, Dr. Tam said.

Based on this experience, investigators started a registration trial of zanubrutinib in combination with obinutuzumab for FL, and additional trials are planned, according to Dr. Tam.

There are also registration trials in Waldenstrom macroglobulinemia and chronic lymphocytic leukemia based on other data suggesting activity of zanubrutinib in those disease types, he added.

Zanubrutinib is a product of BeiGene. Dr. Tam reported disclosures related to Roche, Janssen Cilag, Abbvie, Celgene, Pharmacyclics, Onyx, and Amgen.

SOURCE: Tam C et al, ASH 2017, Abstract 152

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

ATLANTA – Waldenström macroglobulinemia can present as acquired von Willebrand disease (VWD), and when it does, the finding strongly correlates with high serum IgM levels and the presence of CXCR4 mutations, according to the results of a large, single-center retrospective study.

Further, successfully treating Waldenström macroglobulinemia often resolves acquired VWD, and the depth of treatment response predicts the degree of improvement, Jorge J. Castillo, MD, and his associates wrote in a poster presented at the annual meeting of the American Society of Hematology.

Acquired VWD is an uncommon, poorly understood presentation of Waldenström macroglobulinemia. Because affected patients require treatment, better characterizing this subgroup is important, the investigators noted.

At the Bing Center for Waldenström Macroglobulinemia at Dana-Farber Cancer Institute in Boston, the researchers retrospectively studied 320 individuals with newly diagnosed Waldenström macroglobulinemia and used logistic regression analysis to seek predictors of acquired VWD, which they evaluated by measuring levels of VW factor antigen, VW factor activity, and factor VIII. Levels under 30% were considered VWD and levels between 30% and 50% were considered low-level VWD.

In all, 49 individuals had acquired VWD while 271 patients did not. These two groups were similar in terms of age, sex, hemoglobin level, platelet count, and bone marrow involvement. However, 45% of patients with acquired VWD had serum IgM levels above 6,000 mg/dL versus 6% of patients without acquired VWD (P less than .001), and 47% of patients with acquired VWD had serum IgM levels between 3,000 and 5,999 versus 31% of patients without acquired VWD (P less than .001). Also, 77% of patients with acquired VWD tested positive for CXCR4 mutation versus 37% of patients without acquired VWD (P less than .001).

A significantly higher proportion of patients without acquired VWD had white blood cell concentrations above 6,000/mcL (29% vs. 50%; P = .006). This finding lost statistical significance in the logistic regression model, but all the other variables remained significantly associated. Serum IgM levels above 6,000 mg/dL conferred a 55-fold increase in the odds of having acquired VWD (95% confidence interval, 17-177; P less than .001), and serum IgM levels between 3,000 and 5,999 mg/dL led to an 11-fold increase in these odds (95% CI, 4-34). The presence of CXCR4 mutations was associated with a sixfold increased odds of acquired VWD (95% CI, 2-15). The P value for each of these three associations was at or below .001.

Therapy for Waldenström macroglobulinemia led to statistically significant increases in levels of factor VIII, VW factor antigen, and VW factor activity (P less than .001) and the median of each level improved by at least 35% after treatment. After treatment, 78% of patients with acquired VWD had levels of all three measures above 50% (versus 0% before treatment; P less than .001). Patients with acquired VWD with the best responses to treatment had about a 90% decrease in IgM levels, while those with a partial response had about a two-thirds decrease and patients with stable disease had about a 20% decrease. A linear regression model confirmed that depth of treatment response, based on change in IgM level, correlated with degree of improvement in VWD – that is, the extent of improvement in levels of VW factor antigen, VW factor activity, and factor VIII.

No external funding sources were reported. Dr. Castillo disclosed consulting ties and research funding from Pharmacyclics and Janssen, and research funding from Millenium and Abbvie.

SOURCE: Castillo J, et al. ASH 2017 Abstract 1088.

ATLANTA – Waldenström macroglobulinemia can present as acquired von Willebrand disease (VWD), and when it does, the finding strongly correlates with high serum IgM levels and the presence of CXCR4 mutations, according to the results of a large, single-center retrospective study.

Further, successfully treating Waldenström macroglobulinemia often resolves acquired VWD, and the depth of treatment response predicts the degree of improvement, Jorge J. Castillo, MD, and his associates wrote in a poster presented at the annual meeting of the American Society of Hematology.

Acquired VWD is an uncommon, poorly understood presentation of Waldenström macroglobulinemia. Because affected patients require treatment, better characterizing this subgroup is important, the investigators noted.

At the Bing Center for Waldenström Macroglobulinemia at Dana-Farber Cancer Institute in Boston, the researchers retrospectively studied 320 individuals with newly diagnosed Waldenström macroglobulinemia and used logistic regression analysis to seek predictors of acquired VWD, which they evaluated by measuring levels of VW factor antigen, VW factor activity, and factor VIII. Levels under 30% were considered VWD and levels between 30% and 50% were considered low-level VWD.

