bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Düll Johannes , Maddocks Kami J. , Gonzalez-Barca Eva , Jurczak Wojciech , Liberati Anna Marina , Obr Aleš , Gaidano Gianluca , Abrisqueta Pau , André Marc , Dreyling Martin H. , Menne Tobias , Dirnberger-Hertweck Maren , Weirather Johannes , Ambarkhane Sumeet Vijay , Salles Gilles A. 
Published: June 2021

7513 Background: L-MIND (NCT02399085) is an ongoing, open-label, Phase II study of tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, plus LEN in ASCT-ineligible patients (pts) with R/R DLBCL. Primary analyses and 2-year efficacy results were previously presented; we report an updated efficacy analysis with ≥35 months follow up (cut-off: October 30, 2020). Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, had 1–3 prior systemic therapies (Tx), including ≥1 CD20-targeting regimen, with an ECOG status of 0–2. Pts received 28-day cycles (C) of tafasitamab (12 mg/kg IV), once weekly during C1–3, with a loading dose on Day 4 of C1, then every 2 weeks (Q2W) during C4–12. LEN (25 mg PO) was administered on Days 1–21 of C1–12. After C12, progression-free pts received tafasitamab Q2W until disease progression. The primary endpoint was objective response rate (ORR), assessed by IRC. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Results: Eighty of 81 enrolled pts received tafasitamab + LEN and were included in the full analysis set (1 prior Tx, n=40; 2+ prior Tx, n=40). At data cut-off, the overall ORR was 57.5% (n=46/80), including complete response (CR) in 40% of pts (n=32/80) and partial response (PR) in 17.5% of pts (n=14/80) (Table). Kaplan-Meier estimates: median DoR=43.9 months (95% CI: 26.1–not reached [NR]), and NR in pts who achieved a CR (95% CI: 43.9–NR); median PFS=11.6 months (95% CI: 6.3–45.7), with median follow-up 33.9 months; median OS=33.5 months (95% CI: 18.3–NR), with median follow-up 42.7 months. There were no unexpected toxicities or new safety signals. Conclusions: Combination Tx with tafasitamab + LEN followed by tafasitamab monotherapy provided durable responses in pts with R/R DLBCL not eligible for ASCT, with a manageable safety profile. These long-term data indicate the potential of tafasitamab + LEN followed by extended tafasitamab monotherapy in achieving prolonged remission and survival benefit in this patient population, especially at first relapse. Clinical trial information: NCT02399085. [Table: see text]
Comparative efficacy of tisagenlecleucel (tisa-cel) and lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL).
Authors: Schuster Stephen J. , Zhang Jie , Yang Hongbo , Agarwal Abhijit , Tang Wenxi , Martinez-Prieto Marcela , Bollu Vamsi , Ma Qiufei , Kuzan David , Maziarz Richard T. , Kersten Marie José 
Published: June 2021

7535 Background: Chimeric antigen receptor T-cell therapies tisa-cel and liso-cel are effective treatments for r/r DLBCL (Schuster 2019, Abramson 2020). This study compared efficacy outcomes of tisa-cel and liso-cel in r/r DLBCL using matching-adjusted indirect comparison (MAIC). Methods: Individual patient-level data (IPD) from JULIET (tisa-cel; NCT02445248; 02/2020 datacut) were weighted to match the patient population in TRANSCEND (liso-cel; NCT02631044; 08/2019 datacut). Baseline prognostic factors available in both trials were adjusted for age, sex, histology, ECOG performance status [ECOG PS], left ventricular ejection fraction, radiologic sum of product diameters, lactate dehydrogenase, prior stem cell transplantation [SCT], use of bridging therapy, and number of and refractoriness to prior therapies, in the MAIC. Overall survival (OS), progression-free survival (PFS), complete response (CR) rate, and overall response (OR) rate were compared. Primary analyses compared infused patients in JULIET (N=106, excluding 8 without lymphodepleting chemotherapy [LDC] and 1 large cell neuroendocrine carcinoma) with efficacy-evaluable set in TRANSCEND (N=256, infused patients). A scenario analysis compared JULIET infused to TRANSCEND primary analysis set (PAS) (N=133, dose level 2, excluding those