bluuebunny/crossref_metadata_2025 huggingface dataset:
Matching-adjusted indirect comparison (MAIC) of zanubrutinib (ZANU) versus ibrutinib (IBRU) in relapsed/refractory marginal zone lymphoma (R/R MZL).
Authors: Thieblemont Catherine , Wang Kaijun , Keeping Sam , Zhang Ina , Yang Keri , Tang Boxiong , Mohseninejad Leyla
Published: June 2023

e19527

Background: ZANU is a Bruton tyrosine kinase inhibitor (BTKi) that has been evaluated for the treatment of R/R MZL in two phase 2, single-arm trials (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. IBRU, a first-generation BTKi, has also been evaluated for R/R MZL in a phase 2, single-arm trial (PCYC-1121, n=60 [Noy et al., Blood 2017; Noy et al., Blood Adv 2020]). Here, we conducted an unanchored MAIC to estimate the comparative efficacy of ZANU vs IBRU in R/R MZL. Methods: The MAIC utilized study-level data from PCYC-1121 and pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. A logistic propensity score model was used to estimate weights for patients in the ZANU trials so that weighted mean baseline characteristics matched those in PCYC-1121. The following characteristics were identified as key prognostic factors and included in the base case propensity score model: number of prior lines of therapy, MZL subtype, response to prior therapy, and age. A sensitivity analysis was conducted including additional characteristics (B symptoms, time since last therapy, prior anti-CD20 therapy, bulky disease [>5cm], and lactate dehydrogenase above normal). Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% CIs. Results: After applying weights estimated from the base case propensity score model, the effective sample size (ESS) for ZANU was 68 (Table). Compared with IBRU, ZANU reduced the risk of progression (HR 0.38; 95% CI 0.21–0.69) and was associated with a higher ORR (OR 2.37; 95% CI: 1.13–4.96). OS was comparable for ZANU and IBRU, which is consistent with expectations for indolent lymphomas. The sensitivity analysis accounting for additional prognostic factors suggested the two treatments were comparable across all outcomes, owing in part to the low ESS (24) for ZANU associated with the expanded model. A leave-one-out analysis showed improved PFS (HR 0.33–0.45) for ZANU when excluding B symptoms, time since last therapy, or bulky disease from the expanded model. Conclusions: This MAIC demonstrated ORR and PFS benefits for ZANU vs IBRU in R/R MZL. [Table: see text]
CAR-T cells targeting CD38 and LMP1 and anti-tumor activity against NK/T cell lymphoma.
Authors: Li Hongwen , Shi Zhuangzhuang , Gao Yuyang , Li Zhaoming , Zhang Mingzhi
Published: June 2023

e19529

Background: Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis. In the past decade, chimeric antigen receptor transduced T (CAR-T) cell therapy has been a promising strategy against hematologic malignancies. Researchers have evaluated the efficacy of CAR-T cell targeting CD38 in multiple myeloma and NKTCL. LMP1 may induce a malignant transformation in B cells and epithelial cells, making it a non-negligible molecule in NKTCL. These suggest the potential clinical administration of CD38 and LMP1 targeting therapy. Methods: Four second-generation CAR-T cells including two single-targeted CAR (CD38-CAR and LMP1-CAR) and two tandem CAR (CD38-LMP1 Tan CAR 1 and Tan CAR 2) were constructed. Then the effects of four CAR-T cells on NKTCL cells were evaluated both in vitro and in vivo. Results: Four CAR-T cells could effectively eliminate malignant target-positive NKTCL cells in vitro. They could be activated and produce inflammatory cytokines in a target-dependent manner. Stimulated by CD38+LMP1+ NKTCL cells, two Tan CAR-T cells produced more IL-13, Granzyme B, IFN-γ and TNF-α than LMP1-CAR-T cells. In vivo test showed that CAR-T cells also exhibit significant anti-tumor effects in a xenotransplant NKTCL mice models. Two Tan CAR-T cells showed higher cytolytic activity against CD38+LMP1+ NKTCL cells than single-targeted CAR-T cells both in vitro and in vivo. Conclusions: We explored the feasibility of CAR-T cell therapy targeting both CD38 and LMP1 molecule. Our results indicated a promising effective therapeutic strategy for NKTCL.
Synergistic anti-tumor activity of the mTOR inhibitor everolimus and gemcitabine for the treatment of peripheral T cell lymphoma.
Authors: Huang Ling , Zhang Fen , Pang Diwen , Teng Yan , Jiang Xinmiao , Pan Lu , Sun Yichen , Guo Hanguo , Wei Xiaojuan , Chen Feili , Liu Sichu , Lin Caidi , Wang Yali , Wang Ning , Liang Zhanli , Huang Yilan , Ong Choon Kiat , Zhang Qingling , Tan Jing , Li Wenyu
Published: June 2023