In all, 49 individuals had acquired VWD while 271 patients did not. These two groups were similar in terms of age, sex, hemoglobin level, platelet count, and bone marrow involvement. However, 45% of patients with acquired VWD had serum IgM levels above 6,000 mg/dL versus 6% of patients without acquired VWD (P less than .001), and 47% of patients with acquired VWD had serum IgM levels between 3,000 and 5,999 versus 31% of patients without acquired VWD (P less than .001). Also, 77% of patients with acquired VWD tested positive for CXCR4 mutation versus 37% of patients without acquired VWD (P less than .001).

A significantly higher proportion of patients without acquired VWD had white blood cell concentrations above 6,000/mcL (29% vs. 50%; P = .006). This finding lost statistical significance in the logistic regression model, but all the other variables remained significantly associated. Serum IgM levels above 6,000 mg/dL conferred a 55-fold increase in the odds of having acquired VWD (95% confidence interval, 17-177; P less than .001), and serum IgM levels between 3,000 and 5,999 mg/dL led to an 11-fold increase in these odds (95% CI, 4-34). The presence of CXCR4 mutations was associated with a sixfold increased odds of acquired VWD (95% CI, 2-15). The P value for each of these three associations was at or below .001.

Therapy for Waldenström macroglobulinemia led to statistically significant increases in levels of factor VIII, VW factor antigen, and VW factor activity (P less than .001) and the median of each level improved by at least 35% after treatment. After treatment, 78% of patients with acquired VWD had levels of all three measures above 50% (versus 0% before treatment; P less than .001). Patients with acquired VWD with the best responses to treatment had about a 90% decrease in IgM levels, while those with a partial response had about a two-thirds decrease and patients with stable disease had about a 20% decrease. A linear regression model confirmed that depth of treatment response, based on change in IgM level, correlated with degree of improvement in VWD – that is, the extent of improvement in levels of VW factor antigen, VW factor activity, and factor VIII.

No external funding sources were reported. Dr. Castillo disclosed consulting ties and research funding from Pharmacyclics and Janssen, and research funding from Millenium and Abbvie.

SOURCE: Castillo J, et al. ASH 2017 Abstract 1088.

ATLANTA – Waldenström macroglobulinemia can present as acquired von Willebrand disease (VWD), and when it does, the finding strongly correlates with high serum IgM levels and the presence of CXCR4 mutations, according to the results of a large, single-center retrospective study.

Further, successfully treating Waldenström macroglobulinemia often resolves acquired VWD, and the depth of treatment response predicts the degree of improvement, Jorge J. Castillo, MD, and his associates wrote in a poster presented at the annual meeting of the American Society of Hematology.

Acquired VWD is an uncommon, poorly understood presentation of Waldenström macroglobulinemia. Because affected patients require treatment, better characterizing this subgroup is important, the investigators noted.

At the Bing Center for Waldenström Macroglobulinemia at Dana-Farber Cancer Institute in Boston, the researchers retrospectively studied 320 individuals with newly diagnosed Waldenström macroglobulinemia and used logistic regression analysis to seek predictors of acquired VWD, which they evaluated by measuring levels of VW factor antigen, VW factor activity, and factor VIII. Levels under 30% were considered VWD and levels between 30% and 50% were considered low-level VWD.

In all, 49 individuals had acquired VWD while 271 patients did not. These two groups were similar in terms of age, sex, hemoglobin level, platelet count, and bone marrow involvement. However, 45% of patients with acquired VWD had serum IgM levels above 6,000 mg/dL versus 6% of patients without acquired VWD (P less than .001), and 47% of patients with acquired VWD had serum IgM levels between 3,000 and 5,999 versus 31% of patients without acquired VWD (P less than .001). Also, 77% of patients with acquired VWD tested positive for CXCR4 mutation versus 37% of patients without acquired VWD (P less than .001).

A significantly higher proportion of patients without acquired VWD had white blood cell concentrations above 6,000/mcL (29% vs. 50%; P = .006). This finding lost statistical significance in the logistic regression model, but all the other variables remained significantly associated. Serum IgM levels above 6,000 mg/dL conferred a 55-fold increase in the odds of having acquired VWD (95% confidence interval, 17-177; P less than .001), and serum IgM levels between 3,000 and 5,999 mg/dL led to an 11-fold increase in these odds (95% CI, 4-34). The presence of CXCR4 mutations was associated with a sixfold increased odds of acquired VWD (95% CI, 2-15). The P value for each of these three associations was at or below .001.

Therapy for Waldenström macroglobulinemia led to statistically significant increases in levels of factor VIII, VW factor antigen, and VW factor activity (P less than .001) and the median of each level improved by at least 35% after treatment. After treatment, 78% of patients with acquired VWD had levels of all three measures above 50% (versus 0% before treatment; P less than .001). Patients with acquired VWD with the best responses to treatment had about a 90% decrease in IgM levels, while those with a partial response had about a two-thirds decrease and patients with stable disease had about a 20% decrease. A linear regression model confirmed that depth of treatment response, based on change in IgM level, correlated with degree of improvement in VWD – that is, the extent of improvement in levels of VW factor antigen, VW factor activity, and factor VIII.

