Rare metastatic primary intra-abdominal follicular dendritic cell sarcoma poorly responsive to chemotherapy: A case report

Background@#Follicular dendritic cell sarcoma (FDCS) accounts for about 0.4% of soft tissue sarcomas. Approximately onethird of cases occur in extranodal sites and about 28% of extranodal FDCS may metastasize. Intra-abdominal occurrence is rare and there is limited published data to guide oncologists on how to best treat this malignancy.@*Case Presentation@#This is a case of a 33-year-old female who came in due to incidental finding of a left supraclavicular mass with 2-year history of early satiety. Neck node biopsy revealed a poorly differentiated malignant tumor with positive staining for CD21, CD23, vimentin and S100 consistent with FDCS. PET-CT revealed an intensely FDG-avid large mass in the left upper abdomen with signs of necrosis and mass effect. The patient was given three different chemotherapy regimens that included (1) gemcitabine/docetaxel, (2) single agent doxorubicin and (3) ifosfamide/etoposide, but she progressed on all these. Off-label use of bendamustine was then offered and after just the first cycle, the patient reportedly regained strength and was able to get up from wheelchair with noted interval decrease in size of the cervical mass. Unfortunately, the patient deteriorated and succumbed to infection and multiple pulmonary embolisms.@*Conclusion@#Intra-abdominal FDCS is a rare malignancy with heterogenous outcomes with no uniform treatment strategy at present. Molecular tumor board discussion and multi-disciplinary approach in extranodal FDCS is important in the diagnosis and management. Patients with multiple poor prognostic factors are at risk for tumor recurrence, metastasis, and death.

Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Safety and efficacy of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with relapsed/refractory lymphoma

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.

Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.

Informe de evaluación científica basada en la evidencia disponible: mieloma múltiple / Scientific evaluation report based on available evidence: multiple myeloma

INTRODUCCIÓN: El mieloma múltiple (MM) se caracteriza por la proliferación neoplásica de células plasmáticas que producen una inmunoglobulina monoclonal, estas células plasmáticas proliferan en la médula ósea y, frecuentemente, dan como resultado una extensa destrucción esquelética con lesiones osteolíticas, osteopenia y / o fracturas patológicas. La sospecha diagnóstica se inicia, generalmente debido a la presencia de dolor óseo con lesiones líticas, aumento de la concentración sérica total de proteínas o presencia de una proteína monoclonal en orina o suero, signos o síntomas sistémicos sugestivos de malignidad como anemia inexplicada, hipercalcemia, insuficiencia renal aguda con un urinálisis suave o raramente el síndrome nefrótico debido a la amiloidosis de cadena ligera de inmunoglobulina concurrente, pudiendo presentarse de forma copulativa. Es importante distinguir MM tanto de otras causas de las presentaciones clínicas anteriores, como de otras discrasias de células plasmáticas, para fines de pronóstico y tratamento. TECNOLOGÍAS ANALIZADAS: Bortezomib / Daratumumab / Plerixafor / Lenalidomida / Bendamustina. EFICACIA DE LOS TRATAMIENTOS: -Bortezomib: La adición de bortezomib al tratamiento del mieloma múltiple disminuye la mortalidad. En cuanto a los efectos adversos, la adición de bortezomib aumenta el riesgo de éstos. ­ Daratumumab: La adición de daratumumab al tratamiento del mieloma múltiple podría disminuir la mortalidad, pero la certeza de la evidencia es baja. En cuanto a los efectos adversos, estos no son reportados. ­ Plerixafor: La adición de perixafor al tratamiento del mieloma múltiple podría tener poco o nulo efecto sobre la mortalidad, pero la certeza de la evidencia es baja. En cuanto a los efectos adversos la adición de plerixafor probablemente no se asocia a efectos adversos, o estos son mínimos. ­Lenalidomida: La adición de lenalidomida al tratamiento del mieloma múltiple probablemente no disminuye la mortalidad. En cuanto a los efectos adversos la adición de lenalidomida aumenta los estos efectos grado 3 y 4. ­Bendamustina: No se encontró evidencia sobre la eficacia de la adición de bendamustina al tratamiento del mieloma múltiple. En cuanto a los efectos adversos, tampoco se encontraron estudios que evaluaran la seguridad de la adición de bendamustina. ANÁLISIS ECONÓMICO: Para Bortezomib se consideran los pacientes que logran una remisión completa de células cancerígenas, estimada aproximadamente en un 40%, junto con los que padecen mieloma múltiple y no logran remisión completa de la enfermedad, estimada aproximadamente en un 60% (2). Por lo que el impacto presupuestario proyectado para el año 2018 para pacientes que logran remisión y los que no remiten es de $MM 1.491 y $MM 4.473 respectivamente. Para Bendamustina se considera la cantidad de pacientes que logran una remisión completa de células cancerígenas, estimada aproximadamente en un 40%, junto con la población que padece mieloma múltiple y que son refractarios o tiene una recaída, estimada aproximadamente en un 60% (2). Esto traducido en cantidad de personas aproximadas es 163 y 245, respectivamente, por lo que se proyecta un impacto presupuestario para el año 2018 de $MM 971 para pacientes con remisión completa y de $MM 2.185 para pacientes refractarios al tratamiento. Para Daratumumab no se encuentra evidencia de evaluaciones económicas de este tratamiento para pacientes con mieloma múltiple. El impacto presupuestario proyectado para el año 2018 es de $MM 44.775. Para Lenalidomida se considera la cantidad de pacientes que con anterioridad cuenten con un tratamiento previo a tratarse con lenalidomida, para esto se considera al 60% de la población que desarrolla la enfermedad pero que con un primer diagnóstico no ha sido posible la remisión completa de su cuerpo. El número de personas correspondientes a este 60% es 245 (2). El impacto presupuestario proyectado para el año 2018 es de $MM 3.232. Para el tratamiento con Plerixafor, el impacto presupuestario proyectado para el año 2018 es de $MM 556. CONCLUSIÓN: Se hace presente que la oferta recibida en este Ministerio de Salud, contempla mecanismo de riesgo compartido, por lo que se sugiere que la CENABAST en una eventual compra, considere dicha modalidad contractual. Asimismo, cabe indicar que la determinaicón del Precio Máximo Industrial se ha ajustado a derecho. Por último y sin perjuicio de lo antes señalado, es dable agregar que, conforme al análisis efectuado al presente informe, éste se ajusta a derecho.

Bendamustine in heavily pre-treated multiple myeloma patients: Results of a retrospective analysis from the Korean Multiple Myeloma Working Party

BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed. The median time from diagnosis to bendamustine treatment was 3.8 years, and the median patient age was 63 years (range, 38‒77 yr). The responses to the last treatment before bendamustine were refractory disease (N=52, 80%) or disease progression from partial response (N=13, 20%). Twenty-three patients responded to the treatment, with an overall response rate of 35% (23/65), and the median number of bendamustine treatment cycles was two (range, 1‒5 cycles). The median overall survival after bendamustine treatment was 5.5 months and the overall survival rate in responders to bendamustine was significantly better than that in non-responders (P=0.036). CONCLUSION: Bendamustine may be a potential salvage treatment to extend survival in a select group of heavily pre-treated patients with relapsed or refractory myeloma.

Salvage chemotherapy with R-BAD (rituximab, bendamustine, cytarabine, and dexamethasone) for the treatment of relapsed primary CNS lymphoma

No abstract available.