e19538

Background: Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have dismal prognosis and limited treatment options. The mTOR inhibitor everolimus or gemcitabine as a single agent regimen had limited clinical efficacy in patients with R/R PTCL. Therefore, investigation of active combination therapies with everolimus for T cell lymphoma needs to be investigated. Methods: A retrospective analysis of 24 R/R PTCL patients were treated with everolimus and gemcitabine from December 2017 to March 2021. The primary endpoint was objective response rate (ORR). CellTiter Glo and AnnexinV FITC/PI were utilized to determine cell viability and apoptosis, respectively. Results: Here we demonstrated that combination treatment of everolimus and gemcitabine is effective in treating R/R PTCL patients, achieving an ORR of 70.8%, with 45.8% complete response rate. The median time to response was 1.7 months. With a median follow-up time of 22.3 months (95% confidence interval[CI], 5.7-39.0), the median PFS of all patients was 9.9 months (95%CI, 0-20.81), the median DOR was 16.8 months for responders. Patients with best response of CR and PR achieved superior PFS (18.7 vs. 1.2 months, P = 0.0007) and OS (30.9 vs. 5.8 months, P = 0.021) than that with SD and PD. Grade 3 or 4 neutropenia, thrombocytopenia and anaemia occurred in 13 (29.2% grade 3 and 25.0% grade 4), 11 (8.3% grade 3 and 37.5% grade 4) and 7 (16.6% grade 3 and 12.5% grade 4) patients, respectively. Functional in vitro studies showed that combination treatment synergistically inhibited cell viability and induced apoptosis in PTCL cell lines. Mechanistically, transcriptomic profiling indicated that the synergistic effect was induced through the abrogation of MYC pathway. Conclusions: Collectively, our study sheds light on synergistic antitumor effect of combinatorial therapy, providing a potential therapeutic strategy for patients with R/R PTCL.
Outcomes with bendamustine lymphodepletion prior to brexucabtagene autoleucel for mantle cell lymphoma.
Authors: Chong Elise A. , Gerson James N. , Nasta Sunita Dwivedy , Landsburg Daniel J , Barta Stefan K. , Svoboda Jakub , Weber Elizabeth , Chong Emeline R. , Schuster Stephen J.
Published: June 2023

e19540

Background: Brexucabtagene autoleucel (brexu-cel) is approved for relapsed/refractory mantle cell lymphoma (MCL). Cyclophosphamide/fludarabine for lymphodepletion (LD) is standard LD prior to brexu-cel. Due to a recent fludarabine shortage as well as institutional practice, we have utilized alternatives to fludarabine-based LD prior to brexu-cel, predominantly bendamustine. Bendamustine is an attractive option because it is included in the label for another anti-CD19 CAR T cell product. We report our institutional experience with bendamustine LD followed by brexu-cel. Methods: We retrospectively examined our institutional records for all patients with MCL who were treated with bendamustine LD followed by brexu-cel from 2020-2022. Progression-free survival (PFS) was analyzed with Kapalan-Meier survival analysis. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. Results: 16 patients received bendamustine followed by brexu-cel. Median age was 65 years (range: 54-76). Median number of prior therapies was 3 (range: 3-8). All patients (100%) had received a BTK inhibitor prior to brexu-cel. 14/16 (88%) received bridging therapy. 14/16 (88%) patients had CRS; 11/14 (79%) had grade 1-2 CRS and 3 (21%) had grade 3 or greater CRS. 5 (31%) patients had ICANS; 2 (40%) had grade 1-2 ICANS, and 3 (60%) had grade 3 or greater ICANS. 10 (63%) patients received tocilizumab, 8 (50%) received dexamethasone, and 3 (19%) received anakinra for management of CRS and/or ICANS. Best objective response rate (ORR) was 81% with 11 (69%) patients achieving CR. Median follow-up was 13.4 months. Estimated 6-month progression-free survival was 86% (95%CI: 54-96%) and 12-month progression-free survival was 63% (95%CI: 32-82). Conclusions: Bendamustine LD prior to brexu-cel for MCL is feasible, and, although these numbers are small, appears to have comparable outcomes to that reported in real world brexu-cel data (best ORR 90% with 82% CR rate, 6 month PFS estimate 69%, 12 month PFS estimate 59%; Y Wang et al. J Clin Oncol 2023) and ZUMA-2 outcomes (93% ORR with 67% CR rate, 12 month PFS estimate 61%; M Wang et al. NEJM 2020).
What differences in outcomes exist in Hispanic patients being treated for lymphoplasmacytic lymphoma and waldenstrom macroglobulinemia?
Authors: Huston-Cravens Jacob , Fierro Maria Elena , Liu Qianqian , Michalek Joel , Diaz Duque Adolfo Enrique
Published: June 2023

e19541

Background: Lymphoplasmacytic Lymphoma (LPL) and Waldenstrom Macroglobulinemia (WM) are both rare diseases with little known about their longterm outcomes in ethnic minorities. Overall, the 5- and 10-year survival of this disease has improved over the last 60 years (Blood, PMID: 24948623), but few studies have explored outcomes in Hispanic (HI) patients. We analyzed demographics, treatment patterns and outcomes in patients diagnosed with LPL and WM comparing HI and Non-Hispanics (NH) in the US. Methods: Data was analyzed on LPL and WM patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) analyzing patient characteristics, age-adjusted incidence rate, and survival rate among HI and NH patients. Results: HI were diagnosed at a younger median age on both LPL and WM cohorts compared to NH (p <0.001). There was a higher percentage of HI patients diagnosed with LPL and WM before the age of 60 compared to that of NH (p <0.001). Regarding race of patients with LPL, most of both HI and NH patients identified as whites (94% vs 86%), followed by blacks (2% vs 6%). Regarding stage, a majority of both HI (50%) and NH (60%) patients diagnosed with LPL were Stage IV. In terms of radiation, 7% of HI patients with LPL received it, compared to 4% of NH patients (p=0.027). On survival analysis for LPL patients, the survival probability at 2, 5 and 10 years (y) of HI vs NH were similar. There was not an OS difference favoring HI/NH (p=0.49). On survival analysis for WM patients, the survival probability at 2, 5 and 10 y of HI vs NH were similar. The median survival time for patients with WM was similar between HI and NH patients and there was not OS difference favoring HI vs NH (p=0.16). On multivariate analysis for LPL and WM, those diagnosed over the age of 80 had worse OS compared to those younger than 60 (95% CI; 4.8-8.1 and 2-3.4, respectively). No OS benefit when adjusting for stage was observed for either LPL or WM. Conclusions: In LPL and WM patients HI patients were diagnosed at younger ages compared to NH for both LPL and WM, and more likely to be diagnosed before the age of 60. The median survival rates were similar between HI and NH patients diagnosed with both LPL and WM. These findings may be confounded by earlier diagnosis in HI patients; however, further studies are needed exploring biological ethnic differences to explain early diagnosis in LPL and WM among HI.
COVID-19 infection in patients on anti-CD20 monoclonal antibodies: Changes in clinical outcomes and management over time.
Authors: Ali Mohammad , Abdullah Hafez M , Ahmed Mamoon , Chaudhry Hammad , Khan Dawlat , Khalil Fouad , Wachira David , Bleeker Jonathan
Published: June 2023