with ECOG PS 2, prior allogeneic SCT, primary mediastinal B-cell lymphoma, follicular lymphoma [FL] 3B, or transformation from indolent lymphoma besides FL). Sensitivity analyses included JULIET patients with only fludarabine-based LDC or only adjusted significantly different baseline prognostic factors. Safety outcomes were not compared because adverse event management has evolved and differed between the two trials; MAIC is unable to adjust for such differences. Results: After adjusting for differences in baseline characteristics, OS, PFS, and CR were comparable between tisa-cel infused patients and the liso-cel efficacy-evaluable set (Table). The results were consistent across all scenario and sensitivity analyses. OR rate trended higher in the TRANSCEND efficacy-evaluable set (72.7% vs. 62.9%, p=0.07) and was higher in TRANSCEND PAS than in the respectively matched JULIET infused set (74.4% vs. 60.9%, p < 0.05). Conclusions: The MAIC results indicate there is no evidence suggesting differences in OS, PFS and CR between tisa-cel and liso-cel in r/r DLBCL. Analyses using IPD from both trials and/or real-world evidence are warranted to confirm these findings.[Table: see text]
First-MIND: A phase Ib, open-label, randomized study to assess safety of tafasitamab (tafa) or tafa + lenalidomide (LEN) in addition to R-CHOP in patients with newly diagnosed DLBCL.
Authors: Belada David , Kopeckova Katerina , Bergua Juan Miguel , André Marc , Perez Persona Ernesto , Pichler Petra , Klöpfer Pia , Brackertz Bettina , Lohrmann Emanuel , Lahiry Anirban , Shah Neha , Brugger Wolfram , Burke John M. , Nowakowski Grzegorz S. 
Published: June 2021

7540 Background: Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity and phagocytosis. It is FDA-approved with LEN for adult patients (pts) with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation. First-MIND (NCT04134936) is a Phase Ib, open-label, randomized study of tafa + R-CHOP or tafa + LEN + R-CHOP in newly diagnosed DLBCL. Methods: Eligible pts were ≥18 years, treatment-naïve, with histologically confirmed DLBCL not otherwise specified, international prognostic index (IPI) 2–5 and ECOG performance status (PS) 0–2. Pts with known double- or triple-hit and transformed lymphoma were excluded. Treatment (Tx) comprised six 21-day cycles of tafa (12 mg/kg IV, Day [D] 1, 8, 15) + R-CHOP (arm A) or tafa (12 mg/kg IV, D1, 8, 15) + LEN (25 mg orally, D1–10) + R-CHOP (arm B). G-CSF and VTE prophylaxis was mandatory. Primary objective is safety; secondary objectives are ORR, PET-CR rate at end of Tx, PFS, long-term safety, pharmacokinetics, immunogenicity. Results: From Dec 2019 to Aug 2020, 83 pts were screened in Europe and the US; 66 were randomized (33 per arm). Data cut-off for this analysis: 9 Dec 2020; study is ongoing. Median age was 64.5 years (range 20–86). Overall, 30% (20/66) of pts were ≥70 years and many had high-risk disease: IPI 2 29%, IPI 3 46%, IPI 4 26%. ECOG PS: 47% of pts were ECOG PS 0, 44% PS 1, 9% PS 2. Most pts had stage III/IV disease (92%); 46% had bulky disease. All pts experienced a treatment-emergent adverse event (TEAE). Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and 12.1% (arm A) and 66.7% and 30.3% (arm B) of pts, respectively (Table). Serious TEAEs occurred in 42.4% (arm A) and 51.5% (arm B) of pts. There were three deaths, unrelated to tafa and/or LEN (sepsis, urosepsis, and COVID-19 pneumonia). R-CHOP dose intensity was maintained in both arms. Among 60 pts who completed tumor assessments after cycle 3, ORR was 89.7% (arm A) and 93.5% (arm B). Conclusions: These data suggest R-CHOP + tafa or tafa + LEN is tolerable in pts with Tx-naïve DLBCL and that R-CHOP dosing is not affected. Toxicities are similar to those expected with R-CHOP or R-CHOP + LEN. Updated safety and early efficacy data will be presented at the conference. Clinical trial information: NCT04134936. [Table: see text]
Efficacy and safety of zanubrutinib versus rituximab-based chemoimmunotherapy in Waldenström macroglobulinemia (WM): Matching-adjusted indirect comparisons.
