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Addition of bortezomib to R-CHOP improves survival in DLBCL molecular subgroups

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Key clinical point: The addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) confers a survival advantage over R-CHOP in patients with activated B-cell (ABC)- and molecular high grade (MHG)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Bortezomib-R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P  =  .041) and MHG (aHR 0.46; P  =  .011) groups, and overall survival (OS) in the ABC group (aHR 0.58; P  =  .032). The germinal center B-cell (GCB) group showed no significant difference in PFS or OS.

Study details: This updated retrospective analysis of the phase 3 REMoDL-B study included 801 adult patients with DLBCL (ABC, MHG, or GCB subtype) who were randomly assigned to receive 2-6 cycles of R-CHOP (n = 407) or bortezomib-R-CHOP (n = 394) after one cycle of R-CHOP.

Disclosures: This study was supported by a grant from Janssen-Cilag and Cancer Research UK. Some authors reported ties with various organizations, including Janssen.

Source: Davies AJ et al. Differential efficacy from the addition of bortezomib to r-chop in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. 2023 (Mar 27). Doi: 10.1200/JCO.23.00033

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Key clinical point: The addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) confers a survival advantage over R-CHOP in patients with activated B-cell (ABC)- and molecular high grade (MHG)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Bortezomib-R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P  =  .041) and MHG (aHR 0.46; P  =  .011) groups, and overall survival (OS) in the ABC group (aHR 0.58; P  =  .032). The germinal center B-cell (GCB) group showed no significant difference in PFS or OS.

Study details: This updated retrospective analysis of the phase 3 REMoDL-B study included 801 adult patients with DLBCL (ABC, MHG, or GCB subtype) who were randomly assigned to receive 2-6 cycles of R-CHOP (n = 407) or bortezomib-R-CHOP (n = 394) after one cycle of R-CHOP.

Disclosures: This study was supported by a grant from Janssen-Cilag and Cancer Research UK. Some authors reported ties with various organizations, including Janssen.

Source: Davies AJ et al. Differential efficacy from the addition of bortezomib to r-chop in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. 2023 (Mar 27). Doi: 10.1200/JCO.23.00033

Key clinical point: The addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) confers a survival advantage over R-CHOP in patients with activated B-cell (ABC)- and molecular high grade (MHG)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Bortezomib-R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P  =  .041) and MHG (aHR 0.46; P  =  .011) groups, and overall survival (OS) in the ABC group (aHR 0.58; P  =  .032). The germinal center B-cell (GCB) group showed no significant difference in PFS or OS.

Study details: This updated retrospective analysis of the phase 3 REMoDL-B study included 801 adult patients with DLBCL (ABC, MHG, or GCB subtype) who were randomly assigned to receive 2-6 cycles of R-CHOP (n = 407) or bortezomib-R-CHOP (n = 394) after one cycle of R-CHOP.

Disclosures: This study was supported by a grant from Janssen-Cilag and Cancer Research UK. Some authors reported ties with various organizations, including Janssen.

Source: Davies AJ et al. Differential efficacy from the addition of bortezomib to r-chop in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. 2023 (Mar 27). Doi: 10.1200/JCO.23.00033

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Ibrutinib offers better efficacy and tolerability over idelalisib+rituximab in relapsed/refractory CLL

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Thu, 05/18/2023 - 14:30

Key clinical point: Compared with idelalisib+rituximab (R-idela), ibrutinib significantly prolonged survival and was associated with lower treatment discontinuation rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) in routine practice.

Major finding: The ibrutinib vs R-idela group had significantly longer median progression-free survival (40.5 vs 22.0 months; hazard ratio [HR] 0.55; P < .001) and overall survival (54.4 vs 37.7 months; HR 0.73; P  =  .040) and lower rates of treatment discontinuation due to toxicity (22.5% vs 39.8%) and CLL progression (11.1% vs 27.5%).

Study details: This real-world retrospective study included 415 patients with relapsed or refractory CLL from the Chronic Lymphocytic Leukemia Patients Registry who received R-idela (n = 171) or ibrutinib (n = 244).

Disclosures: This study was funded by grants from the Ministry of Health, Czech Republic, and Programme Cooperation, Research Area ONCO. Some authors reported ties with various organizations.

Source: Spacek M et al for the Czech CLL Study Group. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR). Br J Haematol. 2023 (Mar 27). Doi: 10.1111/bjh.18736

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Key clinical point: Compared with idelalisib+rituximab (R-idela), ibrutinib significantly prolonged survival and was associated with lower treatment discontinuation rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) in routine practice.