No external funding sources were reported. Dr. Castillo disclosed consulting ties and research funding from Pharmacyclics and Janssen, and research funding from Millenium and Abbvie.

SOURCE: Castillo J, et al. ASH 2017 Abstract 1088.

Waldenstrom disease, also known as Waldenstrom macroglobulinemia, has been linked to a rare bilateral facial nerve palsy in a second case report.

Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.

Michail Charakidis, David Joseph Russell/Wikimedia Commons/CC BY 2.0

SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.

Waldenstrom disease, also known as Waldenstrom macroglobulinemia, has been linked to a rare bilateral facial nerve palsy in a second case report.

Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.

Michail Charakidis, David Joseph Russell/Wikimedia Commons/CC BY 2.0

SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.

Waldenstrom disease, also known as Waldenstrom macroglobulinemia, has been linked to a rare bilateral facial nerve palsy in a second case report.

Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.

Michail Charakidis, David Joseph Russell/Wikimedia Commons/CC BY 2.0

SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.

For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.

Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.

The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.

Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.

“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.

Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.

However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.

“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.

Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.

Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.

Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.

The researchers reported having no relevant financial disclosures.

SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.

For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.

Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.

The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.

Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.

“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.

Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.

However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.

“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.

Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.

Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.

Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.

The researchers reported having no relevant financial disclosures.

SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.

For patients with splenic marginal zone lymphoma (MZL) requiring treatment, rituximab may be a superior choice, compared with splenectomy, according to authors of a recent review article.

Although treatment with splenectomy and rituximab both are associated with high rates of 10-year survival, splenectomy also is associated with acute surgical complications and late toxicities, mainly from infections, Christina Kalpadakis, MD, of the department of hematology at Heraklion University Hospital, University of Crete, Greece, reported in Best Practice & Research Clinical Haematology.

The review article aims to answer the question of whether rituximab monotherapy should replace splenectomy as the treatment of choice, according to the authors, who said treatment for this rare, low-grade B-cell lymphoma has not been standardized due to a lack of large, randomized trials.

Asymptomatic splenic MZL without significant cytopenias can be managed with a watch-and-wait approach, but when treatment is warranted, the choice is often between splenectomy, rituximab monotherapy, or chemoimmunotherapy.

“Based on the existing retrospective series of patients, rituximab monotherapy appears to be the best choice since it combines high efficacy with the lowest toxicity,” Dr. Kalpadakis and her colleagues wrote.

Until the early 2000s, splenectomy was the standard treatment modality for splenic MZL, offering quick amelioration of symptoms related to splenomegaly in more than 90% of patients, as well as improvements in hypersplenism-related cytopenias, the researchers reported. Among 100 patients with splenic MZL, the median progression-free survival with splenectomy was 8.25 years, and median 10-year overall survival was 67%.

However, responses to splenectomy are not complete because some patients are not good candidates for splenectomy, including those with lymphadenopathy or heavy bone marrow infiltration, according to the authors. Moreover, since it is a major surgical procedure that can be associated with complications and infections, splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk, they wrote.

“Furthermore, splenectomy cannot eradicate bone marrow disease and has no impact on other extrasplenic disease localization such as lymphadenopathy,” they added.

Rituximab monotherapy, by contrast, has “minimal toxicity” with high efficacy, including complete response rates of around 50% and a 10-year overall survival of 85% reported in a series of 104 patients.

Maintenance with rituximab may further improve the quality of responses, although data are limited. One study, conducted by the review article authors, showed that rituximab maintenance increased the complete response rate from 42% after induction treatment to 71% after maintenance, along with a significant improvement in response duration, though no differences in overall survival have been observed thus far.

Rituximab plus chemotherapy has been evaluated, but with “significant toxicity without improvement in the outcome” versus rituximab monotherapy, the researchers wrote. Splenectomy is “effective” but should be reserved for patients refractory to rituximab, Dr. Kalpadakis and her colleagues wrote.

The researchers reported having no relevant financial disclosures.

SOURCE: Kalpadakis C et al. Best Pract Res Clin Haematol. Mar-Jun 2017. doi:10.1016/j.beha.2017.10.011.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

ATLANTA – More than one-third of patients with refractory large B-cell lymphomas treated with the chimeric antigen receptor (CAR) T-cell product axicabtagene ciloleucel (Yescarta), often called axi-cel, had durable responses, with some patients having complete responses lasting more than 1 year after a single infusion, according to investigators in the ZUMA-1 trial.

Neil Osterweil/Frontline Medical News

Updated combined phase 1 and phase 2 results in 108 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) showed an objective response rate (ORR) of 82%, including 58% complete responses, after a median follow-up of 15.4 months, reported Sattva S. Neelapu, MD, from the University of Texas MD Anderson Cancer Center in Houston.

“Axi-cel is highly effective in patients with large B-cell lymphoma who otherwise have no curative treatment options,” he said in a briefing at the annual meeting of the American Society of Hematology, prior to his presentation of the data in an oral session.

The trial results were also published simultaneously in the New England Journal of Medicine.As previously reported, in the multicenter phase 2 ZUMA-1 trial, 111 patients with treatment refractory DLBCL, PMBCL, or TFL were enrolled and treated with axi-cel at a target dose of 2 x 10⁶ cells/kg, following a conditioning regimen with low-dose cyclophosphamide and fludarabine.