Authors: Castillo Jorge J. , Yang Keri , Liu Rongzhe , Wang Yu , Cohen Aileen , Zimmerman Todd M. , Zhao Qian , Gao Xin , Tang Boxiong 
Published: June 2021

7559 Background: Given a lack of WM randomized trials directly comparing zanubrutinib with chemoimmunotherapy, this study aimed to indirectly compare zanubrutinib with bendamustine-rituximab (BR) and with dexamethasone-rituximab-cyclophosphamide (DRC) separately through matching-adjusted indirect comparisons (MAIC). Methods: MAIC were conducted to re-weight the individual data of 102 WM patients (83 relapsed/refractory [R/R] and 19 treatment-naïve [TN]) treated with zanubrutinib in the ASPEN trial (NCT03053440) so that the weighted average baseline characteristics of patients treated with zanubrutinib matched those of 71 R/R patients treated with BR, and 72 TN patients treated with DRC separately. Matching variables for MAIC with BR included age, prior lines of therapy, IgM concentration, International Prognostic Scoring System for WM score, and extramedullary disease (EMD); and for MAIC with DRC included age, platelet count, hemoglobin concentration, and EMD. Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) of comparators were digitized to re-create patient-level data. Comparisons of survival and adverse event incidence between treatments were conducted using Cox proportional hazards models and modified Poisson models. Results: Compared to DRC, zanubrutinib was associated with longer PFS (hazard ratio [HR]: 0.39 [95% confidence interval 0.18-0.82] and 0.35 [0.14-0.86] pre- and post-matching, respectively) and longer OS (HR: 0.56 [0.20-1.53] and 0.47 [0.14-1.62] pre- and post-matching, respectively), and insignificantly higher incidences of neutropenia (risk ratio [RR]: 1.63 [0.71-3.77] and 1.47 [0.58-3.74] pre- and post-matching, respectively). Compared to BR, zanubrutinib was associated with longer PFS (HR: 0.32 [0.15-0.69] and 0.37 [0.15-0.91] pre- and post-matching, respectively), longer OS (HR: 0.31 [0.12, 0.80] and 0.29 [0.10-0.85] pre- and post-matching, respectively), lower incidences of neutropenia (RR: 0.45 [0.26-0.78] and 0.50 [0.27-0.91] pre- and post-matching, respectively) and lower incidences of pneumonia (RR: 0.18 [0.02-1.55] and 0.26 [0.03-2.28] pre- and post-matching, respectively). Conclusions: Zanubrutinib demonstrated longer PFS than DRC, and longer PFS and OS than BR in WM, before and after matching adjustment based on patient characteristics. [Table: see text]
Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial.
