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Clinical Case Reports May 2024This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol)...
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.
PubMed: 38721565
DOI: 10.1002/ccr3.8838 -
Journal of Medical Economics May 2024Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL)...
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.
PubMed: 38712895
DOI: 10.1080/13696998.2024.2352820 -
Frontiers in Medicine 2024Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. Waldenström macroglobulinemia (WM) with systemic...
Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. Waldenström macroglobulinemia (WM) with systemic amyloidosis as the main manifestation is even rarer. The patient in this study presented with recurrent diarrhea and had not been diagnosed in other hospitals on multiple occasions. Later, his diarrhea worsened and was accompanied by sunken edema of both lower limbs and dizziness. Renal biopsy showed deposits of PAS light-staining material in the glomeruli, interstitium, and small arteries, which stained positively with Congo red. Cardiac ultrasound showed interventricular septum thickening of 17 mm, right ventricular wall myocardial thickening of approximately 0.6 cm, and septal thickening of approximately 0.5 cm, considering myocardial amyloidosis. Electromyography showed abnormal peripheral nerve conduction. Lymphoplasmacytic cells were found in the bone marrow. Taken together, he was diagnosed with WM. He was treated with a BR (Bendamustine + Rituximab) regimen. After 6 courses, the patient's discomfort was relieved, his weight gained 5 kg, the level of serum IgM and dFLC decreased, and cardiac and renal assessments were more relieved. The patient has been followed up for more than 1 month.
PubMed: 38707188
DOI: 10.3389/fmed.2024.1340553 -
Cancer Reports (Hoboken, N.J.) Apr 2024Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct...
BACKGROUND
Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct histopathological entities such as glomerular (amyloidotic and non-amyloidotic), tubulo-interstitial and non-paraprotein mediated renal damage. In this context, disease characterization, management, relationship between renal, and hematological response have been poorly explored. We collected clinical, genetic and laboratory data of seven cases of biopsy-proven renal involvement by WM managed at our academic center and focused on three cases we judged paradigmatic discussing their histopathological patterns, clinical features, and therapeutic options.
CASE
In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. In our series AL Amyloidosis (n = 3/7) and tubulo-interstitial infiltration by lymphoma cells (n = 3/7) were the two more represented entities. BTKi did not seem to improve renal function (Case 1), while bortezomib-based regimens demonstrated a beneficial activity on the hematological and organ response, even when used as second-line therapy after chemoimmunotherapy (Case 3) and also with coexistence of anti-MAG neuropathy (Case 2). In case of poor response to bortezomib, standard chemoimmunotherapy (CIT), such as rituximab-bendamustine, represents an effective option (Case 1, 6, and 7). In our series, CIT generates durable responses more frequently in cases with amyloidogenic renal damage (Case 1, 5, and 7).
CONCLUSION
In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. Studies with higher numerosity are needed to better clarify the pathological and clinical features of renal involvement during WM and to determine the potential benefit of different therapeutic regimens according to the histopathological subtypes.
Topics: Humans; Waldenstrom Macroglobulinemia; Male; Aged; Female; Middle Aged; Kidney; Biopsy; Bortezomib
PubMed: 38662353
DOI: 10.1002/cnr2.2062 -
Turkish Journal of Haematology :... Apr 2024Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma in Western countries. While FL is generally incurable, standard initial therapies...
Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma in Western countries. While FL is generally incurable, standard initial therapies are associated with high response rates and durable remissions for most patients. In addition, novel targeted agents and immunotherapies are changing the treatment algorithm for patients with relapsed or refractory disease. This review discusses initial staging, prognosis, and treatment options for newly diagnosed and relapsed/refractory FL. Initial treatment options for FL include active surveillance, radiotherapy, rituximab monotherapy, and chemoimmunotherapy. Staging with PET/CT and bone marrow biopsy is crucial for identifying early-stage patients. Most patients with FL will receive chemoimmuntherapy as initial treatment with options including rituximab or obinutuzumab plus CVP, CHOP, bendamustine, or lenalidomide. No significant differences in overall survival have been observed in randomized studies comparing these regimens. Maintenance therapy with rituximab or obinutuzumab in responders to initial chemoimmunotherapy improves progression-free survival. For relapsed/refractory FL, treatment options include chemoimmunotherapy, lenalidomide-based regimens, tazemetostat, chimeric antigent receptor (CAR) T cell therapy (axicabtagene ciloleucel and tisagenlecleucel) and CD3/CD20 bispecific antibodies (BsAbs). Given encouraging outcomes with CAR T cell therapy and BsAbs, multiple trials are testing these highly active agents in earlier lines of therapy and among high-risk patients with early relapse after frontline chemoimmunotherapy. Additonal studies and follow-up are needed to understand how these novel agents may further change treatment algorithms for FL.
