Bendamustine myeloma

Tafasitamab+lenalidomide (LEN), a chemo-free immunotherapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), demonstrated efficacy in autologous stem cell transplant-ineligible patients in the single-arm L-MIND study (NCT02399085). RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared patient outcomes from L-MIND with matched patient cohorts treated with other systemic therapies. Prolonged overall survival (OS) with tafasitamab+LEN was detected compared to a cohort of pooled systemic therapies (PST), bendamustine+rituximab (BR), rituximab+gemcitabine+oxaliplatin, polatuzumab vedotin+BR (pola-BR), and rituximab+LEN (R2)...

CONTEXT: Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have relapsed/refractory (R/R) disease after first-line (1L) treatment with R-CHOP. Treatment options for autologous stem cell transplant (ASCT)-ineligible patients with R/R DLBCL include the chemo-free immunotherapy tafasitamab + lenalidomide, polatuzumab + bendamustine + rituximab, loncastuximab tesirine, selinexor, and CD19 chimeric antigen receptor (CAR) T-cell therapies. Treatment sequencing and identifying the optimal choice for individual patients can be challenging for oncologists...

CONTEXT: Covalent Bruton's Tyrosine Kinase (BTK) inhibitors (BTKi) have transformed the management of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but these treatments are not curative, and the majority of patients will require additional treatment. Covalent BTKi shares pharmacologic liabilities (e.g., low oral bioavailability, short half-life) that collectively may lead to suboptimal BTK target coverage, for example in rapidly proliferating tumors with high BTK protein turnover such as accelerating CLL/SLL, ultimately manifesting as acquired resistance in some patients...

CONTEXT: The Bruton tyrosine kinase (BTK) inhibitor, zanubrutinib, was designed for high BTK specificity and minimal toxicity. SEQUOIA (NCT03336333) is a global, open-label, randomized phase 3 study in treatment-naïve patients with CLL/SLL without del(17p) who were unsuitable for fludarabine/cyclophosphamide/rituximab. DESIGN: Patients were randomized to receive zanubrutinib (160 mg twice daily) or bendamustine (day 1-2: 90 mg/m2 ) and rituximab (cycle 1: 375 mg/m2 ; cycles 2-6: 500 mg/m2 ); stratification factors were age (<65 years vs ≥65 years), Binet Stage, IGHV mutation, and geographic region...

CONTEXT: Covalent Bruton tyrosine kinase (BTK) inhibitors (BTKi) have transformed the management of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but these treatments are not curative. Covalent BTKi share pharmacologic liabilities (e.g., low oral bioavailability, short half-life) that collectively may lead to suboptimal BTK target coverage, ultimately manifesting as acquired resistance in some patients. To address these limitations, pirtobrutinib, a highly selective, non-covalent BTKi that inhibits both wild-type (WT) and C481-mutated BTK with equally low nM potency, was developed...

BACKGROUND: In previous analyses, the MURANO study demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit for fixed-duration venetoclax-rituximab treatment compared with bendamustine-rituximab in relapsed/refractory chronic lymphocytic leukemia patients. Furthermore, the study demonstrated that deep responses with undetectable minimal residual disease (uMRD) were associated with favorable PFS. We designed the "Dedalo" study with the goal of testing MRD from a multidisciplinary point of view (flow cytometry, molecular biology and ultrasound) and of assessing MRD predictive/prognostic value...

PURPOSE: Development of BCL-2-specific inhibitors poses unique challenges in drug design because of BCL-2 homology domain 3 (BH3) shared homology between BCL-2 family members and the shallow surface of their protein-protein interactions. We report herein discovery and extensive preclinical investigation of lisaftoclax (APG-2575). EXPERIMENTAL DESIGN: Computational modeling was used to design "lead" compounds. Biochemical binding, mitochondrial BH3 profiling, and cell-based viability or apoptosis assays were used to determine the selectivity and potency of BCL-2 inhibitor lisaftoclax...

INTRODUCTION: Autologous stem cell transplantation (ASCT) is the standard treatment for younger patients with newly diagnosed multiple myeloma (MM). However, due to restrictive exclusion criteria, more than half of eligible patients are usually excluded from transplant studies. METHODS: This retrospective monocentric analysis included 540 patients with MM who received an ASCT between 1996 and 2019. RESULTS: Up to 2005, induction therapy consisted mainly of conventional chemotherapies, e...