e19542

Background: As the COVID-19 pandemic progressed, survival of patients in the general population with COVID-19 improved over time. It is less clear based on current data whether patients on anti-CD20 therapy experienced similar improvement in outcomes over time. Methods: We performed a retrospective study of all patients aged ≥ 18 years diagnosed with COVID-19 while receiving anti-CD20 therapy for hematologic malignancy and/or rheumatologic indications at our center from January 2020-January 2022. Our primary endpoint was median overall survival (OS) and clinical outcomes stratified by date of diagnosis (“early cohort” = 03/01/20 to 12/31/20, “later cohort” = 01/01/21 to 10/15/21, and “latest cohort” = 10/16/21 to 01/16/22”). Secondary endpoints were to describe changes in the management of patients receiving anti-CD20 agents as the pandemic progressed and to assess independent predictors of OS in this population. Results: The median OS of 186 patients in the entire group was 13 months and the case fatality rate (CFR) was 23%. The CFR of admitted patients was 84%, whereas it was 16% for those who were not admitted. To examine trends over time, we compared 71 patients in the early cohort to 69 in the later cohort, and 42 patients in the latest cohort. The median OS of patients in the early cohort was 18 months (0.1-27) compared to 9 months (0-22) in the later cohort, and 8 months (0-20) in the latest cohort (P = 0.1884). The proportion of patients who received steroids was relatively consistent as the pandemic progressed with 45% in the early vs. 41% in the latest cohort. Fewer patients received remdesivir (31% for early cohort vs 21% for latest cohort) and convalescent plasma (13% for early cohort vs 2% for latest cohort) over time. The only baseline or treatment characteristics associated with adverse outcomes were receipt of steroids and anticoagulation, both of which were associated with an increased risk of death ((HR = 5.5, p = 0.002) and (HR = 2, p = 0.043 respectively)). Conclusions: Patients receiving monoclonal anti-CD20 antibody therapy had worse clinical outcomes than previously reported outcomes for the general population. OS did not significantly improve as the pandemic progressed; the phase of the pandemic with the shortest median OS was from 01/01/21 to 10/15/21 during the Delta SARS-COV-2 wave. Our data demonstrates an increased risk of death in patients on monoclonal anti-CD20 who experienced a COVID-19 infection and were treated with steroids, consistent with other reports.
Systematic review determining the characteristics of primary bone lymphoma.
Authors: Benkhadra Raed , Auster Michael , Nayfeh Tarek , Abbas Alzhraa S. , Alsibai Reem , Benkhadra Khalid , Datta Paromita , Kaur Supreet
Published: June 2023

e19543

Background: Primary Bone Lymphoma (PBL) is defined as a lymphoma originating in an osseous site with no systemic disease. It is rare, constituting around 1% of all lymphomas. Due to its rarity, ascertaining natural history and standard of care treatments are based primarily on small case series but there have been no systematic reviews, randomized control trials or meta-analysis to establish optimal treatment strategies. Methods: We searched MEDLINE, Embase, Scopus and other sources, from each database's inception to September 2022. Outcomes of interest included mortality and progression at different time points, as well as complete response and partial response. Meta-analysis was conducted using the random-effects model. Results: The number of studies matching our inquiry was 51 ranging from 1955 to 2019. Total patients studied were 5,847 of which 3,055 were male and the dominant histology was diffuse large B cell lymphoma with 3,816. Treatment primarily consisted of radiation therapy, chemotherapy, or a combination of the two. Overall mortality at 2, 5 and 10 years was 17%, 29% and 39% respectively. Complete response to initial treatment was noted in 73% of patients. Disease progression at 2 and 5 years was 26% and 29% respectively. Patients aged older than 60 years and multiple sites of disease in the skeleton (such as axial and spine etc.) had worse outcomes with RR 1.76 (P value 0.0027) and 1.133 (P value 0.0167) respectively. Additionally, patients who underwent chemotherapy with radiation vs radiation alone had improved outcomes with a relative risk of 0.38 (P value of 0.0001). Patients who underwent radiation treatment in addition to chemotherapy tended to have improved outcomes with a relative risk of 0.60 but this was not statistically significant with a P value of 0.068. Conclusions: We performed a systematic review to determine the characteristics and current treatment of PBL. The analysis demonstrates the rarity and heterogenicity of the disease. The current standard of care is for chemoradiation, but this is based primarily on old case studies. Our study confirms the utility of multimodal treatment with a tendency for improved outcomes. However, further prospective trials are needed to determine the necessity of multimodal treatment given this hypothesis generating study. [Table: see text]
Serum IL-6 levels following siltuximab administration in castleman disease.
Authors: Mango Natalie , Shyamsundar Saishravan , Sarmiento Bustamante Mateo , Lavery Criswell , Pierson Sheila K. , van Rhee Frits , Fajgenbaum David
Published: June 2023

