tbuckley/cabot-search huggingface dataset:
Patient-reported treatment-related symptoms and use of the PRO-CTCAE for multiple myeloma clinical trials: A qualitative interview study.
Authors: Kelly Kato, Rikki Mangrum, Heather Gerould, Karolina Schantz, Alexandra Bryant, Eva Katz, Katharine Gries
Journal: Journal of Clinical Oncology (2024)

e19516 Background: Therapeutic regimens for multiple myeloma (MM) involve multiple pharmacological agents, including steroids. Many cause treatment-related symptoms that add to patient burden or may trigger treatment cessation. This study gathered qualitative data about the patient experience with MM treatments, including regimens with steroids. Findings were summarized and compared to the Patient Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), to assess its comprehensiveness and relevance in MM clinical trials. Methods: Individual, semi-structured interviews were conducted virtually with a diverse sample of 16 US-based, English-speaking adults (38% male, 25% Black, 13% Hispanic) to explore their experiences with MM and treatments, including perspectives on steroids and potential benefits of steroid-sparing regimens. Content analysis was used to summarize and compare terminology participants used to describe their experiences with treatments. Results: Participants reported a diverse set of treatment-related symptoms impacting their overall experience, indicating the importance of assessing regimen tolerability in clinical trials. Steroids were linked to increased energy that interfered with sleep or functioning, irritability, taste changes, weight gain, increased appetite, and cognitive symptoms like brain fog. Participants reported that most symptoms were tolerable, but they would prefer to avoid steroids if treatment benefits did not diminish. Many reported symptoms were included in the PRO-CTCAE items (see Table), but several symptoms related to regimens with steroids are not covered: excess energy, bitter/metallic taste, taste sensitivity, brittle nails, irritability, hunger/increased appetite, and muscle weakness. Conclusions: MM patients experience a range of treatment-related symptoms, many of which impact their quality of life. If given the option, patients would prefer a steroid-free regimen if there was proven clinical benefit. While the PRO-CTCAE covers most of the treatment-related symptoms, proving to be an option for multiple myeloma clinical trials, additional PRO instruments may be needed to cover specific gaps in the PRO-CTCAE item library content coverage. [Table: see text]
Real-world schedule de-escalation of teclistamab in patients with relapsed/refractory multiple myeloma.
Authors: Carlyn Rose Co Tan, Andriy Derkach, Kylee Maclachlan, Malin Hultcrantz, Hani Hassoun, Sham Mailankody, Urvi A Shah, Sridevi Rajeeve, Gunjan L. Shah, Michael Scordo, David J. Chung, Heather Jolie Landau, Sergio Giralt, Alexander M. Lesokhin, Neha Korde, Dee Lin, Bingcao Wu, Jessica Fowler, Mariana Fernandez, Saad Zafar Usmani
Journal: Journal of Clinical Oncology (2024)

7536 Background: Teclistamab (Tec) is the first BCMAxCD3 bispecific antibody approved for triple-class-exposed relapsed/refractory multiple myeloma (RRMM). The MajesTEC-1 study demonstrated an overall response rate (ORR) of 63% and a median progression-free survival (mPFS) of 11.3 months (mos). Herein, we examined real-world pt characteristics and outcomes associated with Tec in (1) pts treated within the first 4 mos of Tec approval (early initiators who were expected to have high disease burden) as compared to recent initiators, and (2) any pts who switched to de-escalated dosing schedules. Methods: This is a retrospective study of pts with RRMM treated with Tec at Memorial Sloan Kettering Cancer Center from 11/29/22 to 11/30/23 (analysis cut-off: 12/31/23). Responses were evaluated per IMWG Response Criteria. Pt characteristics were summarized by frequency (%) or median (interquartile range [IQR]). PFS was evaluated using the Kaplan-Meier method. Results: In 77 pts who received ≥1 Tec dose, the median age was 70 (IQR 63-77); 55% male; 14% Black; and 42% had high-risk cytogenetic abnormalities (HRCA). The ORR was 62% for 69 response-evaluable pts, including 42% with ≥very good partial response (VGPR). The median time to first response was 1.9 mos (IQR 1.0-2.4). After a median follow-up (mFU) of 7.6 mos, 6-mo PFS rate was 52.3% (95%CI 41.5-66%). The median duration of response has not been reached. In the cohort of early initiators (n=34), pts had more prior lines of therapy (LOT; median 8 vs 5, P=0.002) and higher proportion of prior BCMA therapy use (62% vs 23%; P=0.002) as compared to recent initiators treated after 3/31/23 (n=43). ORR was 67% and 59%, respectively (P=0.80; Table). Among all pts at data cut-off, 25 (32%) switched from weekly to every-other-week or monthly Tec after a median time of 3.1 mos from Tec initiation (95%CI 1.8-4.6) and based on achieving ≥PR and/or toxicity. At mFU of 5.3 mos since switching, 6-mo PFS rate was 94.1% (95%CI 83.6-100%). Conclusions: In this real-world study, Tec demonstrated comparable ORR to MajesTEC-1. Both early and recent Tec initiators had high baseline risk features. A higher proportion of early initiators had prior BCMA therapy and more LOTs, but both cohorts yielded consistently high treatment response rates. In pts who responded, schedule de-escalation was feasible with a high subsequent 6-mo PFS. Updated multicenter findings will be presented at the meeting. [Table: see text]
Health-related quality of life (HRQoL), functioning, and symptoms with odronextamab monotherapy in patients (pts) with relapsed or refractory follicular lymphoma (R/R FL) by POD24 status in the ELM-2 study.