Major finding: The ibrutinib vs R-idela group had significantly longer median progression-free survival (40.5 vs 22.0 months; hazard ratio [HR] 0.55; P < .001) and overall survival (54.4 vs 37.7 months; HR 0.73; P  =  .040) and lower rates of treatment discontinuation due to toxicity (22.5% vs 39.8%) and CLL progression (11.1% vs 27.5%).

Study details: This real-world retrospective study included 415 patients with relapsed or refractory CLL from the Chronic Lymphocytic Leukemia Patients Registry who received R-idela (n = 171) or ibrutinib (n = 244).

Disclosures: This study was funded by grants from the Ministry of Health, Czech Republic, and Programme Cooperation, Research Area ONCO. Some authors reported ties with various organizations.

Source: Spacek M et al for the Czech CLL Study Group. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR). Br J Haematol. 2023 (Mar 27). Doi: 10.1111/bjh.18736

Key clinical point: Compared with idelalisib+rituximab (R-idela), ibrutinib significantly prolonged survival and was associated with lower treatment discontinuation rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) in routine practice.

Major finding: The ibrutinib vs R-idela group had significantly longer median progression-free survival (40.5 vs 22.0 months; hazard ratio [HR] 0.55; P < .001) and overall survival (54.4 vs 37.7 months; HR 0.73; P  =  .040) and lower rates of treatment discontinuation due to toxicity (22.5% vs 39.8%) and CLL progression (11.1% vs 27.5%).

Study details: This real-world retrospective study included 415 patients with relapsed or refractory CLL from the Chronic Lymphocytic Leukemia Patients Registry who received R-idela (n = 171) or ibrutinib (n = 244).

Disclosures: This study was funded by grants from the Ministry of Health, Czech Republic, and Programme Cooperation, Research Area ONCO. Some authors reported ties with various organizations.

Source: Spacek M et al for the Czech CLL Study Group. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR). Br J Haematol. 2023 (Mar 27). Doi: 10.1111/bjh.18736

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Similar outcomes of CAR-T cell therapy for nodal and extra nodal DLBCL

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Thu, 05/18/2023 - 14:27

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

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Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

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Dose-adjusted EPOCH and rituximab beneficial for selected older patients with high-risk DLBCL

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Thu, 05/18/2023 - 14:25

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

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Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

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Axi-cel a promising second-line treatment option for older patients with relapsed or refractory LBCL

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Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

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Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

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Lenalidomide+rituximab+venetoclax a potential therapy option for untreated MCL

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Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

 

 

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Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

 

 

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

 

 

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Higher rates of hospitalization, blood disorders, and infections among patients with MCL

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Thu, 05/18/2023 - 13:56

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

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Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

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Ibrutinib+BR a promising treatment option for newly diagnosed MCL ineligible for intensive therapy

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Thu, 05/18/2023 - 13:46

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

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Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

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Real-world data support the continued use of second-line targeted therapies in CLL

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Thu, 05/18/2023 - 13:42

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

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Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

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A 50-year-old White male presented with a 4- to 5-year history of progressively growing violaceous lesions on his left lower extremity

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Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a specific categorization of cutaneous B-cell lymphoma (CBCL) demonstrating a predominance of immunoblasts and centroblasts with scarce T-cells, classically presenting as rapidly progressive, plum-colored lesions on the lower extremities.1,2 CBCLs, with PCDLBCL-LT accounting for 4%, make up the minority of cutaneous lymphomas in the Western world.1-3 The leg type variant, typically demonstrating a female predominance and median age of onset in the 70s, is clinically aggressive and associated with a poorer prognosis, increased recurrence rate, and 40%-60% 5-year survival rate.1-5

Histologically, this variant demonstrates a diffuse sheet-like growth of enlarged atypical B-cells distinctively separated from the epidermis by a prominent grenz zone. Classic PCDLBCL-LT immunophenotype includes B-cell markers CD20 and IgM; triple expressor phenotype indicating c-MYC, BCL-2, and BCL-6 positivity; as well as CD10 negativity, lack of BCL-2 rearrangement, and presence of a positive MYD-88 molecular result.

Marlee Hill, University of Oklahoma

Other characteristic histopathological findings include positivity for post-germinal markers IRF4/MUM-1 and FOXP-1, positivity for additional B-cell markers, including CD79 and PAX5, and negativity of t(14;18) (q32;21).1,3-5

This case is of significant interest as it falls within the approximately 10% of PCDLBCL-LT cases demonstrating weak to negative MUM-1 staining, in addition to its presentation in a younger male individual.