Authors: Puig Noemi , Paiva Bruno , Contreras Teresa , Cedena M. Teresa , Rosiñol Laura , Martínez Joaquín , Oriol Albert , Blanchard Maria Jesus , Rios Rafael , Iñigo María Belén , Sureda Balari Anna , Miguel Teodoro Hernández-Garcia , de La Rubia Javier , Krsnik Isabel , José María Moraleda , Orfao Alberto , Blade Joan , F. San-Miguel Jesús , Lahuerta Juan José , Mateos Maria-Victoria 
Published: June 2021

8010 Background: Analysis of minimal residual disease (MRD) in the bone marrow (BM) of patients with multiple myeloma (MM) is accepted by the IMWG to evaluate treatment efficacy and is a well-established prognostic factor. However, there is an unmet need to explore the clinical value of MRD in peripheral blood (PB). Methods: Newly diagnosed MM patients enrolled in the GEM2012MENOS65 trial received six induction (Ind) cycles of bortezomib, lenalidomide, and dexamethasone (VRD) followed by autologous stem cell transplantation (ASCT) and 2 further cycles of consolidation (Cons) with VRD. MRD was analyzed in BM using Next Generation Flow (NGF) and in serum by Mass Spectrometry (MS) using IgG/A/M, κ, λ, free κ and free λ specific beads, both after Ind, at day 100 after ASCT, and after Cons. Sequential samples from the first 184 patients were analyzed. Results: Results of both methods were in agreement (NGF+/MS+ and NGF-/MS-) in 83% of cases post-Ind (152/184), 80% post-ASCT (139/174) and 76% post-Cons (128/169). Stratifying by the log range of MRD by NGF, discordances (NGF+/MS- and NGF-/MS+) seemed to increase at the lower MRD ranges, being 22%, 21% and 19% from ≥10−5 to <10−4 and 21%, 21%, 23% at ≥x10−6(post-Ind, ASCT and Cons, respectively). Analysis of discordances showed that they could be partly explained by the higher percentages of cases found to be positive by MS as compared by NGF at part of the time-points analyzed and at each log range of MRD. From ≥10−5 to <10−4, MRD was detected by NGF in 36%, 28%, 20% of cases post-Ind, ASCT and Cons, respectively vs MS in 37%, 29%, 21% of them; at ≥x10−6, NGF was positive in 11%, 14%, 19% of cases vs MS in 23%, 19% and 16% of them. Considering NGF as a reference, the negative predictive value (NPV) of MS per MRD range (≥10−5 to <10−4 and ≥x10−6, respectively) was: post-Ind: 83% (p<0,0001), 94% (p=0,034); post-ASCT 86% (p<0,0001), 90% (p=0,022); post-Cons 89% (p<0,0001), 85% (p=0,0469). Despite these discordances, the prognostic value of each technique in terms of undetectable MRD and progression-free survival (PFS) was consistent at all time-points (Table) and further, discordant cases (NGF+/MS- and NGF-/MS+) did not display a significantly different PFS as compared to NGF-/MS- cases. Conclusions: The results of MRD assessed by NGF in BM and by MS in PB show a significant concordance and are associated with a similar prognostic value analyzed in terms of PFS. Given its high NPV, MRD in peripheral blood by MS provides a gateway for BM aspiration/biopsy and MRD assessment by NGF.[Table: see text]
Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis.
Authors: Facon Thierry , Moreau Philippe , Martin Thomas G. , Spicka Ivan , Oriol Albert , Koh Youngil , Lim Andrew , Mikala Gabor , Rosiñol Laura , Yağci Münci , Cavo Michele , Yong Kwee , Risse Marie-Laure , Asset Gaëlle , Schwab Sandrine , Martinez Gracia 
Published: June 2021

8026 Background: A prespecified interim efficacy analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P=0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD-) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts aged <70 and ≥70 years. Methods: Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n=179) or Kd (n=123). The primary end point was PFS, as assessed by an independent response committee. We compared outcomes in pts <70 vs ≥70 years; division into different or additional age groups resulted in smaller sample sizes. Results: Of the 302 randomized pts, 71.5% were aged <70 years (Isa-Kd: 70.9%; Kd: 72.4%) and 28.5% were aged ≥70 years (Isa-Kd: 29.1%; Kd: 27.6%). Consistent with the significant improvement of PFS in the overall population, the addition of Isa to Kd resulted in improved PFS independently of age (Table). The CR, ≥very good partial response (VGPR), and MRD- rates were higher with Isa-Kd vs Kd. Within the Isa-Kd arm, CR rate and ≥VGPR rate were similar in elderly and younger pts. MRD- was observed in 32.3% of younger pts and 23.1% of elderly pts with Isa-Kd. In both arms, Grade ≥3 and serious treatment-emergent adverse events (TEAEs) were more frequently reported in elderly pts vs pts <70 years old (Table). For both age groups, the incidence of Grade ≥3 TEAEs was higher whereas the incidence of serious TEAEs was similar between Isa-Kd and Kd. In the elderly subgroup, 3 (5.9%) pts receiving Isa-Kd and 1 (2.9%) receiving Kd had fatal TEAEs (Isa-Kd, infection; Kd, general health deterioration due to progressive disease). The most common Grade ≥3 TEAEs in pts aged <70 and ≥70 years treated with Isa-Kd vs Kd were hypertension (18.3% vs 17.0% [<70 years] and 25.5% vs 26.5% [≥70 years]) and pneumonia (14.3% vs 9.1% [<70 years] and 21.6% vs 20.6% [≥70 years]). Conclusions: The addition of Isa to Kd improved PFS and quality of response in elderly pts, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA study population. Isa-Kd provides a potential new treatment option for elderly pts with RMM. Funding: Sanofi. Clinical trial information: NCT03275285. [Table: see text]
KEYNOTE-799: Phase 2 trial of pembrolizumab plus platinum chemotherapy and radiotherapy for unresectable, locally advanced, stage 3 NSCLC.