Authors: Jose Caetano Villasboas, Laura Magnano Mayer, Benoît Tessoulin, Seok-Goo Cho, Michal Taszner, Silvana Novelli, Stefano Luminari, Michele Merli, Ana Jiménez Ubieto, Michelle Poon, David Tucker, Jan Andrzej Walewski, Cristina Ivanescu, Aafia Chaudhry, Hesham Mohamed, Srikanth R. Ambati, James Harnett, Siddhesh Kamat, Tae Min Kim
Journal: Journal of Clinical Oncology (2024)

e19057 Background: In ELM-2 (NCT03888105), a Ph 2, single arm, open label trial, odronextamab demonstrated robust efficacy, generally manageable safety, and overall maintenance of patient-reported outcomes (PROs) in R/R FL pts (Villasboas et al. ASH 2023). In FL, pts with disease progression within 2 yrs of frontline chemoimmunotherapy (POD24) are hard to treat with poor clinical outcomes, representing an unmet need. We report PROs by POD24 status in pts with Grade 1–3a R/R FL from ELM-2. Methods: Pts received IV odronextamab in 21-day cycles (C): 80 mg QW in C1–4, with C1 dose step up to mitigate cytokine release syndrome, then 160 mg Q2W (Q4W if complete response ≥9 mo) until progression. PROs were collected at baseline (BL), Wks 2–4, 10, then Q8W in Yr 1, and Q12W in Yr 2. Post-hoc POD24 subgroup analyses were performed on six EORTC QLQ-C30 scales, the EQ-5D-3L VAS, and FACT-Lym LymS. Estimated mean change from BL (CFB) was analyzed using mixed models for repeated measures (MMRM) through Wk 42 (≥10 pts at last assessment). Published meaningful CFB thresholds were used to define deterioration/improvement in responder analyses. Results: By Jan 31, 2023, 140 pts with R/R FL had received odronextamab. Pts with POD24 (n=70) were younger than pts without POD24 (n=70; median age 57.5 vs 62.0 y), had fewer prior Tx lines (median 2 vs 3), and a higher proportion double refractory to anti-CD20 Ab + alkylator (53% vs 29%). Objective response rate was similar in evaluable pts with (n=63; 79%) and without (n=65; 80%) POD24. PRO questionnaire completion ranged from 52–95% through Wk 42 across groups. Descriptive analyses suggest BL PRO scores were similar by POD24 status, showing good HRQoL/functioning and low symptom burden, and were generally maintained through Wk 42 with minimal between-group differences (overlapping 95% CIs for LS mean CFB [Table]). In both groups, more pts reported PRO maintenance or improvement vs deterioration across visits, except for fatigue at Wk 10 in pts without POD24. Conclusions: In pts with heavily pretreated R/R FL, odronextamab Tx maintained HRQoL, functioning, and symptoms irrespective of POD24 status. Clinical trial information: NCT03888105 . [Table: see text]
Effect of 1-L-MT on immunotherapy of diffuse large B-cell lymphoma via downregulation of PD-L1.