e19545

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder. Though etiology is unknown, interleukin-6 (IL-6) is a driver in a portion of cases. Siltuximab is a monoclonal antibody that targets IL-6 and has been approved by the Food and Drug Administration to treat iMCD. Treatment guidelines for iMCD note that IL-6 directed therapy can result in spurious elevation of serum IL-6, based on anecdotal reports. This could lead physicians to erroneously infer treatment failure. Herein we investigate an international natural history registry of CD to evaluate whether IL-6 levels are increased following siltuximab. Methods: Data on peak IL-6 levels measured in patients before and after receiving siltuximab was available for 40 patients. C-reactive protein (CRP) levels measured near peak IL-6 values before and after siltuximab were also collected where available (n=32). Peak IL-6 values were standardized by the upper end of the reference range. Median values and interquartile ranges were calculated for pre- and post-siltuximab CRP and peak IL-6 values. Wilcoxon signed-rank tests were used for statistical comparison. Results: Our cohort consisted of 40 patients who had lymph node histopathology consistent with Castleman disease. An expert panel confirmed 16 iMCD, 5 POEMS-MCD, 1 regional CD, 3 unicentric CD, 11 other diagnoses, and 4 remain to be determined. Breakdown by gender was 50% male (n=20) and 50% female (n=20) with a mean age of 40.76 years. We analyzed peak standardized IL-6 levels before and after treatment with siltuximab. Prior to treatment with siltuximab, the median IL-6 level was 3.18, whereas after treatment with siltuximab, the median IL-6 level was elevated to 557 (p = 1.8 x 10-12). Given that CRP is a well-established biomarker of IL-6 activity, we investigated whether the increased IL-6 was a reflection of increased disease activity in these patients. Here, we found that median CRP before treatment was 59.7 mg/L, whereas after treatment, median CRP decreased to 4.95 mg/L (p = 0.0005) suggesting that IL-6 levels were rising despite reduced disease activity. IL-6 levels rose almost 200-fold while CRP reduced over 10-fold. Conclusions: Our results indicate that IL-6 levels significantly increase after patients receive siltuximab. Given that CRP is a biomarker of IL-6 activity, we infer that IL-6 is artificially elevated but not having a functional impact in the patient. Therefore, IL-6 levels should not be measured after siltuximab is given and they should not be used to guide treatment decisions. [Table: see text]
Outcomes of intravenous and subcutaneous cladribine administration in patients with hairy cell leukemia: A systematic review and meta-analysis.
Authors: Basit Jawad , Zaheer Zaofashan , Khan Muhammad Hammad , Fatima Maurish , Taj Sobaan , Akbar Usman Ali , Rehman Mohammad Ebad Ur , Saeed Sajeel , Vikash Sindhu , Ramesh Nithya , Shahab Asna , Shahid Muhammad , Komel Aqsa , Irshad Umer , Tabassum Shehroze , Naeem Aroma
Published: June 2023

e19546

Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Cladribine (2CdA) monotherapy is used as a first line treatment for HCL. 2CdA can be administered intravenously (IV) or subcutaneously (SC). The aim of our study is to compare the safety and efficacy of these two routes of administration of 2CdA as a first line treatment of HCL. Methods: We conducted a systematic literature search across multiple databases and Google up to February 2023. We included studies that reported outcomes for either intravenous (IV) or subcutaneous (SC) cladribine (2CdA) therapy, as well as those that directly compared the two routes. Our primary efficacy outcomes were overall response rate (ORR) and complete response rate (CRR), and our primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random effects model and conducted subgroup analysis for HCL type (classical vs classic and variant both). We calculated odds ratios (ORs) for studies involving a head-to-head comparison between the two routes and used the Higgins I2 statistic to assess heterogeneity. Results: We identified a total of 25 studies (15 trials, 10 cohorts) with a patient population of 2669. The median age of the patients was 53.5 years. The pooled ORR and CRR for IV and SC 2CdA therapy were 96%, 82%, 88% and 67% respectively. The incidence of neutropenia (82% vs 61%) and infections (13% vs 16%) was greater for SC 2CdA than IV 2CdA. Five studies provided a direct comparison between SC and IV routes but three were excluded from the analysis due to unavailability of desired outcomes. Studies involving a direct comparison between the 2 routes of administration showed that the odds of achieving CRR were 86.6% greater with IV than SC 2CdA but these results were not significant. The proportion of adverse events was comparable for IV and SC routes. Subgroup analysis for HCL type did not resolve heterogeneity for ORR and CRR. It did, however, result in greater ORR for classic (92%) and mixed (92%) HCL treated with SC 2CdA. Conclusions: Compared to SC 2CdA, IV 2CdA is safer and more effective as a first-line treatment of HCL. However, future high-power randomized control trials that directly compare IV and SC routes are needed to confirm this evidence. [Table: see text]
Evaluating the effectiveness and tolerability of chemotherapy in hairy cell leukemia: A comprehensive systematic review and meta-analysis.
Authors: Basit Jawad , Zaheer Zaofashan , Ahmed Aleena , Fatima Maurish , Akbar Usman Ali , Ramesh Nithya , Shahab Asna , Rehman Mohammad Ebad Ur , Shah Zunairah , Saeed Sajeel , Ahmad Mahboob , Aisha Azka
Published: June 2023

