Cost-Effectiveness of Zanubrutinib Versus Bendamustine and Rituximab in Patients With Untreated Chronic Lymphocytic Leukemia.

PURPOSE: Zanubrutinib, a potent and specific irreversible Bruton's tyrosine kinase inhibitor, has proven to be effective in untreated chronic lymphocytic leukemia (CLL), whether used alone or in combination with other therapies. Here, we compared the cost-effectiveness of zanubrutinib with bendamustine-rituximab (R-bendamustine) to determine its effectiveness as the first-line treatment for Chinese patients with untreated CLL. METHODS: The evaluation utilized a partitioned survival model, constructed using TreeAge Pro 2011 software, incorporating data from SEQUOIA trial (NCT03336333). Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. In this analysis, the quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and lifetime cost were calculated from the Chinese health care system perspective. Sensitivity analyses, including 1-way analysis and probabilistic sensitivity analysis, were carried out to explore the uncertainty of the modeling results. Additionally, several scenario analyses, including different zanubrutinib price calculation and 20-year time horizon, were evaluated. FINDINGS: The findings revealed that zanubrutinib had an incremental cost-effectiveness ratio of $58,258.18 per additional QALYs gained compared with bendamustine-rituximab, with zanubrutinib being cost-effective only if its price was reduced by more than 30%. Research indicated that zanubrutinib achieved at least a 3.70% probability of cost-effectiveness at the threshold of $38,223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to the utility of progressed disease. IMPLICATIONS: The study highlighted the importance of considering the cost-effectiveness of zanubrutinib at its current price point for patients with untreated CLL in China, emphasizing the need for further assessment and potential pricing adjustments to enhance its economic viability in clinical practice.

Efficacy and Safety of Bendamustine-Rituximab as Frontline Therapy for Indolent Non-Hodgkin Lymphoma: A Real-World, Single-Center, Retrospective Study.

Background The use of bendamustine with an anti-CD20 monoclonal antibody as frontline therapy for indolent non-Hodgkin lymphoma (NHL) has become a standard of care. We aimed to evaluate the real-world efficacy and safety of bendamustine-rituximab (BR) frontline therapy for indolent NHL. Patients and methods Patients with indolent NHL treated with frontline BR therapy in Hôpital du Sacré-Coeur de Montréal, from January 2015 to August 2018 were included in this retrospective study. Results Our cohort included 42 adults with a median age of 63 years. Follicular lymphoma was the most common histology (n = 31, 74%). Most patients had advanced disease (Lugano stage III or IV, 88%). The overall response rate was 84% (complete response = 62% and partial response = 22%). Median progression-free survival (PFS) was not reached. At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events were observed in 17 patients (40%). Most were grade 1 and 2 events (84%). One case of grade 5 progressive multifocal leukoencephalopathy related to John Cunningham (JC) virus reactivation was observed. The most common non-infectious-related adverse events were mild nausea and fatigue. Conclusions The efficacy and safety of BR treatment for indolent NHL were comparable in our real-life cohort compared to prior studies. This supports BR as a standard of care for indolent NHL. Future studies should assess whether the use of granulocyte-colony stimulating factors as primary prophylaxis effectively mitigates the hematological and infection-related adverse events related to BR therapy.

A phase Ib trial of isatuximab, bendamustine, and prednisone in relapsed/refractory multiple myeloma.