Authors: Sun Chengtao, Xue Xu, Chunping Yao
Journal: Journal of Clinical Oncology (2024)

e19066 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, accounting for more than 30% of all cases. Although with the development of treatment, the 5 years overall survival rates remain low, range from 30%-50% for all DLBCL patients. In addition to R-CHOP, immunotherapy has attracted much attention. However, the single-agent activity of most immune checkpoint inhibitors (ICI) in DLBCL has been overwhelmingly disappointing. It is urgent to develop new methods to enhance the efficacy of DLBCL treatment. Our previous study demonstrated that 1-L-MT, an IDO1 inhibitor, can inhibit tumor growth of DLBCL. Here, we investigate whether 1-L-MT promotes antitumor immunity of ICI in DLBCL. Methods: The role of 1-L-MT on cell proliferation in vitro and tumor growth in NOD/SCID mice were investigated. RNA-seq analysis was performed in 1-L-MT treated and control OCI-Ly10 cells. ChIP assay was performed using AhR-precipitated DNA samples of OCI-Ly10 cells (treated with or without 1-L-MT) and primers for PD-L1, and he expression of PD-L1 was evaluated by RT-qPCR. The combination of 1-L-MT and PD-1 blockade therapy were performed in C57BL/6 mouse bearing tumor cells to evaluate the antitumor activity. Results: In our study, IDO1 inhibitor 1-L-MT sensitized diffuse large B cell lymphoma to immunotherapy via downregulation of PD-L1. Further study confirmed that 1-L-MT could reduce the expression of PD-L1 and upregulate the expression of MHC-I antigen presentation factors. In addition, RNA-seq and bioinformatics analysis revealed that the transcription factor AhR may involved in the downregulation of PD-L1 transcription level induced by 1-L-MT. Mechanistically, ChIP and RT-qPCR assays were conducted to test AhR-PD-L1 interaction, and the results showed that AhR directly bound the promoter of PD-L1. 1-L-MT-mediated PD-L1 reduction promoted T cell activation and T cell killing of tumor cells. The combination of 1-L-MT and anti PD-1 antibody significantly inhibited DLBCL growth and extends the lifespan of tumor-bearing mice. Conclusions: Our study unveiled a mechanism by which 1-L-MT induces PD-L1 downregulation via AhR and provides methods to facilitate immunotherapy in diffuse large B-cell lymphoma. The present study may provide a theoretical foundation for overcoming the challenge of low-sensitivity to immunotherapy in DLBCL.
An institutional experience of a rare diagnosis of subcutaneous panniculitis-like T-cell lymphoma.
Authors: Callie Fort, Rohit Raina, Rakesh Surapaneni
Journal: Journal of Clinical Oncology (2024)

e19073 Background: Subcutaneous Panniculitis-like T-cell lymphoma (SPTCL) is a rare diagnosis making up &lt; 1% of Non-Hodgkin lymphomas. Data from Surveillance Epidemiology and End Results (SEER) identified a total of 204 cases from 2000-2020. Clinically, SPTCL presents as subcutaneous nodules and is difficult to distinguish from other more common conditions such as lupus erythematosus panniculitis. Most of our understanding on presentation, diagnosis and treatment on SPTCL is limited to small case series. Methods: Following IRB approval, a multi-center retrospective clinical and pathological review identified patients diagnosed with SPTCL from 1/1/2013-10/24/23. The study was conducted at Baylor Scott &amp; White system (CTX). Inclusion criteria included ≥ 18 years old, SPTCL AB sub-type. Patients were seen for &gt; 2 visits during time of active treatment. Cases of SPTCL y8 sub-type were excluded from the study. A descriptive analysis of the clinical presentation, treatment choice/duration, and clinical outcomes was generated. Results: A total of 5 patients met criteria for inclusion during the previously defined time period. The median age at diagnosis was 39 with a median follow up of 6 years. Patients presented with multiple nodular lesions affecting the chest, trunk, axilla, arms, and legs. Sixty percent of patients received misdiagnosis and experienced delay in appropriate treatment with a maximum delay of 10 years. Histopathology showed panniculitis-like lymphoid infiltrate composed predominantly of T lymphocytes, with areas of adipocyte rimming and a background of fat necrosis. No patients developed hemophagocytic syndrome. Patients were treated with steroids alone or in combination with cyclosporine, methotrexate, and/or romdespin. Sixty percent of patients achieved a complete response, and 40% remain in remission. The 5-year disease specific survival rate was 100%. Conclusions: SPTCL showed an indolent course in the patient population studied. All patients treated with systemic steroids as first line therapy responded favorably. When tolerated cyclosporine and methotrexate controlled disease in patients that showed progression following the completion of steroid taper.
Quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma (TENDMM): A systematic review and meta-analysis.