Marlee Hill, University of Oklahoma

While MUM-1 positivity is common in this subtype, its presence, or lack thereof, should not be looked at in isolation when evaluating diagnostic criteria, nor has it been shown to have a statistically significant effect on survival rate – in contrast to factors like lesion location on the leg versus non-leg lesions, multiple lesions at diagnosis, and dissemination to other sites.2,6

PCDLBCL-LT can uncommonly present in non-leg locations and only 10% depict associated B-symptoms, such as fatigue, night sweats, weight loss, or lymphadenopathy.2,6 First-line treatment is with the R-CHOP chemotherapy regimen – consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone – although radiotherapy is sometimes considered in patients with a single small lesion.1,2

Dr. Donna Bilu Martin

Because of possible cutaneous involvement beyond the legs, common lack of systemic symptoms, and variable immunophenotypes, this case of MUM-1 negative PCDLBCL-LT highlights the importance of a clinicopathological approach to differentiate the subtypes of CBCLs, allowing for proper and individualized stratification of risk, prognosis, and treatment.
 

This case was submitted and written by Marlee Hill, BS, Michael Franzetti, MD, Jeffrey McBride, MD, and Allison Hood, MD, of the University of Oklahoma, Oklahoma City. They also provided the photos. Donna Bilu Martin, MD, edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Willemze R et al. Blood. 2019;133(16):1703-14.

2. Willemze R et al. Blood. 2005;105(10):3768-85.

3. Sukswai N et al. Pathology. 2020;52(1):53-67.

4. Hristov AC. Arch Pathol Lab Med. 2012;136(8):876-81.

5. Sokol L et al. Cancer Control. 2012;19(3):236-44.

6. Grange F et al. Arch Dermatol. 2007;143(9):1144-50.

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Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a specific categorization of cutaneous B-cell lymphoma (CBCL) demonstrating a predominance of immunoblasts and centroblasts with scarce T-cells, classically presenting as rapidly progressive, plum-colored lesions on the lower extremities.1,2 CBCLs, with PCDLBCL-LT accounting for 4%, make up the minority of cutaneous lymphomas in the Western world.1-3 The leg type variant, typically demonstrating a female predominance and median age of onset in the 70s, is clinically aggressive and associated with a poorer prognosis, increased recurrence rate, and 40%-60% 5-year survival rate.1-5

Histologically, this variant demonstrates a diffuse sheet-like growth of enlarged atypical B-cells distinctively separated from the epidermis by a prominent grenz zone. Classic PCDLBCL-LT immunophenotype includes B-cell markers CD20 and IgM; triple expressor phenotype indicating c-MYC, BCL-2, and BCL-6 positivity; as well as CD10 negativity, lack of BCL-2 rearrangement, and presence of a positive MYD-88 molecular result.

Marlee Hill, University of Oklahoma

Other characteristic histopathological findings include positivity for post-germinal markers IRF4/MUM-1 and FOXP-1, positivity for additional B-cell markers, including CD79 and PAX5, and negativity of t(14;18) (q32;21).1,3-5

This case is of significant interest as it falls within the approximately 10% of PCDLBCL-LT cases demonstrating weak to negative MUM-1 staining, in addition to its presentation in a younger male individual.

Marlee Hill, University of Oklahoma

While MUM-1 positivity is common in this subtype, its presence, or lack thereof, should not be looked at in isolation when evaluating diagnostic criteria, nor has it been shown to have a statistically significant effect on survival rate – in contrast to factors like lesion location on the leg versus non-leg lesions, multiple lesions at diagnosis, and dissemination to other sites.2,6

PCDLBCL-LT can uncommonly present in non-leg locations and only 10% depict associated B-symptoms, such as fatigue, night sweats, weight loss, or lymphadenopathy.2,6 First-line treatment is with the R-CHOP chemotherapy regimen – consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone – although radiotherapy is sometimes considered in patients with a single small lesion.1,2

Dr. Donna Bilu Martin

Because of possible cutaneous involvement beyond the legs, common lack of systemic symptoms, and variable immunophenotypes, this case of MUM-1 negative PCDLBCL-LT highlights the importance of a clinicopathological approach to differentiate the subtypes of CBCLs, allowing for proper and individualized stratification of risk, prognosis, and treatment.
 