INTRODUCTION: Patients with triple-class refractory (TCR) multiple myeloma (MM) often need cytoreductive chemotherapy for rapid disease control. Bendamustine is an outpatient-administered, bifunctional alkylator and isatuximab is an anti-CD38 monoclonal antibody with unique cytotoxicity characteristics. We hypothesized that isatuximab-bendamustine-prednisone would be well-tolerated regimen in TCR MM, and conducted single-center, phase Ib, investigator-initiated study. PATIENTS/METHODS: Patients had TCR MM and last daratumumab exposure ≥ 6 weeks. This study was conducted as a 3 + 3 design to establish the maximally tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Isatuximab 10 mg/kg IV was administered weekly (cycle 1), and every 2 weeks thereafter. Bendamustine was administered on days 1 and 2 at 3 dose levels (DL): 50, 75, and 100 mg/m2. Methylprednisolone was administered as 125 mg on day 1 and prednisone 60 mg days 2-4. Common definitions were used for DLTs, adverse events (CTCAE v 5.0), and disease response. RESULTS: Fifteen patients were treated (3 DL1, 6 DL2, 6 DL3). Median age was 71, 53% had high-risk cytogenetics, and 34% had prior BCMA-targeting therapy. One DLT was observed at DL2 (Grade 3 thrombocytopenia plus bleeding). There were no Grade 5 treatment-related AEs. The MTD was not reached. The overall response rate was 20% (3/15) including one stringent complete response. The median PFS was 2.5 months (95% CI 0.9-4.1 months). CONCLUSION: We demonstrated the safety and tolerability of isatuximab-bendamustine-prednisone. Toxicities were mild and manageable with limited intervention. The study was discontinued due to slow accrual. However, we observed responses even among highly refractory patients. CLINICAL TRIAL REGISTRATION: This study was registered on clinicaltrials.gov as NCT04083898 on 9/6/2019.

Lymphocyte recovery after bendamustine therapy in patients with mantle cell lymphoma. Results of a retrospective analysis and prognostic impact in the CAR-T era.

Bendamustine in combination with rituximab (BR) or with rituximab and cytarabine (R-BAC) is the standard first-line immunochemotherapy in mantle cell lymphoma (MCL) for elderly patients and patients ineligible for intensive regimens or autologous transplantation. As bendamustine causes prolonged lymphopenia and the literature lacks evidence of its persistence in patients with MCL, this retrospective analysis aims to estimate the lymphocyte recovery time, also in view of potential immunotherapy with CAR-T cells. Data were collected from 44 consecutive MCL patients who received bendamustine (BR or R-BAC) as first-line therapy at the Hematology Unit of Sapienza University Hospital between May 2011 and April 2022. Twenty patients (45%) were treated with R-BAC and 24 (55%) with BR. At baseline, the median lymphocyte count was 1795/µl (range: 370-11730/µL). One month after the end of therapy, it was 450/µl (range: 50-3300/µl) and 3 months after 768/µl (range: 260-1650/µl). After 6 and 9 months, we observed a gradual increase in median lymphocyte count of 900/µl (range: 370-2560/µl and 130-2770/µl, respectively). After 12 months median lymphocyte count was 1256/µl (range: 240-4140/µl). Median lymphocyte count at 1, 3, 6, and 9 months post-treatment was significantly lower than baseline but showed recovery by the 12 months. This finding is crucial for MCL patients considering CAR-T cell therapy, suggesting a minimum 9-month interval between bendamustine administration and leukapheresis.

Early Toxicity and Efficacy of Four Different Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Patients With Lymphoma: Impact of Drug Shortages in a Resource-Constrained Country.

High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.

Clinical Outcome of Patients Receiving Rituximab in Combination with Bendamustine in Indolent B-cell Lymphomas: A Single-center Institutional Study.

Introduction: Indolent non-Hodgkin's lymphomas (NHLs) are a diverse category of malignancies characterized by a chronic relapsing-remitting disease course. In the modern era, patients usually receive a combination of bendamustine plus rituximab as the initial therapy, otherwise known as an R-Benda regimen. While clinical trials have demonstrated R-Benda to be superior to other regimens, our study aims to provide insight into real-world outcomes of R-Benda therapy. Materials and Methods: We conducted a retrospective study for January 2015-July 2022 among patients receiving R-Benda for indolent NHLs at the Aga Khan University Hospital, Karachi, Pakistan. All patients underwent pre- and post-treatment assessment through positron emission tomography scan and computed tomography (CT) imaging. The response to treatment was assessed, and the overall survival (OS) and progression-free survival (PFS) were assessed using a Kaplan-Meier survival analysis. Results: We enrolled 118 patients, out of which the majority were elderly males (64%). The 2-year follow-up rate was 76.3% (n = 90), and the median follow-up time was 29 months. The most common histopathology encountered was follicular lymphoma (52%) presenting with stage IV disease (56%). Approximately 73% experienced a complete metabolic response to the treatment. Of these, 31.4% subsequently experienced a relapse. In addition, 17.7% of patients underwent a partial response, while 7% had refractory disease. The mean OS was 140 months (95% CI: 120-160), while the lower quartile value was 50 months. On the other hand, the median PFS was 80 months (95% CI: 43-N/A). Conclusion: Our study demonstrated that patients on R-Benda had good clinical outcomes, with the vast majority living beyond 50 months. Moreover, 76.1% had no disease progression for the first 2 years. It adds to the existing body of literature that demonstrates that in real-world experience, the outcomes of R-Benda treatment are better than those reported by earlier randomized-control trials.