Authors: Jabbour Salma K. , Lee Ki Hyeong , Frost Nicolaj , Breder Valeriy Vladimirovich , Kowalski Dariusz M. , Alawin Issam Abdelkarim , Levchenko Evgeny , Reguart Noemi , Martinez-Marti Alex , Houghton Baerin , Paoli Jean-Baptiste , Safina Sufia , Park Keunchil , Komiya Takefumi , Sanford Amy , Boolell Vishal , Liu Hong , Samkari Ayman , Keller Steven M. , Reck Martin 
Published: June 2021

8512 Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5% in cohort B (nonsquamous, n = 61), and grade ≥3 pneumonitis in 8.0% and 7.9% of pts, respectively. Here, we present results for all pts enrolled in KEYNOTE-799. Methods: This nonrandomized, multisite, open-label phase 2 trial enrolled pts aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA‒C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received 1 cycle of carboplatin AUC 6 and paclitaxel 200 mg/m2 and pembro 200 mg. After 3 wks, pts received carboplatin AUC 2 and paclitaxel 45 mg/m2 QW for 6 wks and 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2,and pembro 200 mg Q3W, and TRT in cycles 2 and 3. All pts received an additional 14 cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Efficacy and safety were assessed in all pts as-treated. Results: Of 216 pts enrolled in KEYNOTE-799 (cohort A, n = 112; cohort B, n = 104), 112 in cohort A and 102 in cohort B received treatment. As of October 28, 2020, the median (range) time from first dose to database cutoff was 18.5 (13.6–23.8) mo in cohort A and 13.7 (2.9–23.5) mo in cohort B. ORR (95% CI) was 70.5% (61.2%‒78.8%) in cohort A and 70.6% (60.7%‒79.2%) in cohort B. Median DOR was not reached in either cohort (Table). ORR was similar regardless of PD-L1 status ([TPS <1% and TPS ≥1%]; Cohort A, 66.7% and 75.8%; Cohort B, 71.4% and 72.5%) and tumor histology (Cohort A, squamous, 71.2% and nonsquamous, 69.2%). Grade ≥3 pneumonitis occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3‒5 treatment-related AEs occurred in 72 pts (64.3%) in cohort A and 51 (50.0%) in cohort B. Conclusions: Pembro plus cCRT continues to demonstrate promising antitumor activity, regardless of PD-L1 TPS and tumor histology, and manageable safety in pts with previously untreated, locally advanced, stage III NSCLC with longer follow-up. Clinical trial information: NCT03631784. [Table: see text]
Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.
Authors: Gale Davina , Heider Katrin , Perry Malcolm , Marsico Giovanni , Ruiz-Valdepeñas Andrea , Rundell Viona , Wulff Jerome , Sharma Garima , Howarth Karen , Gilligan David , Harden Susan , Rassl Doris M. , Rintoul Robert , Rosenfeld Nitzan 
Published: June 2021

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to > 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value < 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.