Authors: Aneeta Channar, Syed Arsalan Ahmed Naqvi, Muhammad Ali Khan, Arifa Bibi, Akshat Saxena, Nikita Tripathi, Ahmad Iftikhar, Ammad Raina, Kaneez Zahra Rubab Khakwani, Irbaz Bin Riaz, Muhammad Husnain
Journal: Journal of Clinical Oncology (2024)

e19534 Background: Immunomodulatory drugs, proteasome inhibitors plus dexamethasone are the standard triplet induction regimen for TENDMM. We analyzed the efficacy of adding either anti-CD38 monoclonal antibodies (mAbs) or anti-SLAMF7 antibody to the triplet therapy. Methods: Ovid MEDLINE, EMBASE and published abstracts were systematically searched from each database’s inception through 01-31-2024 to identify II/III trials assessing quadruplet therapy versus triplet therapy in TENDMM patients. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratios (OR) for overall response rates (ORR), measurable residual disease (MRD) negativity rate (with sensitivity of 10 - 5 ) and grade 3 or higher treatment-related adverse events (G≥3 TRAE) were summarized using random effects meta-analysis via inverse variance approach. Additional subgroup analyses based on the cytogenetic risk were performed. P-value of interaction (Pint ) &lt; 0.1 was pre-specified as statistically significant for the difference between the two groups. Results: 3806 studies were screened and seven trials were included with a total of 3546 patients. Four trials (2303 patients) assessed the addition of anti-CD-38 mAbs and three (1243 patients) assessed anti-SLAMF7 mAb, elotuzumab to the triplet regimen. Quadruplet therapy significantly improved PFS as compared to triplet (HR: 0.63; 95% CI: 0.43-0.92), and the PFS benefit was also observed in standard risk group (HR 0.5; 95% CI 0.2-0.9); however, results were insignificant for high-risk group (HR 0.8; 95% CI 0.62-1.93). No significant OS benefit was observed (HR: 0.79; 95% CI 0.49–1.26); however, data for three trials (CASSIOPEIA, DSMM XVII, PERSEUS) is immature, with longer-term follow-up ongoing. Quadruplet therapy showed significant results for very good partial response or better (OR: 1.7; 95% CI 1.2-2.36), stringent complete response (OR: 1.74; 95% CI 1.27-2.07) and complete response or better (OR: 1.91; 95% CI 1.19-3.06). MRD rate shows benefit with quadruplet therapy (OR: 2.59; 95% CI 2.22-3.01). Improved MRD rate was also observed for high-risk (OR 2.13; 95% CI 1.4-3.2) and standard-risk group (OR 2.58; 95% CI 1.68-3.94). Secondary analysis for efficacy of anti-CD38 mAbs showed benefit for PFS (HR: 0.44; 95% CI: 0.35-0.56), ORR (OR: 1.77;95% CI: 1.02-3.06), and MRD (OR: 2.98; 95% CI 1.8-4.8). G ≥3 TRAE did not significantly differ between the groups (OR: 1.05; 95% CI 0.97-1.12). However, quadruplet therapy showed significant risk of infection (OR: 1.2; 95% 1.05-1.35) and thrombocytopenia (OR: 1.41; 95% CI 1.24-1.59). Conclusions: Quadruplet therapy improved PFS, ORR, and MRD rates compared to triplet regimen and has demonstrated promising benefits to be considered the new standard of care for TENDMM patients.
Comparative effectiveness of linvoseltamab versus standard-of-care (SOC) treatment (tx) in real-world patients (pts) in the United States (US) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM).
Authors: Shaji Kumar, Katja C Weisel, Qiufei Ma, Christian Hampp, Olivier Humblet, Mostafa Shokoohi, Nicolle Bonar, Paul Spin, James Harnett, Wenzhen Ge, Jessica J Jalbert, Rachel E Sobel, Glenn Scott Kroog, Karen Rodriguez-Lorenc, Sundar Jagannath
Journal: Journal of Clinical Oncology (2024)

7561 Background: Pts with TCE RRMM have poor outcomes and a high unmet need, with no established SOC tx. LINKER-MM1 (NCT03761108) is a single-arm, Phase 1/2 study investigating linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody, in pts with RRMM who were previously treated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody, or were triple-class refractory (TCR) to these tx. The aim of this study was to contextualize LINKER-MM1 by comparing outcomes with linvoseltamab vs a real-world (RW) external control arm (ECA). Methods: A RW ECA was derived from 2 US electronic health record databases (COTA, Guardian Research Network) of pts who started a new line of therapy (LOT) after classification as TCE or TCR and met key eligibility criteria for LINKER-MM1. Eligibility was assessed at the initiation of each new LOT, and all eligible LOTs were included in the ECA. Data in Phase 2 pts who received linvoseltamab 200 mg in LINKER-MM1 were included (data cutoff: Sep 8, 2023). Inverse probability of tx weighting (IPTW) was used to reduce imbalances between the RW and LINKER-MM1 cohorts. Key prognostic factors were identified using a systematic review and rank ordered by an international committee of MM experts (Kumar et al., 2023). Outcomes included overall response rate (ORR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). An independent committee of epidemiology and oncology experts reviewed the comparability of the cohorts and endpoint assessments prior to conducting comparative analyses. Results: Comparative analyses were performed in 105 pts in the linvoseltamab cohort and 101 RW pts (137 LOTs). Following IPTW, the distribution of cytogenetic risk, age, TCR status, Eastern Cooperative Oncology Group Performance Status, and platelet count were balanced between the 2 cohorts (absolute standardized mean difference &lt;0.10). After adjustment, pts receiving linvoseltamab had significantly improved ORR, PFS, TTNT, and OS vs the RW ECA (see table). Conclusions: Linvoseltamab significantly improved outcomes vs RW SOC in the US, highlighting its potential as a highly effective tx in pts with TCE RRMM. [Table: see text]
Impact of renal impairment (RI) on pharmacokinetics (PK) and clinical outcomes with mezigdomide plus dexamethasone (DEX) in relapsed/refractory multiple myeloma (RRMM).