Risk and impact of cytomegalovirus infection in lymphoma patients treated with bendamustine.

Bendamustine is used to treat lymphoma with excellent efficacy but is known for its immunosuppressive effect. Cytomegalovirus (CMV) reactivation after bendamustine use has been reported. We aim to address the impact of CMV infection in lymphoma patients treated with bendamustine-containing regimens. We retrospectively analyzed lymphoma patients at Taipei Veterans General Hospital in Taiwan between September 1, 2010, and April 30, 2022. Clinically significant CMV infection (CS-CMVi) was defined as the first CMV reactivation after bendamustine use necessitating CMV therapy. Patients' baseline characteristics and laboratory data were recorded. The primary endpoint of the study was CS-CMVi. A time-dependent covariate Cox regression model was used to estimate the risk factors of CS-CMVi and mortality. A total of 211 lymphoma patients treated with bendamustine were enrolled. Twenty-seven (12.8%) had CS-CMVi. The cumulative incidence was 10.1 per 100 person-years during the three-year follow-up period. In the multivariate analysis, lines of therapy before bendamustine ≥ 1 (95% CI 1.10-24.76), serum albumin < 3.5 g/dL (95% CI 2.63-52.93), and liver disease (95% CI 1.51-28.61) were risk factors for CS-CMVi. In conclusion, CS-CMVi (95% confidence interval [CI] 1.23-10.73) was one of the major independent risk factors of mortality. Lines of therapy before bendamustine ≥ 1, hypoalbuminemia, and liver disease were risk factors for CS-CMVi in lymphoma patients treated with bendamustine.

The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody.

BACKGROUND: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. METHODS: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. RESULTS: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. CONCLUSIONS: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.

Symptomatic Follicular Lymphoma: Complete Remission After Chemoimmunotherapy with Bendamustine-Rituximab.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in Western countries after diffuse large B-cell lymphoma. Most patients with FL present with asymptomatic disease. Survival rates have been rising over time mainly due to advancing therapeutic strategiesA-51-year-old male with a history of well-controlled diabetes mellitus treated with insulin presented to the policlinic of hematology-medical oncology with worsening right inguinal lymphadenopathy for >3 months. He had no complaints of prolonged fever, night sweat, or weight loss. Initial physical examination revealed a healthy male with bulky right inguinal lymphadenopathy. The patient was then referred to a surgeon, and excisional biopsy of the enlarged right inguinal lymph nodes was performed. Therefore, stage II bulky symptomatic low-grade FL was established. We administered chemoimmunotherapy with rituximab and bendamustine every 3 weeks for six cycles. The patient tolerated the treatment well and completed six cycles of chemoimmunotherapy, and the follow-up FDG PET/CT showed complete remission of the disease.The patient achieved complete remission after series of chemoimmunotherapy with Bendamustine-Rituximab. Future assessment is still required for this patient to ensure the remission status of the lymphoma.

Comparable efficacy of oral bendamustine versus intravenous administration in treating hematologic malignancies.

PURPOSE: The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine and a novel orally administered (PO) bendamustine agent that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles. METHODS: Pharmacokinetics of IV versus PO bendamustine were determined by analysis of plasma samples collected from NSG mice treated with either IV or PO bendamustine. Plasma samples were analyzed using liquid chromatography-mass spectrometry following a liquid-liquid extraction to determine peak bendamustine concentration, area under the concentration-time curve, and the half-life in-vivo. In-vitro cytotoxicity of bendamustine against human non-Hodgkin Burkitt's Lymphoma (Raji), multiple myeloma (MM.1s), and B-cell acute lymphoblastic leukemia (RS4;11) cell lines was determined over time using MTS assays. Luciferase-tagged versions of the aforementioned cell lines were used to determine in-vivo bendamustine cytotoxicity of IV versus PO bendamustine at two different doses. RESULTS: Bendamustine at a high dose in-vitro causes cell death. There was no significant difference in antitumor activity between IV and novel PO bendamustine at a physiologically relevant concentration in all three xenograft models. In-vivo pharmacokinetics showed the oral bioavailability of bendamustine in mice to be 51.4%. CONCLUSIONS: The novel oral bendamustine agent tested exhibits good oral bioavailability and systemic exposure for in-vivo antitumor efficacy comparable to IV bendamustine. An oral bendamustine formulation offers exciting clinical potential as an additional method of administration for bendamustine and warrants further evaluation in clinical studies.