The median patient age was 58 years. Patients had stage III or IV disease, 48% had International Prognostic Index scores of 3-4, 76% had disease that was refractory to third-line therapies or beyond, and 21% had disease that relapsed within 12 months of an autologous bone marrow transplant

Axi-cel was successfully manufactured with sufficient cells for transfusion in all but one of the 111 patients, and 101 patients eventually received infusions in phase 2 (modified intention-to-treat population). The average turnaround time from apheresis to the clinical site was 17 days.

Dr. Neelapu also presented data on seven patients enrolled in phase 1; the data were combined with the phase 2 results for an updated analysis of those patients who had at least 1 year of follow-up.

The phase 2 trial met its primary endpoint at the time of the primary analysis, with an 82% ORR, consisting of 54% complete responses and 28% partial responses at a median follow-up of 8.7 months.

In the updated analysis, the ORR and respective remission rates were 82%, 58%, and 34%, at a median of 15.4 months follow-up.

The median duration of response in the updated analysis was 11.1 months. The median duration of complete responses had not been reached at the time of data cutoff in August 2017. The median duration of partial responses was 1.9 months.

At the 15.4-month mark, 42% of patients remained free of disease progression, and 56% were alive, with the median overall survival not yet reached.

The treatment had generally acceptable toxicities, with only 13% of patients in phase 2 experiencing grade 3 or greater cytokine release syndrome (CRS), although one patient with CRS died from hemophagocytic lymphohistiocytosis, and one with CRS died from cardiac arrest. Grade 3 or greater neurologic events occurred in 28% of patients, and included encephalopathy, confusional state, aphasia, and somnolence.

The events were generally reversible, and the rates of each declined over time. The use of tocilizumab or steroids to control adverse events did not have a negative effect on responses.

Since the primary analysis with at least 6 months of follow-up, there have been no new axi-cel–related cases of CRS, neurologic events, or deaths.

Dr. Neelapu also presented safety data on serious adverse events occurring more than 6 months after therapy in 10 patients who developed symptoms after the data cutoff.

Grade 3 events in these patients included lung infection, recurrent upper respiratory viral infection, and rotavirus infection, pneumonias, atrial fibrillation with rapid ventricular response, lung infection, febrile neutropenia, and influenza B infection. One patient had grade 4 sepsis.

In an editorial accompanying the study in the New England Journal of Medicine, Eric Tran, PhD, and Walter J. Urba, MD, PhD, from the Earle A. Chiles Research Institute and the Providence Portland (Ore.) Medical Center, and Dan L. Longo, MD, deputy editor of the journal, praised ZUMA-1 as “a landmark study because it involved 22 institutions and showed that a personalized gene-engineered T-cell product could be rapidly generated at a centralized cell-manufacturing facility and safely administered to patients at transplantation-capable medical centers.”

They noted, however, that about half of all patients with relapsed or refractory large B-cell lymphomas will not have durable responses to CAR T-cell therapy directed against CD19, and that new strategies will be needed to improve responses (N Engl J Med. 2017 Dec 10; doi: 10.1056/NEJMe1714680).

In the question and answer session at the end of the briefing, Dr. Neelapu said the preliminary observations of mechanisms of relapse or disease progression in some patients may be related to the loss of the CD19 antigen, which occurs in about one-third of patients who experience relapse, and to high expression of the programmed death ligand-1, which can potentially inhibit CAR-T cell function. A clinical trial is currently underway to evaluate potential strategies for improving response rates to CAR-T therapies, he said.

ZUMA-1 is supported by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program. Dr. Neelapu reported receiving advisory board fees from the company. Myriad coauthors also reported financial relationship with multiple companies.

SOURCE: Neelapu S et al. ASH 2017 Abstract 578.

Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

⁹⁰Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.
 

[email protected]

Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

⁹⁰Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.
 

[email protected]

Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

⁹⁰Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.
 

[email protected]

Epidermotropic marginal zone lymphoma (MZL), a rare cutaneous B-cell lymphoma identified in only eight patients to date, appears to be responsive to rituximab, according to authors of a case report.

A 69-year-old man who presented with a generalized papulosquamous eruption that was eventually diagnosed as epidermotropic MZL achieved a near total remission within 3 months of receiving four total weekly rituximab infusions, reported Cynthia M. Magro, MD, from Cornell University, New York, and her colleagues from the University of Arizona, Tucson (JAAD Case Rep. 2017 Sep 23;3[6]:474-6).

“Epidermotropic MZL represents a distinctive nosologic B-cell lymphoma that should be considered a diagnostic possibility in older men who present with an unexplained papulosquamous eruption resembling pityriasis rosea,” the researchers wrote.

“Epidermotropism refers to a state of abnormal colonization of the epidermis by leukocytes, which often reflects a clonal T-cell or monocyte dyscrasia. Epidermotropism is a distinctive pattern of passive migration into epithelial structures that is not otherwise attributable to the normal function of innate and adaptive immunity,” the researchers explained.