PubMed: 38660754
DOI: 10.4274/tjh.galenos.2024.2024.0015 -
Journal of Hematology & Oncology Apr 2024Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products...
Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.
Topics: Humans; Bendamustine Hydrochloride; Middle Aged; Male; Female; Aged; Immunotherapy, Adoptive; Retrospective Studies; Adult; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents, Alkylating; Biological Products; Aged, 80 and over; Treatment Outcome
PubMed: 38644469
DOI: 10.1186/s13045-024-01542-9 -
EJHaem Apr 2024Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL)...
Poor outcomes for trial-ineligible patients receiving polatuzumab for relapsed/refractory diffuse large B-cell lymphoma in routine care: An Australian Lymphoma and Related Diseases Registry project.
Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR-DLBCL have not been replicated in routine care cohorts, as RR-DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR-DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression-free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real-world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.
PubMed: 38633125
DOI: 10.1002/jha2.870 -
Cancers Mar 2024Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for...
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 ( = 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 ( = 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.
PubMed: 38610963
DOI: 10.3390/cancers16071285 -
Cancer Medicine Apr 2024Although initial treatment of diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be effective,...
BACKGROUND
Although initial treatment of diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be effective, up to 50% of patients will develop refractory or relapsed (R/R) disease. This study aimed to provide contemporary data on characteristics, treatment patterns, and outcomes for R/R-DLBCL.
METHODS
Patients with incident (January 2016 to March 2021) DLBCL age ≥18 years who initiated first-line (1L) therapy were identified from the COTA real-world database. Baseline characteristics, treatment patterns, and real-world outcomes, including time to next treatment (rwTTNT) and overall survival (rwOS), were assessed for the study population and by line of therapy (LOT).
RESULTS
A total of 1347 eligible DLBCL patients were identified. Of these, 340 (25.2%) proceeded to receive 2L, of whom 141 (41.5%) proceeded to receive 3L, of whom 51 (36.2%) proceeded to receive 4L+. Most common treatments were R-CHOP in 1L (63.6%), stem cell transplant (SCT) in 2L (17.9%), polatuzumab vedotin, bendamustine, and rituximab (Pola-BR) in 3L (9.9%), and chimeric antigen receptor T-cell therapy (CAR-T) in 4L (11.8%). Treatment patterns were more variable in later LOTs. One- and 3-year rwOS from 1L initiation were 88.5% and 78.4%, respectively. Patients who received later LOTs experienced numerically lower 1- and 3-year rwOS (from 2L initiation: 62.4% and 46.4%, respectively).
CONCLUSIONS
In this real-world analysis, 25.2% of patients experienced R/R-DLBCL after 1L with poor outcomes. Given the findings of this study, there is a high unmet need for novel, safe, and effective treatment options for patients with R/R DLBCL.
Topics: Humans; Adolescent; Rituximab; Treatment Outcome; Lymphoma, Large B-Cell, Diffuse; Cyclophosphamide; Vincristine; Prednisone; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38597118
DOI: 10.1002/cam4.7173 -
Alternative Therapies in Health and... Apr 2024This paper comprehensively analyzes the caregiver burden and its influencing factors on primary caregivers in autologous hematopoietic stem cell transplantation...
This paper comprehensively analyzes the caregiver burden and its influencing factors on primary caregivers in autologous hematopoietic stem cell transplantation (Auto-HSCT) with bendamustine preconditioning. Auto-HSCT refers to the transplantation of cells back to the patient, aiming to eliminate tumor cells and prolong the patient's life. Bendamustine, while enhancing the success rate of transplantation, has drawn considerable attention to the primary caregivers of patients. Due to the complex nature of the transplantation process, patients have diverse caregiving needs, which caregivers must address to support the entire treatment journey. The caregiver burden of primary caregivers is influenced by various factors, including the patient's disease condition, various aspects of the caregiver as an individual, and psychological factors. The article emphasizes the need for personalized care plans and psychological support to minimize caregiver burden and improve overall quality of life. This study has positive implications for optimizing the implementation of Auto-HSCT therapy.
PubMed: 38581336
DOI: No ID Found