e19547

Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Many treatment options are available for HCL. Our study aims to elucidate the safety and efficacy of each intervention through the pooled proportion of response to treatment and adverse events. Methods: We conducted a literature search across PubMed, Embase, Cochrane, and Google Scholar from inception till February 2023. We included clinical trials and cohorts of patients with HCL receiving modern anticancer drugs (cladribine, rituximab, cladribine plus rituximab, BRAF inhibitors, anti-CD22 monoclonal antibodies, and ibrutinib). The primary efficacy outcomes were Objective Response Rate (ORR) and Complete Response Rate (CRR) and the primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random Effects Model, with subgroup analysis for HCL type and study design. Results: Our meta-analysis included 44 studies (28 trials and 16 cohorts) with 3976 patients with HCL. The median age was 56.7 years. The highest efficacy was seen in patients receiving combination therapy of cladribine and rituximab, with an ORR of 97% and CRR of 92%. Cladribine monotherapy showed an ORR of 95% and CRR of 79%, while rituximab monotherapy had an ORR of 62% and CRR of 31%. BRAF inhibitors, anti-CD22 monoclonal antibodies, and ibrutinib showed less efficacy, with ORRs of 92%,78% and 51% and CRRs of 41%, 49%, and 17% respectively. Subgroup analysis for study design and HCL type did not resolve heterogeneity. The ORR and CRR with 95% Confidence Intervals and AEs for each regimen are given in the table. Conclusions: Cladribine with rituximab is the most effective treatment for untreated and relapsed HCL patients, with neutropenia as the most common AE. Since we pooled the proportions for treatment-naïve and relapsed cases together due to inavailability of segregated data, the results should be used cautiously in clinical decision making and limit the derivation of consensus for treatment of newly diagnosed or relapsed HCL. [Table: see text]
Clinical characteristics, survival outcomes, and prognostic factors in subcutaneous panniculitis like T-cell lymphoma: National Cancer Database analysis (2004-2018).
Authors: Baidoun Firas , Sluzevich Jason , Tun Han W. , Alhaj Moustafa Muhamad
Published: June 2023

e19548

Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare lymphoma accounting for less than 1% of mature T-cell lymphomas. Its natural history is not understood due to lack of large studies with long-term followup and an optimal therapeutic approach is not well-defined. Methods: The National Cancer Database was queried for patients aged 18 years and older diagnosed with SPTCL between 2004 and 2018. We excluded patients who lost to follow-up. Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: 353 patients with SPTCL were included. 63% were females, 62% Caucasian, and 26% African American, 50% had early stage (I and II) and 32% had advanced stage (III and IV). 58.4% received chemotherapy, 38.2% did not receive chemotherapy and 3.4% had unknown chemotherapy status. The median age at diagnosis was 49 years (range 18-90). The median overall survival (mOS) for the whole cohort was not reached In early-stage (N = 178), 49.5% had chemotherapy with 39% receiving single-agent chemotherapy and 60% receiving multi-agent chemotherapy. 18.5% received radiation. In advanced-stage (N = 112), 75.9% received chemotherapy with 19% receiving single-agent chemotherapy and 81% receiving multi-agent chemotherapy. 9.8% received radiation There was no significant difference in the mOS between advanced-stage and early-stage (161.5 months vs not reached, P = 0.051) In early stage, there was no significant difference in the OS between chemotherapy and no chemotherapy (mOS was not reached in both groups, P = 0.324). The same trend was seen in the advanced stage (mOS was not reached in both groups, P = 0.851) Compared to Caucasian, African American patients were younger (median age 47 vs 54 years), but there was no significant difference in disease stage, receiving chemotherapy or radiation or other disease related characteristics (IPI score, B-symptoms, and HIV infection). African American patients had better OS (mOS was not reached, P = 0.003). This significant difference was seen in early stage (mOS was not reached, P = 0.003), but not in advanced stage (mOS 162 vs 122 months, P = 0.113) On multivariate analysis, age and Charlson-Deyo score ≥3 were associated with worse OS (HR 1.028 95% CI 1.005-1.052; P = 0.018 and HR 14.711 95% CI 2.316-93.449; P = 0.004, respectively), whereas disease stage and chemotherapy status did not affect the OS (HR 0.938 95% CI 0.545-1.617; P = 0.819, HR 1.271 95% CI 0.175-9.255; P = 0.813, and HR 0.922 95% CI 0.489-1.738; P = 0.802, respectively). Conclusions: Our study indicates that SPTCL is predominantly an indolent lymphoma associated with long-term survival irrespective of stage and chemotherapy. A conservative therapeutic approach appears to be more appropriate than intensive therapeutic approach in most patients. A risk stratification algorithm is needed to determine the therapeutic intensity.
Racial bias in multiple myeloma clinical trials: Racial minorities continue to miss out on treatment advances.
Authors: Jasaraj Ranjit , Gaire Suman , Proskuriakova Ekaterina , Jasaraj Ranjana , Keruakous Amany R.
Published: June 2023