Single-agent high-dose melphalan (Mel) followed by autologous stem cell transplantation (ASCT) remains a standard of care in eligible patients with multiple myeloma (MM), and efforts to improve transplant outcomes by intensifying transplant conditioning have mostly failed. Bendamustine combines both alkylating and antimetabolite properties, can induce responses in MM resistant to other alkylators and represents a promising agent to combine with Mel prior to ASCT. We performed a phase II study to test the safety and efficacy of the high-dose chemotherapy combination of bendamustine, etoposide, cytarabine and melphalan (BeEAM) in newly diagnosed MM patients up to 70 years of age...

The introduction of targeted therapies in chronic lymphocytic leukemia (CLL) has ushered in a new era in which patients achieve better control of their disease, survive longer, and experience fewer toxicities than before. Despite this progress, a subgroup of patients with CLL will develop resistance to both Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 inhibitors. In addition, a subgroup of CLL cases will transform into aggressive lymphoma - called Richter transformation - either before or during targeted therapy...

OBJECTIVES: Bendamustine is a standard treatment for low-grade B-cell lymphomas, and considered safe in clinical trials. Its safety in routine practice might be different. METHODS: We retrospectively analyzed the infection complications in an unselected cohort of patients treated with bendamustine over a nine-year period. Patients were regularly monitored for blood counts and cytomegalovirus (CMV) reactivation by antigen assay and polymerase chain reaction. They received granulocyte colony stimulating factor for neutropenia, and routine anti-pneumocystis and optional anti-fungal prophylaxis...

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m2 day 1, pomalidomide 3 mg days 1-21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30-76) years and 15 (53...

Definite cure remains exceptional in myeloma patients even after high-dose chemotherapy (HDCT) with melphalan (Mel) and autologous stem cell transplantation (ASCT). Thus, improving efficacy of HDCT in MM remains an unresolved issue. This randomized phase II trial compared standard 200 mg/m2 Mel HDCT to experimental HDCT with 200 mg/m2 bendamustine, given both at days -4 and -3, combined with 100 mg/m2 melphalan at days -2 and -1 (BenMel) before ASCT as first-line consolidation in myeloma patients...

DISEASE OVERVIEW: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)." DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis...

Waldenström Macroglobulinemia (WM) is a rare hematologic malignancy characterized by the presence of lymphoplasmacytic lymphoma cells involving the bone marrow and production of a monoclonal IgM paraprotein. Recurrent somatic mutations in MYD88L265P and CXCR4 have been reported in 90% to 95% and 30% to 40% of patients with WM, respectively. Standard treatment regimens combine the anti-CD20 antibody rituximab with alkylating agents (eg, bendamustine, cyclophosphamide), nucleoside analogs (eg, fludarabine, cladribine), or proteasome inhibitors (eg, bortezomib, carfilzomib, and ixazomib)...

Multiple myeloma (MM) is an incurable disease and patients become refractory to the treatment in the course of the disease. Bendamustine-based regimens containing steroids and other agents are among the therapeutic options offered to MM patients. Here, we investigated the safety and the efficacy of bendamustine used in patients with refractory/relapsed MM (RRMM). The patients were treated with bendamustine and steroids ( n = 52) or bendamustine, steroids and immunomodulatory agents or proteasome inhibitors ( n = 53)...

BACKGROUND: Patients with relapsed or refractory classical Hodgkin lymphoma (R/R cHL) have limited opportunities for curative therapy. High-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) produces cure rates of 50% to 60%. Patients relapsing after, or ineligible for HDT-ASCT have limited therapeutic options and long-term remission is uncommon. Furthermore, few patients are candidate to allogeneic stem cell transplantation (AlSCT), a potentially curative approach...

BACKGROUND: We evaluated health-related quality of life (HRQoL) in patients with chronic lymphocytic leukemia (CLL) receiving first-line chemoimmunotherapy in the GIBB single-arm, Phase II study of obinutuzumab plus bendamustine (BG). MATERIALS AND METHODS: Patients received six 28-day cycles of BG and were followed for up to 27 months. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) and EORTC QLQ Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) questionnaires...

BACKGROUND: When treating indolent B-cell lymphoma, combining continuously administered oral phosphatidylinositol 3-kinase (PI3K) inhibitors with immunochemotherapy has been associated with toxicity. CHRONOS-4 (Phase III; NCT02626455) investigates the intravenous, intermittently administered pan-class I PI3K inhibitor copanlisib in combination with rituximab plus bendamustine (R-B) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed indolent B-cell lymphoma...

INTRODUCTION: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia. We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies. METHODS: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months...