They described the case of the aforementioned patient, who presented with asymptomatic indurated, red-to-brown papules and plaques on his chest, abdomen, back, and buttocks, which gave the clinical impression of pityriasis rosea or a similarly appearing drug reaction.

Histopathologic examination of two biopsied lesions “demonstrated a dense superficial lymphocytic infiltrate that expanded and effaced the papillary and superficial reticular dermis.”

After epidermotropic MZL was diagnosed, the patient was evaluated for systemic disease with a bone marrow biopsy, which revealed a low-grade B-cell lymphoproliferative disorder, and with a PET scan showing lymphomatous infiltration of the spleen. The patient was treated with four weekly infusions of rituximab 375 mg/m².

“Within 3 months, he experienced marked regression of his cutaneous disease. Repeat radiographic imaging found an interval decrease in the size of his spleen, signifying an objective response. Since achieving near total clinical remission, the patient remains under the close observation of medical oncology services,” the researchers wrote.

The investigators noted that if histopathology is the only method used to diagnosis the condition, epidermotropic MZL could be mistaken for a T-cell lymphoproliferative disorder, such as mycosis fungoides, because of the similar architecture at low resolution.

“In these settings, immunohistochemical staining for B-cell markers represents an indispensable diagnostic test,” they wrote.

The researchers reported having no conflicts of interest.

[email protected]

Epidermotropic marginal zone lymphoma (MZL), a rare cutaneous B-cell lymphoma identified in only eight patients to date, appears to be responsive to rituximab, according to authors of a case report.

A 69-year-old man who presented with a generalized papulosquamous eruption that was eventually diagnosed as epidermotropic MZL achieved a near total remission within 3 months of receiving four total weekly rituximab infusions, reported Cynthia M. Magro, MD, from Cornell University, New York, and her colleagues from the University of Arizona, Tucson (JAAD Case Rep. 2017 Sep 23;3[6]:474-6).

“Epidermotropic MZL represents a distinctive nosologic B-cell lymphoma that should be considered a diagnostic possibility in older men who present with an unexplained papulosquamous eruption resembling pityriasis rosea,” the researchers wrote.

“Epidermotropism refers to a state of abnormal colonization of the epidermis by leukocytes, which often reflects a clonal T-cell or monocyte dyscrasia. Epidermotropism is a distinctive pattern of passive migration into epithelial structures that is not otherwise attributable to the normal function of innate and adaptive immunity,” the researchers explained.

They described the case of the aforementioned patient, who presented with asymptomatic indurated, red-to-brown papules and plaques on his chest, abdomen, back, and buttocks, which gave the clinical impression of pityriasis rosea or a similarly appearing drug reaction.

Histopathologic examination of two biopsied lesions “demonstrated a dense superficial lymphocytic infiltrate that expanded and effaced the papillary and superficial reticular dermis.”

After epidermotropic MZL was diagnosed, the patient was evaluated for systemic disease with a bone marrow biopsy, which revealed a low-grade B-cell lymphoproliferative disorder, and with a PET scan showing lymphomatous infiltration of the spleen. The patient was treated with four weekly infusions of rituximab 375 mg/m².

“Within 3 months, he experienced marked regression of his cutaneous disease. Repeat radiographic imaging found an interval decrease in the size of his spleen, signifying an objective response. Since achieving near total clinical remission, the patient remains under the close observation of medical oncology services,” the researchers wrote.

The investigators noted that if histopathology is the only method used to diagnosis the condition, epidermotropic MZL could be mistaken for a T-cell lymphoproliferative disorder, such as mycosis fungoides, because of the similar architecture at low resolution.

“In these settings, immunohistochemical staining for B-cell markers represents an indispensable diagnostic test,” they wrote.

The researchers reported having no conflicts of interest.

[email protected]

Epidermotropic marginal zone lymphoma (MZL), a rare cutaneous B-cell lymphoma identified in only eight patients to date, appears to be responsive to rituximab, according to authors of a case report.

A 69-year-old man who presented with a generalized papulosquamous eruption that was eventually diagnosed as epidermotropic MZL achieved a near total remission within 3 months of receiving four total weekly rituximab infusions, reported Cynthia M. Magro, MD, from Cornell University, New York, and her colleagues from the University of Arizona, Tucson (JAAD Case Rep. 2017 Sep 23;3[6]:474-6).

“Epidermotropic MZL represents a distinctive nosologic B-cell lymphoma that should be considered a diagnostic possibility in older men who present with an unexplained papulosquamous eruption resembling pityriasis rosea,” the researchers wrote.

“Epidermotropism refers to a state of abnormal colonization of the epidermis by leukocytes, which often reflects a clonal T-cell or monocyte dyscrasia. Epidermotropism is a distinctive pattern of passive migration into epithelial structures that is not otherwise attributable to the normal function of innate and adaptive immunity,” the researchers explained.

They described the case of the aforementioned patient, who presented with asymptomatic indurated, red-to-brown papules and plaques on his chest, abdomen, back, and buttocks, which gave the clinical impression of pityriasis rosea or a similarly appearing drug reaction.

