An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered

An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

: Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered

ABCs of ADCs in management of relapsed/refractory diffuse large B-cell lymphoma

In the past 5 years, 3 chimeric antigen receptor (CAR) T-cell therapies, 2 antibody-drug conjugates (ADCs), 1 CD19-directed monoclonal antibody, and 1 exportin-1 inhibitor have been approved by the Food and Drug Administration for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The noncellular therapies received accelerated approval based on the overall response rate in clinical trials that differ in multiple aspects of the patient populations enrolled, including age, performance status, prior lines of therapy, and inclusion of patients with primary refractory DLBCL, transformed lymphoma, or high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6. ADCs approved for DLBCL differ in target antigen, antibody structure, linker, and cytotoxin, which results in a different safety and efficacy profile. Here, we comprehensively review the current knowledge of recently approved and emerging strategies for the management of R/R DLBCL with a focus on ADCs

Expression of germinal center cell markers by extranodal marginal zone lymphomas of MALT type within colonized follicles, a diagnostic pitfall with follicular lymphoma

We reviewed 341 consecutive cases of marginal zone lymphoma (MZL) (47) or follicular lymphoma (FL) (294) of which 7 were difficult to distinguish due to perceived coexpression of BCL6 and BCL2 by tumor cells in follicular foci. This stimulated us to develop dual BCL6/BCL2 immunohistochemistry, allowing us to assess coexpression among individual cells. Dual staining confirmed coexpression in 6 of 7 cases, all extranodal MZL (ENMZL) based on overall features and representing 13% of MZL in this series. These findings confirm that MZL cells have plasticity regarding protein expression within the germinal center (GC) microenvironment, an important diagnostic pitfall. Intriguingly, in all MZL expressing BCL6, non-neoplastic GC B cells within colonized follicles showed diminished or absent CD10 expression but preserved BCL6 and high ki67. This finding suggests plasticity of CD10 expression in non-neoplastic GC B cells in the context of colonization by MZL, possibly related to NF-kB dysregulation

R‐MACLO‐IVAM

We present long-term combined results of two clinical trials implementing R-MACLO-IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM-MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM-MCL2 ClinicalTrials.gov identifier NCT00878254) received rituximab (375 mg/m IV weekly × 4, repeated every 6 months for 3 years). Considering all 44 patients, 41 (93.2%) achieved complete response (CR), two (4.5%) partial response (PR), and one (2.3%) was not evaluated for response. With a median follow up of 7.2 years (range < 1 month to 16 years), the 5-year progression-free survival (PFS) was 55.6% (95% CI: 38.9%-69.4%) and median PFS 7.9 years (95% CI: 3.7-11 years). The 5-year OS was 83.3% (95% CI: 68.1%-91.7%) and median OS was not reached. Patients with blastic variant (n = 6) had a 5-year PFS and OS of 20.8% and 60%, respectively. Myelosuppression was the most common adverse event during immunochemotherapy. Long-term treatment-related mortality was 6.8%. Note, R-MACLO-IVAM followed by maintenance therapy is an effective regimen to induce long-term remission in MCL without need for consolidation with ASCT

Splenic B-Cell Lymphomas with Diffuse Cyclin D1 Protein Expression and Increased Prolymphocytic Cells: A Previously Unrecognized Diagnostic Pitfall

Prolymphocytic transformation is a concept usually applied in the context of chronic lymphocytic leukemia/small lymphocytic lymphoma to describe the presence of a high percentage of prolymphocytes in peripheral blood (usually more than 55%). Prolymphocytic transformation has also been reported in mantle cell lymphoma (MCL) but only rarely in splenic marginal zone lymphoma (SMZL). We present two splenic B-cell lymphomas presenting in the leukemic phase and with increased prolymphocytes, both classified as SMZL with prolymphocytic transformation. One case clinically simulated B-prolymphocytic leukemia (B-PLL). Both lymphomas were very unusual because the tumor cells diffusely and strongly expressed cyclin D1 despite lacking the t(11; 14)(q13; q32) as detected by several approaches including next-generation sequencing, fluorescence in situ hybridization using CCND1 break apart probe and fusion probes for t(11; 14)(q13; q32), and conventional karyotyping. These cases therefore simulated prolymphocytic variants of MCL. The incidence of this phenomenon is unknown, and awareness of this potential alternate protein expression pattern is important in order to avoid diagnostic errors

Unusual Variants of Follicular Lymphoma: Case-based Review

Follicular lymphoma (FL) is one of the most frequently diagnosed lymphomas in the United States and Europe. The definition of and basic approach to diagnosis and grading of FL is essentially unchanged in the recently updated revision of the World Health Organization (WHO) classification. FL is a biologically and histopathologically heterogeneous disease. Although there is an improved understanding of some FL variants and specific subtypes, there are cases whose recognition is particularly challenging, either because they have unusual features or represent examples of new or rare variants. Herein, we share a series of unusual and difficult to recognize FLs with the goal of increasing awareness of the expanding histopathologic variability in FL. Unusual FL discussed here include: FL with Castleman-like changes, FL with plasmacytic differentiation, and immunoglobulin G4-positive plasma cells in the setting of immunoglobulin G4-related disease, FL with marginal zone differentiation and involving mucosa-associated lymphoid tissue sites, diffuse FL variant expressing CD23 with STAT6 mutation, large B-cell lymphoma with IRF4 rearrangement, CD10-negative and MUM1-positive aggressive FL, and Epstein-Barr virus-positive FL