Authors: Suzanne Trudel, Nizar J. Bahlis, Rakesh Popat, Maria-Victoria Mateos, Annette J. Vangsted, Karthik Ramasamy, Joaquín Martínez-Lopez, Hang Quach, Robert Z Orlowski, Joseph Burnett, Allison Gaudy, Wencong Chen, Jing Gong, Joseph T. Hadala, Cynthia Donahue, Phillip Koo, Yue Zhu, Jessica Katz, Paul G. Richardson
Journal: Journal of Clinical Oncology (2024)

7539 Background: RI is a common complication in MM and may alter drug elimination, leading to increased systemic exposures, risk of adverse events (AEs), and dosing adjustments. The novel CELMoD agent mezigdomide (MEZI) is being investigated alone or with DEX in the CC-92480-MM-001 (NCT03374085) phase 1/2 trial. MEZI has shown dose-dependent linear PK with rapid absorption and is mainly eliminated through hepatic metabolism, with renal elimination playing a smaller role. Here we investigate the impact of RI on the efficacy, safety, and PK of MEZI + DEX in RRMM. Methods: Eligible patients (pts) had RRMM, ≥ 3 prior lines of therapy, triple-class refractoriness, and disease progression ≤ 60 days of last therapy. Pts were stratified by creatinine clearance (CrCl), excluding those with CrCl &lt; 45 mL/min or needing dialysis. Oral MEZI (1 mg) was given on days 1–21 per 28-day cycle + weekly DEX. MEZI doses were not adjusted based on RI. Responses, AEs, and PK were assessed descriptively over the full population and in pts with no RI (CrCl ≥ 90 mL/min), mild RI (CrCl 60–&lt; 90 mL/min), and moderate RI (CrCl 30–&lt; 60 mL/min) at baseline. MEZI clearance and PK exposure were estimated from an integrated population PK model. PK exposure parameters were stratified by chronic kidney disease (CKD) staging. Results: 101 pts received MEZI + DEX in the dose-expansion cohort; 37 had no RI, 41 had mild RI, and 23 had moderate RI. Grade (Gr) 3/4 treatment-emergent AEs (TEAEs) were similar, occurring in 91.1% (overall), 89.2% (no RI), 90.2% (mild RI), and 95.7% (moderate RI) of pts. TEAEs were mostly hematologic, with neutropenia the most common Gr 3/4 TEAE; its occurrence did not differ in no RI (75.7%), mild RI (75.6%), and moderate RI (73.9%) cohorts. Non-hematologic Gr 3/4 TEAEs were low. Eighty-nine (88.1%) and 32 (31.7%) pts had MEZI dose interruptions and reductions, respectively. Overall response rate (ORR) was 40.6% in all pts, 56.8% in no-RI pts, 29.3% in mild-RI pts, and 34.8% in moderate-RI pts (Table). Evaluated as a continuous variable, CrCl showed no apparent relationship with MEZI oral clearance or systemic exposures. This was supported by subgroup evaluation of MEZI exposures by CKD stage. Results showed MEZI exposures in mild or moderate RI are consistent with no RI. Conclusions: Based on renal function, there was no adverse trend between efficacy, safety, and PK of MEZI + DEX. MEZI dose modifications are likely not required for pts with mild to moderate RI. Clinical trial information: NCT03374085 . [Table: see text]