This case was submitted and written by Marlee Hill, BS, Michael Franzetti, MD, Jeffrey McBride, MD, and Allison Hood, MD, of the University of Oklahoma, Oklahoma City. They also provided the photos. Donna Bilu Martin, MD, edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Willemze R et al. Blood. 2019;133(16):1703-14.

2. Willemze R et al. Blood. 2005;105(10):3768-85.

3. Sukswai N et al. Pathology. 2020;52(1):53-67.

4. Hristov AC. Arch Pathol Lab Med. 2012;136(8):876-81.

5. Sokol L et al. Cancer Control. 2012;19(3):236-44.

6. Grange F et al. Arch Dermatol. 2007;143(9):1144-50.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a specific categorization of cutaneous B-cell lymphoma (CBCL) demonstrating a predominance of immunoblasts and centroblasts with scarce T-cells, classically presenting as rapidly progressive, plum-colored lesions on the lower extremities.1,2 CBCLs, with PCDLBCL-LT accounting for 4%, make up the minority of cutaneous lymphomas in the Western world.1-3 The leg type variant, typically demonstrating a female predominance and median age of onset in the 70s, is clinically aggressive and associated with a poorer prognosis, increased recurrence rate, and 40%-60% 5-year survival rate.1-5

Histologically, this variant demonstrates a diffuse sheet-like growth of enlarged atypical B-cells distinctively separated from the epidermis by a prominent grenz zone. Classic PCDLBCL-LT immunophenotype includes B-cell markers CD20 and IgM; triple expressor phenotype indicating c-MYC, BCL-2, and BCL-6 positivity; as well as CD10 negativity, lack of BCL-2 rearrangement, and presence of a positive MYD-88 molecular result.

Marlee Hill, University of Oklahoma

Other characteristic histopathological findings include positivity for post-germinal markers IRF4/MUM-1 and FOXP-1, positivity for additional B-cell markers, including CD79 and PAX5, and negativity of t(14;18) (q32;21).1,3-5

This case is of significant interest as it falls within the approximately 10% of PCDLBCL-LT cases demonstrating weak to negative MUM-1 staining, in addition to its presentation in a younger male individual.

Marlee Hill, University of Oklahoma

While MUM-1 positivity is common in this subtype, its presence, or lack thereof, should not be looked at in isolation when evaluating diagnostic criteria, nor has it been shown to have a statistically significant effect on survival rate – in contrast to factors like lesion location on the leg versus non-leg lesions, multiple lesions at diagnosis, and dissemination to other sites.2,6

PCDLBCL-LT can uncommonly present in non-leg locations and only 10% depict associated B-symptoms, such as fatigue, night sweats, weight loss, or lymphadenopathy.2,6 First-line treatment is with the R-CHOP chemotherapy regimen – consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone – although radiotherapy is sometimes considered in patients with a single small lesion.1,2

Dr. Donna Bilu Martin

Because of possible cutaneous involvement beyond the legs, common lack of systemic symptoms, and variable immunophenotypes, this case of MUM-1 negative PCDLBCL-LT highlights the importance of a clinicopathological approach to differentiate the subtypes of CBCLs, allowing for proper and individualized stratification of risk, prognosis, and treatment.
 

This case was submitted and written by Marlee Hill, BS, Michael Franzetti, MD, Jeffrey McBride, MD, and Allison Hood, MD, of the University of Oklahoma, Oklahoma City. They also provided the photos. Donna Bilu Martin, MD, edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Willemze R et al. Blood. 2019;133(16):1703-14.

2. Willemze R et al. Blood. 2005;105(10):3768-85.

3. Sukswai N et al. Pathology. 2020;52(1):53-67.

4. Hristov AC. Arch Pathol Lab Med. 2012;136(8):876-81.

5. Sokol L et al. Cancer Control. 2012;19(3):236-44.

6. Grange F et al. Arch Dermatol. 2007;143(9):1144-50.

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A 50-year-old White male presented for evaluation of a 4- to 5-year history of progressively growing violaceous lesions on his left lower extremity, unresponsive to over-the-counter treatments.

He denied fever, chills, night sweats, easy bruising, or skin cancer history but noted a 35-pound weight loss over the past 2 years. Physical exam demonstrated multiple clustered erythematous and violaceous patches and nodules on the medial, anterior, and lateral aspects of the left lower extremity. 

There was no cervical, axillary, or inguinal lymphadenopathy.

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