Histopathologic examination of two biopsied lesions “demonstrated a dense superficial lymphocytic infiltrate that expanded and effaced the papillary and superficial reticular dermis.”

After epidermotropic MZL was diagnosed, the patient was evaluated for systemic disease with a bone marrow biopsy, which revealed a low-grade B-cell lymphoproliferative disorder, and with a PET scan showing lymphomatous infiltration of the spleen. The patient was treated with four weekly infusions of rituximab 375 mg/m².

“Within 3 months, he experienced marked regression of his cutaneous disease. Repeat radiographic imaging found an interval decrease in the size of his spleen, signifying an objective response. Since achieving near total clinical remission, the patient remains under the close observation of medical oncology services,” the researchers wrote.

The investigators noted that if histopathology is the only method used to diagnosis the condition, epidermotropic MZL could be mistaken for a T-cell lymphoproliferative disorder, such as mycosis fungoides, because of the similar architecture at low resolution.

“In these settings, immunohistochemical staining for B-cell markers represents an indispensable diagnostic test,” they wrote.

The researchers reported having no conflicts of interest.

[email protected]

For patients with advanced or recurrent marginal zone lymphomas (MZL) typically treated with radiotherapy, antibiotics, single-agent therapy, or observation, upfront chemotherapy was associated with high rates of both failure-free and overall survival at 10 years.

A retrospective analysis of data on 44 patients with either extranodal MZL (MALT), splenic MZL (SMZL), or nodal MZL (NMZL) treated with either the standard of care (for early-stage MALT) or with chemotherapy plus rituximab (for patients with advanced MALT, SMZL, or NMZL) showed a projected 10-year failure-free survival rate of 80%, and an overall survival rate of 100%, reported José L. Ortega, MD, of the University of Puerto Rico in San Juan, and his colleagues (Clin Lymphoma Myeloma Leuk. 2017 Sep 23. pii: S2152-2650[17]30632-8. doi: 10.1016/j.clml.2017.09.014).

“Although the watch and wait modality is still the most-used strategy for patients with advanced MZLs, with chemotherapy traditionally reserved for relapsed or advanced symptomatic disease, our data suggest that upfront chemotherapy is very effective for patients with advanced MALT, SMZL, and NMZL. However, it was not possible to definitely exclude that a less-aggressive approach such as single-agent rituximab could yield similar results,” the investigators wrote.

The standard of care for patients with localized MALT has traditionally been either antibiotic therapy for gastric MALT, or radiotherapy when antibiotics are not feasible. There is no standard of care, however, for either SMZL or NMZL, which are typically managed with either observation or single-agent rituximab, the investigators stated.

To see whether upfront chemotherapy with either FND-R (fludarabine, mitoxantrone, dexamethasone, and rituximab) or CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) could improve outcomes in patients with advanced or recurrent MZLs, the investigators conducted a retrospective study of outcomes for 44 patients treated at their institution.

Group 1 comprised 22 patients with early-stage MALT treated with either radiotherapy or antibiotics, with or without surgery. Group 2 comprised 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Patients in this group underwent upfront chemotherapy with either FND-R (14 patients) or CHOP-R (8 patients). In addition, 16 patients in group 2 received maintenance rituximab.

All patients in each group had complete remissions. Two patients in group 1 had relapses (one at 70 months and one at 75 months) of stage I MALT that had previously been treated with radiotherapy. Both patients underwent salvage FND-R, and remained disease free at 27 and 39 months after relapse. There were no relapses in group 2.

The investigators deemed long-term toxicities to be “acceptable,” with most adverse effects in group 2 being hematologic in origin, including grade 3 or 4 neutropenia in 70%, thrombocytopenia in 22%, and anemia in 17%. Nonhematologic adverse events were mostly grade 1 or 2. There were no second malignancies reported at the most recent follow-up.

The investigators noted that the high complete remission rate and durable remissions with FND-R suggest that it has excellent activity against MZL, and that the long failure-free survival suggests the possibility of cure. They acknowledged, however, that their impressions were based on retrospective data and a small sample size, and that larger clinical trials are needed to confirm their results.

The investigators reported having no conflicts of interest.

[email protected]

For patients with advanced or recurrent marginal zone lymphomas (MZL) typically treated with radiotherapy, antibiotics, single-agent therapy, or observation, upfront chemotherapy was associated with high rates of both failure-free and overall survival at 10 years.

A retrospective analysis of data on 44 patients with either extranodal MZL (MALT), splenic MZL (SMZL), or nodal MZL (NMZL) treated with either the standard of care (for early-stage MALT) or with chemotherapy plus rituximab (for patients with advanced MALT, SMZL, or NMZL) showed a projected 10-year failure-free survival rate of 80%, and an overall survival rate of 100%, reported José L. Ortega, MD, of the University of Puerto Rico in San Juan, and his colleagues (Clin Lymphoma Myeloma Leuk. 2017 Sep 23. pii: S2152-2650[17]30632-8. doi: 10.1016/j.clml.2017.09.014).