e20009

Background: Adequate representation of participants based on race and ethnicity in a clinical trial helps ensure the results' generalizability. There is a disparity in the participation of minorities in oncology clinical trials despite higher incidence and disease burden in them. The incidence of Multiple Myeloma (MM) in AA (African American) is twice as compared to White, and they are twice as likely to die from MM compared to White. Methods: We queried ClinicalTrials.gov in February 2023 for all completed interventional trials with the published results for Multiple Myeloma in the US. Demographic data were collected from all the studies. If not available, the primary manuscript was searched using the trial number. We excluded the studies involving other malignancies and conducted outside of the USA. Trials on prevention, diagnostics, supportive care, and antibiotics were also excluded. Incidence data of Multiple myeloma was obtained from the SEER database for each ethnicity and race. Results: Out of 194 trials included in our study, 133 (68.56%) reported at least either race or ethnicity. Of these trials, 83 (42.78) reported race, 124 (63.91) reported ethnicity, and 77 (39.69) reported both race and ethnicity. 5.67% of the trial participants were reported as Hispanic race. White, AA, and Asian represented 79.82%, 11.36%, and 3.10% of the trial participants, respectively. The number of trials reporting race or ethnicity has increased when comparing the trials conducted between 2001-2011 and 2012-2022 (58.3% vs. 90.3%); OR 6.4; 95% CI 2.77-17.98; p<0.001. Participation of Asians increased (2% vs. 5.5%; p<0.0005), while there were slight changes among AA (11.7% vs. 10.6%, p=0.1475), Hispanic (5.4% vs. 6%; p=0.3863), and White (80.8% vs. 77.8%, p=0.208) between 2001-2011 and 2012-2022. Conclusions: Despite ongoing efforts to improve the diversity of minorities in oncology trials, they are still under-enrolled in multiple myeloma. More studies and interventions are needed to address this disparity. [Table: see text]
Efficacy and safety of elranatamab in patients with high-risk relapsed/refractory multiple myeloma (RRMM): A subgroup analysis from MagnetisMM-3.
Authors: Larson Sarah Marie , Bahlis Nizar J. , Maisel Christopher , Karlin Lionel , Varshavsky Yanovsky Asya , Leip Eric , Sullivan Sharon T. , Viqueira Andrea , Touzeau Cyrille
Published: June 2023

e20017

Background: Data from the ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in patients (pts) with RRMM and no prior BCMA-directed therapy (Cohort A). Results in high-risk subgroups are reported. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups analyzed were R-ISS stage (I/II/III ), cytogenetic abnormalities (standard/high risk [high-risk defined by the presence of t(4;14), t(14;16) or del(17p)]), extramedullary disease (EMD) at baseline (Y/N), bone marrow plasma cell involvement (BMPC) at baseline (<50%/≥50%), and penta-refractory disease (Y/N). Results include data up through ~12 months after last pt initial dose. Results: Median treatment durations and the proportions of pts receiving treatment at the data cut-off are reported in the Table. The most frequent cause of discontinuation was progressive disease which was higher for all high-risk subgroups than the corresponding lower risk subgroups. A clinical benefit, assessed by the objective response rate (ORR), was observed across subgroups (Table). A multivariable logistic regression analysis for ORR including baseline age, ECOG, sex, region, cytogenetic risk, presence of EMD, BMPC involvement, prior stem cell transplant, R-ISS stage, number of prior lines, type of myeloma, and penta-refractory disease showed presence of EMD at baseline and non-IgG myeloma (vs IgG) as predictive of lower ORR. Light chain-only myeloma (vs IgG) was predictive of higher ORR. Median duration of response (DOR) was not reached in subgroups by 12 months, DOR rate at 12 months is reported in the Table. Any grade TEAEs were reported in 100% of pts in the study. The incidence of grade 3/4 TEAEs was overall similar across subgroups (Table). Conclusions: Elranatamab is efficacious and has a manageable safety profile in pts with high-risk RRMM and no prior BCMA-directed therapy. Clinical trial information: NCT04649359 . [Table: see text]
Role of PETCT in multiple myeloma: A 3 year data analysis of tertiary care center.
Authors: Gupta Neha , Pendharkar Dinesh
Published: June 2023

e20030

Background: Bone involvement is one of the most common presentations of multiple myeloma, seen in about two-thirds of patients at the time of diagnosis. Therefore, imaging is an integral part of diagnosis for detection of lytic bone lesions and extra medullary disease. Evaluation of disease burden in both multiple myeloma and plasmacytoma as measured by PET/CT scan and response evaluation to induction therapy using PET based SUV changes is an important research topic. Methods: Single center prospective study done from 1st January,2020 to 30th June,2021 in Sarvodaya hospital and research center, Faridabad. All patients with multiple myeloma and solitary plasmacytoma coming to Sarvodaya hospital were eligible for the study. Total of 42 patients were enrolled into the study. PET-CT was done at baseline and post treatment as planned. Results: Out of 42 patients, 2 patients were diagnosed as solitary plasmacytoma and 40 patients were diagnosed as multiple myeloma. The median age of presentation was 64 years with male predominance (64.29%). PET-CT was done pre-treatment, On the basis of PET-CT findings it was seen that < 3 focal lesions were seen in 24(57.14%) patients and > 3 focal lesions were seen in 18(42.86%) of patients, based on SUV max, lesions with < 4.2 SUV max value were seen in 23(54.77%) patients and lesions with > 4.2 SUV max values were seen in 19(45.23%) patients. Presence of extra medullary disease was seen in 17(40.48%) of patients. 39(92.86%) patients were available for response analysis post treatment.3(7.14%) patients were expired during the study due to treatment complications and comorbidities. On the basis of PET-CT findings post treatment there was statistically significant response seen with p value of < 0.05 in the number of focal lesions, lesions with SUV max and burden of extra medullary disease. Evaluation of response when assessed radio logically by PET-CT scan, it was seen that Complete response was found in 22(56.40%) patients, VGPR was seen in 4(10.25%) patients, PR was found in 12(30.77%) patients and PD was seen in 1(2.58%) patient. But the results of co-relation of PET-CT findings with survival outcomes were not significant. Conclusions: PET-CT plays a significant role in diagnosis and response assessment. But there is still no uniform criteria for quantification and visualization of FDG avid lesions for patients with multiple myeloma.
Comparison of daratumumab-based regimens as second-line therapy in relapsed/refractory multiple myeloma.
Authors: Charalampous Charalampos , Goel Utkarsh , Kapoor Prashant , Binder Moritz , Buadi Francis , Dingli David , Dispenzieri Angela , Fonder Amie L. , Gertz Morie A. , Gonsalves Wilson I. , Hayman Suzanne R. , Hobbs Miriam A. , Hwa Yi Lisa , Kourelis Taxiarchis , Lacy Martha , Leung Nelson , Lin Yi , Warsame Rahma M. , Rajkumar S. Vincent , Kumar Shaji
Published: June 2023

