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Technology in Cancer Research &... 20241q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in...
OBJECTIVE
1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp.
METHODS
Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed.
RESULTS
Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% 37.0%, = 0.034), lower disease progression rate (31.8% 70.3%, = 0.002), longer sustained remission (median 49.7 months 18.3 months, = 0.030), and longer PFS (median 61.9 months 22.9 months, = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% 77.8%, = 0.532) or CR (27.3% 13.0%, = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (= 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (= 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (= 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS.
CONCLUSIONS
When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.
Topics: Humans; Bortezomib; Lenalidomide; Multiple Myeloma; Female; Male; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Aged; Chromosomes, Human, Pair 1; Adult; Retrospective Studies; Prognosis; Treatment Outcome; Chromosome Aberrations; Aged, 80 and over; Dexamethasone
PubMed: 38759699
DOI: 10.1177/15330338241252605 -
Polish Archives of Internal Medicine May 2024
Health-related quality of life in patients with multiple myeloma treated in the phase 3 ATLAS trial of post-transplant maintenance with carfilzomib, lenalidomide, dexamethasone or lenalidomide alone.
PubMed: 38747414
DOI: 10.20452/pamw.16749 -
Cancer Medicine May 2024Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown...
BACKGROUND
Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single-center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly-diagnosed PCNSL.
METHODS
Sixty-nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment.
RESULTS
After a median follow-up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression-free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life.
CONCLUSIONS
The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.
Topics: Humans; Lenalidomide; Female; Male; Middle Aged; Retrospective Studies; Central Nervous System Neoplasms; Aged; Methotrexate; Maintenance Chemotherapy; Adult; Lymphoma; Progression-Free Survival; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38738459
DOI: 10.1002/cam4.7193 -
Oncology Letters Jun 2024Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with varying characteristics, in terms of genomic variation, cell morphology and clinical presentation....
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with varying characteristics, in terms of genomic variation, cell morphology and clinical presentation. At present, only ~66% of patients are cured with initial treatment and those with refractory DLBCL exhibit a poor prognosis. Thus, further investigations into novel effective treatment options for DLBCL are required. The present study reports the case of a patient resistant to multiple therapies, including rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus enzastaurin (trial no. CTR20171560), GemOx plus lenalidomide and selinexor (trial no. ATG-010-DLBCL-001). The patient harbored a amplification, as identified via next-generation sequencing (NGS), and exhibited a high programmed death-ligand 1 Tumor Proportion Score of up to 95%. Consequently, the patient was treated with sintilimab monotherapy and the response lasted for 12 months of follow-up without major immune-related adverse events. This case highlights the role of NGS technology in selecting treatment options for refractory DLBCL. Furthermore, the results of the present study suggest that sintilimab may have potential in the treatment of patients with refractory DLBCL.
PubMed: 38736746
DOI: 10.3892/ol.2024.14423 -
Cancers Apr 2024FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in... (Review)
Review
FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.
PubMed: 38730656
DOI: 10.3390/cancers16091706 -
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 -
MedRxiv : the Preprint Server For... Apr 2024Early therapeutic intervention in high-risk SMM (HR-SMM) has demonstrated benefit in previous studies of lenalidomide with or without dexamethasone. Triplets and...
Long-Term Follow-Up Defines the Population That Benefits from Early Interception in a High-Risk Smoldering Multiple Myeloma Clinical Trial Using the Combination of Ixazomib, Lenalidomide, and Dexamethasone.
BACKGROUND
Early therapeutic intervention in high-risk SMM (HR-SMM) has demonstrated benefit in previous studies of lenalidomide with or without dexamethasone. Triplets and quadruplet studies have been examined in this same population. However, to date, none of these studies examined the impact of depth of response on long-term outcomes of participants treated with lenalidomide-based therapy, and whether the use of the 20/2/20 model or the addition of genomic alterations can further define the population that would benefit the most from early therapeutic intervention. Here, we present the results of the phase II study of the combination of ixazomib, lenalidomide, and dexamethasone in patients with HR-SMM with long-term follow-up and baseline single-cell tumor and immune sequencing that help refine the population to be treated for early intervention studies.
METHODS
This is a phase II trial of ixazomib, lenalidomide, and dexamethasone (IRD) in HR-SMM. Patients received 9 cycles of induction therapy with ixazomib 4mg on days 1, 8, and 15; lenalidomide 25mg on days 1-21; and dexamethasone 40mg on days 1, 8, 15, and 22. The induction phase was followed by maintenance with ixazomib 4mg on days 1, 8, and 15; and lenalidomide 15mg d1-21 for 15 cycles for 24 months of treatment. The primary endpoint was progression-free survival after 2 years of therapy. Secondary endpoints included depth of response, biochemical progression, and correlative studies included single-cell RNA sequencing and/or whole-genome sequencing of the tumor and single-cell sequencing of immune cells at baseline.