“Although the watch and wait modality is still the most-used strategy for patients with advanced MZLs, with chemotherapy traditionally reserved for relapsed or advanced symptomatic disease, our data suggest that upfront chemotherapy is very effective for patients with advanced MALT, SMZL, and NMZL. However, it was not possible to definitely exclude that a less-aggressive approach such as single-agent rituximab could yield similar results,” the investigators wrote.

The standard of care for patients with localized MALT has traditionally been either antibiotic therapy for gastric MALT, or radiotherapy when antibiotics are not feasible. There is no standard of care, however, for either SMZL or NMZL, which are typically managed with either observation or single-agent rituximab, the investigators stated.

To see whether upfront chemotherapy with either FND-R (fludarabine, mitoxantrone, dexamethasone, and rituximab) or CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) could improve outcomes in patients with advanced or recurrent MZLs, the investigators conducted a retrospective study of outcomes for 44 patients treated at their institution.

Group 1 comprised 22 patients with early-stage MALT treated with either radiotherapy or antibiotics, with or without surgery. Group 2 comprised 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Patients in this group underwent upfront chemotherapy with either FND-R (14 patients) or CHOP-R (8 patients). In addition, 16 patients in group 2 received maintenance rituximab.

All patients in each group had complete remissions. Two patients in group 1 had relapses (one at 70 months and one at 75 months) of stage I MALT that had previously been treated with radiotherapy. Both patients underwent salvage FND-R, and remained disease free at 27 and 39 months after relapse. There were no relapses in group 2.

The investigators deemed long-term toxicities to be “acceptable,” with most adverse effects in group 2 being hematologic in origin, including grade 3 or 4 neutropenia in 70%, thrombocytopenia in 22%, and anemia in 17%. Nonhematologic adverse events were mostly grade 1 or 2. There were no second malignancies reported at the most recent follow-up.

The investigators noted that the high complete remission rate and durable remissions with FND-R suggest that it has excellent activity against MZL, and that the long failure-free survival suggests the possibility of cure. They acknowledged, however, that their impressions were based on retrospective data and a small sample size, and that larger clinical trials are needed to confirm their results.

The investigators reported having no conflicts of interest.

[email protected]

For patients with advanced or recurrent marginal zone lymphomas (MZL) typically treated with radiotherapy, antibiotics, single-agent therapy, or observation, upfront chemotherapy was associated with high rates of both failure-free and overall survival at 10 years.

A retrospective analysis of data on 44 patients with either extranodal MZL (MALT), splenic MZL (SMZL), or nodal MZL (NMZL) treated with either the standard of care (for early-stage MALT) or with chemotherapy plus rituximab (for patients with advanced MALT, SMZL, or NMZL) showed a projected 10-year failure-free survival rate of 80%, and an overall survival rate of 100%, reported José L. Ortega, MD, of the University of Puerto Rico in San Juan, and his colleagues (Clin Lymphoma Myeloma Leuk. 2017 Sep 23. pii: S2152-2650[17]30632-8. doi: 10.1016/j.clml.2017.09.014).

“Although the watch and wait modality is still the most-used strategy for patients with advanced MZLs, with chemotherapy traditionally reserved for relapsed or advanced symptomatic disease, our data suggest that upfront chemotherapy is very effective for patients with advanced MALT, SMZL, and NMZL. However, it was not possible to definitely exclude that a less-aggressive approach such as single-agent rituximab could yield similar results,” the investigators wrote.

The standard of care for patients with localized MALT has traditionally been either antibiotic therapy for gastric MALT, or radiotherapy when antibiotics are not feasible. There is no standard of care, however, for either SMZL or NMZL, which are typically managed with either observation or single-agent rituximab, the investigators stated.

To see whether upfront chemotherapy with either FND-R (fludarabine, mitoxantrone, dexamethasone, and rituximab) or CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) could improve outcomes in patients with advanced or recurrent MZLs, the investigators conducted a retrospective study of outcomes for 44 patients treated at their institution.

Group 1 comprised 22 patients with early-stage MALT treated with either radiotherapy or antibiotics, with or without surgery. Group 2 comprised 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Patients in this group underwent upfront chemotherapy with either FND-R (14 patients) or CHOP-R (8 patients). In addition, 16 patients in group 2 received maintenance rituximab.

All patients in each group had complete remissions. Two patients in group 1 had relapses (one at 70 months and one at 75 months) of stage I MALT that had previously been treated with radiotherapy. Both patients underwent salvage FND-R, and remained disease free at 27 and 39 months after relapse. There were no relapses in group 2.

The investigators deemed long-term toxicities to be “acceptable,” with most adverse effects in group 2 being hematologic in origin, including grade 3 or 4 neutropenia in 70%, thrombocytopenia in 22%, and anemia in 17%. Nonhematologic adverse events were mostly grade 1 or 2. There were no second malignancies reported at the most recent follow-up.

The investigators noted that the high complete remission rate and durable remissions with FND-R suggest that it has excellent activity against MZL, and that the long failure-free survival suggests the possibility of cure. They acknowledged, however, that their impressions were based on retrospective data and a small sample size, and that larger clinical trials are needed to confirm their results.

