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Updates in the Treatment of Mantle Cell Lymphoma: A Canadian Expert Framework

Waldenström macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma (NHL) characterized by malignant B cells that produce IgM monoclonal protein. Like other indolent B-cell NHLs, treatment is indicated when patients are symptomatic with lymphadenopathy, splenomegaly or have detrimental cytopenias, but uniquely hyperviscosity and other complications related to gammopathy may present a need for treatment1. Currently in Canada chemoimmunotherapy using bendamustine and rituximab (BR) is the favored therapeutic combination for treatment-naïve patients with WM due to a superior efficacy and toxicity profile compared to rituximab plus CHOP2 and a fixed duration schedule3. The availability of Bruton’s tyrosine kinase inhibitors (BTKi) have transformed the treatment landscape for patients with WM, particularly in the relapsed setting. Ibrutinib, a once-daily BTKi, was approved by Health Canada (HC) for WM in 2016 based on two non-randomized studies showing high response rates in heavily pretreated rituximab-refractory patients with sustained efficacy (86% progression-free survival (PFS) at 18 months) and acceptable tolerability4,5. Ibrutinib forms an irreversible covalent bond to the cysteine residue (C481) at the active binding site of BTK6. Patients with mutated MYD88 (MYD88MUT),
who represent over 90% of patients with WM, have a higher rate of response with ibrutinib than those without (MYD88WT)4,7,8.
Aside from its impressive efficacy, its oral administration offers a major advantage in terms of convenience for patients and lower administrative costs for publicly funded health care systems such as in Canada.

Hereditary Hematologic Malignancies: A Canadian Perspective

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores1. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment2 options versus higher-risk patients (IGVH unmutated3, del 17p or TP534 ) who benefit from continuous therapies5,6. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI)7-10. However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI11. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

Moving beyond Chemotherapy in the Management of Follicular Lymphoma

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores1. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment2 options versus higher-risk patients (IGVH unmutated3, del 17p or TP534 ) who benefit from continuous therapies5,6. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI)7-10. However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI11. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

Evolving Strategies in T-cell Lymphoma

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores1. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment2 options versus higher-risk patients (IGVH unmutated3, del 17p or TP534 ) who benefit from continuous therapies5,6. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI)7-10. However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI11. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

Chronic Myeloid Leukemia: Who Should Get a Treatment-Free Trial and How?

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores1. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment2 options versus higher-risk patients (IGVH unmutated3, del 17p or TP534 ) who benefit from continuous therapies5,6. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI)7-10. However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI11. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

The evolving treatment landscape of higher-risk MDS

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores1. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment2 options versus higher-risk patients (IGVH unmutated3, del 17p or TP534 ) who benefit from continuous therapies5,6. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI)7-10. However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI11. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

Expert clinical framework report: management of adverse events related to novel therapies for relapsed/refractory multiple myeloma (RRMM)

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores1. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment2 options versus higher-risk patients (IGVH unmutated3, del 17p or TP534 ) who benefit from continuous therapies5,6. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI)7-10. However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI11. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

Panel Discussion: Treatment Options for RelapseD/Refractory Diffuse large B cell lymphoma (R/R DLBCL) patients

Waldenström macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma (NHL) characterized by malignant B cells that produce IgM monoclonal protein. Like other indolent B-cell NHLs, treatment is indicated when patients are symptomatic with lymphadenopathy, splenomegaly or have detrimental cytopenias, but uniquely hyperviscosity and other complications related to gammopathy may present a need for treatment1. Currently in Canada chemoimmunotherapy using bendamustine and rituximab (BR) is the favored therapeutic combination for treatment-naïve patients with WM due to a superior efficacy and toxicity profile compared to rituximab plus CHOP2 and a fixed duration schedule3. The availability of Bruton’s tyrosine kinase inhibitors (BTKi) have transformed the treatment landscape for patients with WM, particularly in the relapsed setting. Ibrutinib, a once-daily BTKi, was approved by Health Canada (HC) for WM in 2016 based on two non-randomized studies showing high response rates in heavily pretreated rituximab-refractory patients with sustained efficacy (86% progression-free survival (PFS) at 18 months) and acceptable tolerability4,5. Ibrutinib forms an irreversible covalent bond to the cysteine residue (C481) at the active binding site of BTK6. Patients with mutated MYD88 (MYD88MUT),
who represent over 90% of patients with WM, have a higher rate of response with ibrutinib than those without (MYD88WT)4,7,8.
Aside from its impressive efficacy, its oral administration offers a major advantage in terms of convenience for patients and lower administrative costs for publicly funded health care systems such as in Canada.

Safety and Tolerability of Bruton’s Tyrosine Kinase Inhibitors in the treatment of Waldenström Macroglobulinemia

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Waldenström macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma (NHL) characterized by malignant B cells that produce IgM monoclonal protein. Like other indolent B-cell NHLs, treatment is indicated when patients are symptomatic with lymphadenopathy, splenomegaly or have detrimental cytopenias, but uniquely hyperviscosity and other complications related to gammopathy may present a need for treatment1. Currently in Canada chemoimmunotherapy using bendamustine and rituximab (BR) is the favored therapeutic combination for treatment-naïve patients with WM due to a superior efficacy and toxicity profile compared to rituximab plus CHOP2 and a fixed duration schedule3. The availability of Bruton’s tyrosine kinase inhibitors (BTKi) have transformed the treatment landscape for patients with WM, particularly in the relapsed setting. Ibrutinib, a once-daily BTKi, was approved by Health Canada (HC) for WM in 2016 based on two non-randomized studies showing high response rates in heavily pretreated rituximab-refractory patients with sustained efficacy (86% progression-free survival (PFS) at 18 months) and acceptable tolerability4,5. Ibrutinib forms an irreversible covalent bond to the cysteine residue (C481) at the active binding site of BTK6. Patients with mutated MYD88 (MYD88MUT),
who represent over 90% of patients with WM, have a higher rate of response with ibrutinib than those without (MYD88WT)4,7,8.
Aside from its impressive efficacy, its oral administration offers a major advantage in terms of convenience for patients and lower administrative costs for publicly funded health care systems such as in Canada.