e20032

Background: The introduction of anti-CD38 antibodies (daratumumab) in the treatment landscape of multiple myeloma (MM) has increased the progression-free survival (PFS) in recent years. Still, the ideal combination (Dara-IMiD vs. Dara-PI) of these drugs in patients with relapsed MM is unclear. Methods: We reviewed MM patients treated with daratumumab as second-line therapy at our institution from 2016 to 2022 to assess the outcomes with the different combination therapies. We used the Kaplan-Meier method to estimate PFS from the first relapse. Results: We identified 329 patients with a median age of 63.6 years (range: 27.1 – 90.4). Most of the patients received triplet induction therapy (95%) and upfront transplant (67%) as primary therapy. At the time of Dara initiation, 41% were refractory to IMiDs, 22% to PIs, 18% to both, and 18% to neither drug. Patients treated with Dara-IMiD had significantly better PFS than Dara-PI (28.7 months vs. 18.5 months, p < 0.01, respectively). In a subgroup analysis based on the FISH results, high-risk patients had similar PFS outcomes (24.3 vs. 10.2 months, p = NS, respectively), while standard-risk patients benefited significantly from the Dara-IMiD regimen (48.3 vs. 19.2 months, p < 0.01, respectively). Among patients treated with Dara-IMiD, those already refractory to IMiDs from the first line had significantly shorter PFS than those without IMiD resistance (14.9 vs. 43.3 months, p < 0.01, respectively). In addition, the lenalidomide-based combination resulted in significantly better PFS compared to pomalidomide in our cohort (40.5 vs. 19.2 months, p < 0.01, respectively). However, no difference was found in the IMiD refractory population (12.3 vs. 15.1 months, respectively). Finally, no significant differences were seen between Dara-IMiD and Dara-PI in patients only refractory to IMiDs (16.1 vs. 12.8 months, p = NS, respectively). Conclusions: While further studies are required to adjudicate the best combination, we conclude that Dara-IMiD might be more effective in patients with relapsed MM, especially for patients not refractory to IMiD at first line. [Table: see text]
Determinants of overall survival (OS) of elderly patients with multiple myeloma: A National Cancer Database (NCDB) analysis of years 2004-2017.
Authors: Chaulagain Chakra Pani , Saba Ludovic , Liang Hong , Dominguez Barbara , Fu Chieh Lin
Published: June 2023

e20035

Background: The survival of older adults with multiple myeloma (MM) continues to improve due to advancements in therapy but there is limited real-world data around the outcome of elderly (≥ 75 years old) MM patients. These patients are at risk due to comorbidities, frailty and potential for reduced tolerance to treatment. In this IRB approved retrospective analysis, the NCDB was used to evaluate the 30-day mortality and the determinants of overall survival (OS) of elderly MM patients who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 54,766 patients ≥ 75 years old diagnosed and treated for MM from 2004 to 2017. Multivariable cox regression analysis with backward elimination was utilized to identify the independent survival factors, using significance level of p < 0.05. Kaplan-Meier survival curves were produced, and SAS version 9.4 was used to analyze the data. Results: Overall median survival time was 23 months; while survival rates of 1, 3, and 5-year were 61.9%, 38.0%, and 23.6%, respectively. Multivariable cox regression analysis with backward elimination method revealed that there were 10 significant independent survival factors including age, sex, race, ethnicity, education level, Charlson-Deyo score, facility type, median income, year of diagnosis, and treatment-regimen. Male patients were more likely to die compared to female patients (HR = 1.08, p < 0.0001). Black patients were predicted to have less death events compared to White patients (HR = 0.90, p < 0.0001). In addition to that, patients of Hispanic ethnicity were more likely to die compared to non-Hispanic patients (HR = 1.16, p < 0.0001). Subjects who were treated in non-academic facilities were more likely to suffer death compared to the ones who received care in academic centers (HR = 1.15, p < 0.0001). Patients with median income < $38,000 (HR = 1.10, p < 0.0001), $38,000-$47,999 (HR = 1.06, p = 0.0011) and $48,000-$62,999 (HR = 1.04, p = 0.0031) were more likely to die compared to patients with higher median income ≥ $63,000. The hematopoietic stem cell transplantation utilization rate was 0.1%. The 30-day mortality rate was 8%. Detailed analysis will be presented. Conclusions: This large real-world analysis of elderly MM patients shows that White and Hispanic patients have inferior OS compared to Blacks and non-Hispanics. Patients with lower economic status and those treated at a non-academic facility also had inferior survival compared to those with higher income and with access to care at an academic facility. The 30-day mortality is strikingly high (8%) in the elderly. The unacceptably high mortality could be improved by facilitating access to high quality care and prompt use of novel agents. Prospective studies are needed to identify and address determinants of disparity in MM care in elderly patients.
Socioeconomic factors associated with a late-stage multiple myeloma diagnosis: An analysis of the National Cancer Database.
Authors: Patel Chirag , Townley Liam P. , Silberstein Peter T. , Gallegos Jillian Marie
Published: June 2023