The investigators reported having no conflicts of interest.

[email protected]

Findings from several studies on marginal zone lymphoma (MZL) will be presented during oral and poster sessions at the annual meeting of the American Society of Hematology, with a focus on evaluating combination treatment approaches.

Some of the MZL treatment–related studies include the assessment of chlorambucil plus rituximab in patients with extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue, the combination of bendamustine with rituximab for first-line treatment of splenic MZL, and the safety and progression-free survival associated with lenalidomide and rituximab in previously untreated patients with MZL.

Other studies consider how to approach refractory disease. One study looks at the use of ibrutinib in patients with relapsed/refractory MZL, and researchers will also present findings from a systematic literature review of the efficacy and safety of various treatments among patients with relapsed/refractory MZL.

Abstract 1506: IELSG-38: A Phase II Study of Chlorambucil in Combination with Rituximab Followed by Maintenance Therapy with Subcutaneous Rituximab in Patients with Extranodal Marginal Zone B-Cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT) .

Abstract 4062: Bendamustine in Combination with Rituximab as First-Line Treatment of Splenic Marginal Zone Lymphoma (BRISMA). Results of the IELSG-36 Phase II Study.

Abstract 3026: Ibrutinib Therapy in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Analysis by Prior Rituximab Treatment and Baseline Mutations.

Abstract 4040: Safety and Activity of Lenalidomide and Rituximab in Previously Untreated Marginal Zone Lymphoma: Subgroup Analysis and Long-Term Follow-Up of an Open-Label Phase II Trial.

Abstract 2783: Systematic Literature Review of the Clinical Efficacy and Safety of Treatments in the Relapsed/Refractory Setting for Patients with Follicular Lymphoma or Marginal Zone Lymphoma.

[email protected]

Findings from several studies on marginal zone lymphoma (MZL) will be presented during oral and poster sessions at the annual meeting of the American Society of Hematology, with a focus on evaluating combination treatment approaches.

Some of the MZL treatment–related studies include the assessment of chlorambucil plus rituximab in patients with extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue, the combination of bendamustine with rituximab for first-line treatment of splenic MZL, and the safety and progression-free survival associated with lenalidomide and rituximab in previously untreated patients with MZL.

Other studies consider how to approach refractory disease. One study looks at the use of ibrutinib in patients with relapsed/refractory MZL, and researchers will also present findings from a systematic literature review of the efficacy and safety of various treatments among patients with relapsed/refractory MZL.

Abstract 1506: IELSG-38: A Phase II Study of Chlorambucil in Combination with Rituximab Followed by Maintenance Therapy with Subcutaneous Rituximab in Patients with Extranodal Marginal Zone B-Cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT) .

Abstract 4062: Bendamustine in Combination with Rituximab as First-Line Treatment of Splenic Marginal Zone Lymphoma (BRISMA). Results of the IELSG-36 Phase II Study.

Abstract 3026: Ibrutinib Therapy in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Analysis by Prior Rituximab Treatment and Baseline Mutations.

Abstract 4040: Safety and Activity of Lenalidomide and Rituximab in Previously Untreated Marginal Zone Lymphoma: Subgroup Analysis and Long-Term Follow-Up of an Open-Label Phase II Trial.

Abstract 2783: Systematic Literature Review of the Clinical Efficacy and Safety of Treatments in the Relapsed/Refractory Setting for Patients with Follicular Lymphoma or Marginal Zone Lymphoma.

[email protected]

Findings from several studies on marginal zone lymphoma (MZL) will be presented during oral and poster sessions at the annual meeting of the American Society of Hematology, with a focus on evaluating combination treatment approaches.

Some of the MZL treatment–related studies include the assessment of chlorambucil plus rituximab in patients with extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue, the combination of bendamustine with rituximab for first-line treatment of splenic MZL, and the safety and progression-free survival associated with lenalidomide and rituximab in previously untreated patients with MZL.

Other studies consider how to approach refractory disease. One study looks at the use of ibrutinib in patients with relapsed/refractory MZL, and researchers will also present findings from a systematic literature review of the efficacy and safety of various treatments among patients with relapsed/refractory MZL.

Abstract 1506: IELSG-38: A Phase II Study of Chlorambucil in Combination with Rituximab Followed by Maintenance Therapy with Subcutaneous Rituximab in Patients with Extranodal Marginal Zone B-Cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT) .

Abstract 4062: Bendamustine in Combination with Rituximab as First-Line Treatment of Splenic Marginal Zone Lymphoma (BRISMA). Results of the IELSG-36 Phase II Study.

Abstract 3026: Ibrutinib Therapy in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Analysis by Prior Rituximab Treatment and Baseline Mutations.

Abstract 4040: Safety and Activity of Lenalidomide and Rituximab in Previously Untreated Marginal Zone Lymphoma: Subgroup Analysis and Long-Term Follow-Up of an Open-Label Phase II Trial.

Abstract 2783: Systematic Literature Review of the Clinical Efficacy and Safety of Treatments in the Relapsed/Refractory Setting for Patients with Follicular Lymphoma or Marginal Zone Lymphoma.

[email protected]