Synergistic Effect of Venetoclax and Bendamustine in Early T-cell Precursor Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy. MATERIALS AND METHODS: Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package. RESULTS: Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score: 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55. CONCLUSION: The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.

[The Reduction of CD4+ T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy].

OBJECTIVE: To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. METHODS: The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. RESULTS: The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OS（P ＞0.05）. Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. CONCLUSION: The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.

Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma: a single-institution experience.

Extranodal marginal zone lymphoma (EMZL) encompasses 70% of cases of marginal zone lymphoma. Frontline bendamustine and rituximab (BR) were derived from trials involving other indolent non-Hodgkin's lymphomas. Only one trial has evaluated frontline BR prospectively in EMZL. This retrospective study reports outcomes among EMZL patients receiving frontline BR. Twenty-five patients were included with a median age of 69 years (40-81). Five (20.0%) patients had stage I/II disease, and 20 (80.0%) had stage III/IV disease. The median number of cycles was 6.0 (3.0-6.0). Maintenance rituximab was administered to 10 (41.7%) individuals. Overall response rate (ORR) was 100.0% (60.0% complete response, 40.0% partial response). Medians of overall survival and progression-free survival were not reached. The estimated 2-year progression-free survival was 85.2% and overall survival was 100.0%. Four (16.6%) patients had infections related to treatment; 3 (12.0%) transformed to diffuse large B-cell lymphoma; 5 (20.8%) had a relapse or progression of EMZL; and 3 (12.0%) died unrelated to BR. BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

Cost-effectiveness analysis of mosunetuzumab for treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in the United States.

AIMS: Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective. MATERIALS AND METHODS: A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len. LIMITATIONS: Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties. CONCLUSION: Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

Disseminated tuberculosis after Polatuzumab-Vedotin based chemoimmunotherapy in a patient with Burkitt's lymphoma.

This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol) despite appropriate chemoprophylaxis. A 48-year-old male with refractory Burkitt's lymphoma (BKL) was treated with PBR protocol. At baseline, the patient had a negative QuantiFERON test result, which turned out to be positive prior to starting PBR. He received chemoprophylaxis for 9 months and was compliant with treatment. One year later, he was admitted with COVID-19 pneumonia and was treated according to the protocol. His symptoms persisted for 1 month. Investigations yielded disseminated TB-infiltrated bone marrow and pleura. Downstream B-cell and T-cell depletion secondary to CD20 and CD79b antagonism may potentially explain the increased risk of TB reactivation associated with the combination of PV and rituximab. Further research is necessary to monitor the risk of TB reactivation among patients receiving a combination of PV and rituximab, especially in endemic areas with high prevalence and incidence of TB.

A Case of Primary Adrenal Insufficiency Triggered by Cytomegalovirus Infection after Obinutuzumab plus Bendamustine Therapy for Follicular Lymphoma.

A 69-year-old man was diagnosed with follicular lymphoma (Grade 3A). Obinutuzumab combined with bendamustine (OB) therapy was initiated as salvage chemotherapy. Nausea, abdominal pain, and hyponatremia appeared after six courses of OB therapy; cytomegalovirus (CMV) enteritis with primary adrenal insufficiency (PAI) was a complication. Ganciclovir and hydrocortisone were administered, and the clinical findings improved. PAI caused by CMV infection has mainly been reported in patients with acquired immunodeficiency syndrome. In the present case, the PAI triggered by CMV infection led to immunodeficiency after chemotherapy.

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

Safety and efficacy of parsaclisib in combination with rituximab, bendamustine + rituximab, or ibrutinib in patients with previously treated B-cell lymphoma: analysis of a phase 1 dose-finding study (CITADEL­112).

Parsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas.

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.