e20036

Background: Multiple myeloma is an aggressive monoclonal plasma cell proliferative disorder that is the second most common hematologic malignancy. On a global scale, multiple myeloma led to an estimated 106,000 deaths in 2018 alone. The exact cause of multiple myeloma is not well understood. Later stage of diagnosis is correlated with worse outcomes; thus, it is critical to assess the socioeconomic factors associated with diagnosis at early versus late stages. Methods: Using the National Cancer Database, we aimed to identify associations between socioeconomic factors of patients that present with Revised International Staging System (R-ISS) stage I multiple myeloma in comparison to R-ISS stage III at diagnosis. In this study, 5,512 patients from the National Cancer Database who were diagnosed with R-ISS stage I and stage III multiple myeloma were analyzed based on age, ethnicity, race, education, insurance type, income, education, geographic location, facility type, sex, Charlson-Deyo score, and urban or rural setting. Demographic factors of patients that presented with stage I and stage III disease were analyzed using chi square, ANOVA, and multivariate analyses. All patients included in the study were diagnosed with multiple myeloma between 2004 and 2020. Results: We identified significant (P < 0.05) associations between insurance type, median income, education, rural setting, and Charlson-Deyo score with diagnosis of R-ISS stage III multiple myeloma. For insurance type, private insurance, other government insurance, and Medicaid had lower percentages of R-ISS stage III diagnosis than patients without insurance (P < 0.001). Medicaid and over government insurance were up to 70% less likely to present with stage III MM than patients without insurance (P < 0.001). Regarding income and education, patients from a zip-code associated with an income of < $38,000 and zip-codes with lower levels of high school diploma had higher rates of stage III multiple myeloma diagnosis (P < 0.001). Patients from completely rural or less than 2,500 urban population adjacent to a metro area (P < 0.005) and not adjacent to a metro area (P < 0.025) showed significant increase in later stage multiple myeloma diagnosis than those from a metro setting with population above one million. Patients with Stage III at presentation were older than patients with stage I on average (P < 0.001). There were no significant differences seen based on race, sex, ethnicity, or region in the United States. Conclusions: Factors associated with increased likelihood of later stages of diagnosis of multiple myeloma include insurance type, median income, education, and rural location. Future analysis should further investigate the specific barriers to early patient diagnosis and treatment due to insurance type, education level, and rural setting.
Clinical validation of next-generation sequencing-based clonality assays for minimal residual disease tracking in multiple myeloma.
Authors: Lin Chuanming , Jian Qijie , Huang Zoufang , Xie Shuiling , Xin Liuyan , Wu Haiyan , Pang Fei , Liao Changfeng , Chen Yijian
Published: June 2023

e20037

Background: The prognosis of multiple myeloma (MM) patients is dependent on minimal residual disease (MRD) status after treatment. Multicolor flow cytometry (MFC) as a clinical MRD evaluation method has certain limitations regarding sample requirement, sensitivity and specificity. Next-generation sequencing (NGS)-based B cell receptor (BCR) clonality assessment has an edge in lymphoid clone MRD detection, with easier sample preparation and higher sensitivity. NGS-based BCR clonality assays were performed to evaluate curative effect and track MRD of MM patients, and its performance in testing samples with limited DNA contents was explored. Methods: In this retrospective study, newly diagnosed or relapsed MM patients with paired sample collected before and after initial treatment were included, and OriMIRACLE L NGS assay were used for BCR clonality detection in genomic DNA (gDNA) extracted from clinical residual marrow smear samples. The quantitative accuracy of NGS was compared to MFC. The concordance of MRD between MFC, NGS and clinical response assessment were analyzed. Results: From December 2016 to April 2022, 29 patients were included with a median age of 65 years old. The gDNA input of the sample collected before treatment was 100.0 ng, and the median DNA content of the sample collected after treatment was 1673.4 ±594.8 ng. The quantitative results of NGS and MFC were consistent in samples with a frequency of cancer cells of above 1x10-4 among all nucleated cells. BCR clonality detection in 23 newly diagnosed and 6 relapsed cases showed a 100% sensitivity at diagnosis. For post-treatment monitoring, patients with positive MRD by both MFC and NGS (n = 18), the MRD results were consistent with clinical response assessment. One of the patients achieved complete response (CR), while the remaining patients were unable to achieved CR. The CR patient was relapsed after 134 days. The clinical responses of 11 cases with negative MRD by MFC and positive MRD by NGS were reviewed. There were 7 cases with CR, 3 cases with very good partial response or partial response, and one case with stable disease. Among those CR patients, except for one patient who was lost to follow-up, 4 patients who underwent continuous treatment were still CR and 2 patients who had treatment discontinued recurred at 67 and 134 days. Conclusions: OriMIRACLE L NGS assay showed the higher sensitivity and specificity of MRD evaluation than MFC. For patients with negative MRD by MFS and positive MRD by NGS, recurrence might occur in case of treatment discontinuation. It is recommended to consider carefully that whether maintenance treatment is required in such cases.