RESULTS
Fifty-five patients, with a median age of 64, were enrolled in the study. The overall response rate was 93%, with 31% of patients achieving a complete response and 45% achieving a very good partial response or better. The most common grade 3 or greater treatment-related hematologic toxicities were neutropenia (16 patients; 29%), leukopenia (10 patients; 18%), lymphocytopenia (8 patients; 15%), and thrombocytopenia (4 patients; 7%). Non-hematologic grade 3 or greater toxicities included hypophosphatemia (7 patients; 13%), rash (5 patients; 9%), and hypokalemia (4 patients; 7%). After a median follow-up of 50 months, the median progression-free survival (PFS) was 48.6 months (95% CI: 39.9 - not reached; NR) and median overall survival has not been reached. Patients achieving VGPR or better had a significantly better progression-free survival (p<0.001) compared to those who did not achieve VGPR (median PFS 58.2 months vs. 31.3 months). Biochemical progression preceded or was concurrent with the development of SLiM-CRAB criteria in eight patients during follow-up, indicating that biochemical progression is a meaningful endpoint that correlates with the development of end-organ damage. High-risk 20/2/20 participants had the worst PFS compared to low- and intermediate-risk participants. The use of whole genome or single-cell sequencing of tumor cells identified high-risk aberrations that were not identified by FISH alone and aided in the identification of participants at risk of progression. scRNA-seq analysis revealed a positive correlation between MHC class I expression and response to proteasome inhibition and at the same time a decreased proportion of GZMB+ T cells within the clonally expanded CD8+ T cell population correlated with suboptimal response.
CONCLUSIONS
Ixazomib, lenalidomide and dexamethasone in HR-SMM demonstrates significant clinical activity with an overall favorable safety profile. Achievement of VGPR or greater led to significant improvement in time to progression, suggesting that achieving deep response is beneficial in HR-SMM. Biochemical progression correlates with end-organ damage. Patients with high-risk FISH and lack of deep response had poor outcomes. ClinicalTrials.gov identifier: (NCT02916771).
PubMed: 38699307
DOI: 10.1101/2024.04.19.24306082 -
Cancer Medicine May 2024Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory...
BACKGROUND
Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies.
METHODS
This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023.
RESULTS
The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009).
CONCLUSIONS
In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.
Topics: Humans; Multiple Myeloma; Thalidomide; Male; Female; Retrospective Studies; Middle Aged; Aged; China; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal; Progression-Free Survival; Aged, 80 and over; Treatment Outcome; Adult; Neoplasm Recurrence, Local; Drug Resistance, Neoplasm
PubMed: 38698679
DOI: 10.1002/cam4.7232 -
BMC Medical Research Methodology May 2024Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance...
BACKGROUND
Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence is rising, yet it remains incurable and represents a significant disease burden. Clinical registries can provide important information on management and outcomes, and are vital platforms for clinical trials and other research. The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR) was developed to monitor and explore variation in epidemiology, treatment regimens and their impact on clinical outcomes across this region. Here we describe the registry's design and development, initial data, progress and future plans.
METHODS
The APAC MRDR was established in 2018 as a multicentre collaboration across the Asia-Pacific, collecting prospective data on patients newly diagnosed with MM, MGUS, PCL and plasmacytoma in Korea, Singapore, Malaysia and Taiwan, with China recently joining. Development of the registry required a multidisciplinary team of clinicians, researchers, legal and information technology support, and financial resources, as well as local clinical context from key opinion leaders in the APAC region. Written informed consent is obtained and data are routinely collected throughout treatment by hospital staff. Data are stored securely, meeting all local privacy and ethics requirements. Data were collected from October 2018 to March 2024.
RESULTS
Over 1700 patients from 24 hospitals have been enrolled onto the APAC MRDR to date, with the majority (86%) being newly diagnosed with MM. Bortezomib with an immunomodulatory drug was most frequently used in first-line MM therapy, and lenalidomide-based therapy was most common in second-line. Establishment and implementation challenges include regulatory and a range of operational issues.
CONCLUSION
The APAC MRDR is providing 'real-world' data to participating sites, clinicians and policy-makers to explore factors influencing outcomes and survival, and to support high quality studies. It is already a valuable resource that will continue to grow and support research and clinical collaboration in MM and related diseases across the APAC region.
Topics: Multiple Myeloma; Humans; Registries; Asia; Male; Female; Taiwan; Malaysia; Singapore; Middle Aged; Republic of Korea; Prospective Studies
PubMed: 38698331
DOI: 10.1186/s12874-024-02227-0 -
Cureus Mar 2024Multiple myeloma (MM) is a neoplastic proliferation of plasma cells in bone marrow. Pharmacotherapy for the management of patients with MM includes drug classes like...
Multiple myeloma (MM) is a neoplastic proliferation of plasma cells in bone marrow. Pharmacotherapy for the management of patients with MM includes drug classes like proteasome inhibitors, monoclonal antibodies, immunomodulators, alkylating agents, steroids, etc. We present a case of new-onset heart failure with reduced ejection fraction (HFrEF) in a patient with previously normal ejection fraction after treatment with a cyclophosphamide, bortezomib, and dexamethasone (CyBorD) chemotherapeutic regimen. An echocardiogram done after the completion of nine cycles of chemotherapy in a period of about 4.5 months showed severely decreased left ventricular systolic function with an ejection fraction of only 15-20% and grade I diastolic dysfunction. Cardiac catheterization showed no angiographic evidence of vessel occlusion or epicardial disease. HFrEF was managed with the initiation of guideline-directed medical therapy with cardiology clinic follow-up, and the patient was discharged with a plan to start a lenalidomide-based chemotherapeutic regimen with oncology clinic follow-up. It is, therefore, imperative to perform a thorough cardiovascular assessment before initiation of chemotherapy, complemented by periodic and recurrent assessments of cardiovascular function during and after completion of the treatment course, for early detection and prevention of potentially severe cardiovascular toxicities in patients with MM.
PubMed: 38665754
DOI: 10.7759/cureus.56966