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Background The efficacy and safety of certolizumab pegol ( CZP) in moderate-to-severe Crohn's disease were demonstrated in two 26-week double-blind studies ( PRECi SE 1 & 2). Aim To report the safety and efficacy outcomes of long-term, CZP therapy from PRECi SE 3, in which patients received treatment up to 7 years treatment. Methods Patients completing PRECi SE 1 or 2 were eligible to enter PRECi SE 3 in which they received CZP 400 mg, open-label, every 4 weeks (without additional induction therapy) for up to 7 years, for up to 91 doses from study start. Safety (adverse events, including infections and malignancies) and efficacy (Harvey-Bradshaw Index, faecal calprotectin, C-reactive protein) were prospectively monitored. Remission was analysed using observed cases, last observation carried forward imputation and nonresponder imputation. Results A total of 595 patients entered the study; 117 (20%) completed 7 years. Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% (years 1-7 respectively). During 1920 patient-years of exposure to CZP, no new safety signals were observed. Incidence rates (new cases/100 patient-years) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively. No lymphoproliferative malignancies were reported. Clinical remission rates were ≥68% at each year (observed cases); rates by last observation carried forward and nonresponder imputation were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7 respectively. Conclusion Certolizumab pegol was well tolerated in the long-term treatment of Crohn's disease, with sustained remission in some patients continuing in the study for up to 7 years. ClinicalTrials.gov identifier NCT00552058. [ABSTRACT FROM AUTHOR]

Purpose: In RE-MIND2 (NCT04697160), patient-level outcomes from the L-MIND study (NCT02399085) of tafasitamab plus lenalidomide were retrospectively compared with patient-level matched observational cohorts treated with National Cancer Care Network (NCCN)/European Society for Medical Oncology (ESMO)-listed systemic therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL)., Patients and Methods: Data were collected from health records of eligible patients aged ≥18 years with histologically confirmed DLBCL who had received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients from L-MIND were matched with patients from the RE-MIND2 observational cohort using estimated propensity score-based 1:1 nearest-neighbor matching, balanced for nine covariates. The primary analysis compared tafasitamab plus lenalidomide with patients who received any systemic therapy for R/R DLBCL (pooled in one cohort) or bendamustine plus rituximab (BR) or rituximab plus gemcitabine and oxaliplatin (R-GemOx; as two distinct cohorts). The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and time-to-event outcomes., Results: In RE-MIND2, 3,454 patients were enrolled from 200 sites in North America, Europe, and Asia-Pacific. Strictly matched pairs of patients consisted of tafasitamab plus lenalidomide versus systemic therapies pooled (n = 76 pairs), versus BR (n = 75 pairs), and versus R-GemOx (n = 74 pairs). Significantly prolonged OS was reported with tafasitamab plus lenalidomide versus systemic pooled therapies [hazard ratios (HR): 0.55; P = 0.0068], BR (HR: 0.42; P < 0.0001), and R-GemOx (HR: 0.47; P = 0.0003)., Conclusions: RE-MIND2, a retrospective observational study, met its primary endpoint, demonstrating prolonged OS with tafasitamab plus lenalidomide versus BR and R-GemOx. See related commentary by Cherng and Westin, p. 3908., (©2022 The Authors; Published by the American Association for Cancer Research.)

Introduction: Tafasitamab plus lenalidomide (TAFA + LEN) received accelerated US Food and Drug Administration approval and conditional European Medicines Agency approval for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for autologous stem cell transplant. This study investigates the relative efficacy of TAFA + LEN versus comparator treatments., Methods: Matching-adjusted indirect comparisons (MAICs) of TAFA + LEN were performed using data from L-MIND, and comparator studies assessing rituximab-based combination therapies, including polatuzumab vedotin + bendamustine + rituximab (POLA + BR) bendamustine + rituximab (BR), and gemcitabine + oxaliplatin + rituximab (R-GEMOX) to provide relative efficacy estimates for overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and complete response rate (CRR). Patient-level data from L-MIND were weighted to match reported distributions of clinically validated prognostic factors and effect modifiers in comparator trials. MAIC results versus multiple BR studies were pooled using meta-analysis., Results: MAICs were feasible versus POLA + BR and BR. Compared to POLA + BR, TAFA + LEN was associated with significantly longer DOR [hazard ratio (HR) 0.34 (95% CI 0.12, 0.98); p = 0.045]. Due to concerns about the proportional hazard assumption for OS and PFS, separate HRs were estimated before and after 4 months of follow-up. OS after 4 months, was significantly greater for TAFA + LEN versus POLA + BR [HR 0.41 (95% CI 0.19, 0.90); p = 0.026]. Compared with BR, TAFA + LEN was associated with significantly improved OS [GO29365 comparator trial: HR 0.39 (95% CI 0.18, 0.82); p = 0.014], PFS (pooled data: HR 0.39 (95% CI 0.29, 0.53); p < 0.001], DOR [pooled data: HR 0.35 (95% CI 0.25, 0.50); p < 0.001], and CRR [pooled data: odds ratio 2.43 (95% CI 1.33, 4.41); p = 0.004]., Conclusion: In MAIC analyses, treatment with TAFA + LEN for R/R DLBCL provided better OS and PFS outcomes than standard treatment regimens. Validation from large, randomized, phase 3 clinical trials is required to confirm these results., (© 2022. Incyte Corporation.)

Purpose: Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination., Patients and Methods: Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide-treated patients (L-MIND). Key eligibility criteria were aligned with L-MIND. Estimated propensity score-based Nearest Neighbor 1:1 Matching methodology balanced the cohorts for nine prespecified prognostic baseline covariates. The primary endpoint was investigator-assessed best overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and overall survival (OS)., Results: Data from 490 patients going through lenalidomide monotherapy were collected; 140 qualified for matching with the L-MIND cohort. The primary analysis included 76 patients from each cohort who received a lenalidomide starting dose of 25 mg/day. Cohort baseline covariates were comparable. A significantly better ORR of 67.1% (95% confidence interval, 55.4-77.5) was observed for the combination therapy versus 34.2% (23.7-46.0) for lenalidomide monotherapy [odds ratio, 3.89 (1.90-8.14); P < 0.0001]. Higher CR rates were achieved with combination therapy compared with lenalidomide monotherapy [39.5% (28.4-51.4) vs. 13.2% (6.5-22.9)]. Survival endpoints favored combination therapy. Lenalidomide monotherapy outcomes were similar to previously published data., Conclusions: RE-MIND enabled the estimation of the additional treatment effect achieved by combining tafasitamab with lenalidomide in patients with R/R DLBCL., (©2021 The Authors; Published by the American Association for Cancer Research.)

Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months' follow-up. Patients were aged >18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months' follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.

Background: Patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for autologous stem-cell transplantation have poor outcomes and few treatment options. Tafasitamab (MOR208) is an Fc-enhanced, humanised, anti-CD19 monoclonal antibody that has shown preclinical and single-agent activity in patients with relapsed or refractory B-cell malignancies. Preclinical data suggested that tafasitamab might act synergistically with lenalidomide. We aimed to assess the antitumour activity and safety of tafasitamab plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for autologous stem-cell transplantation., Methods: In this multicentre, open-label, single-arm, phase 2 study (L-MIND), patients older than 18 years with histologically confirmed diffuse large B-cell lymphoma, who relapsed or had refractory disease after previous treatment with one to three systemic regimens (with at least one anti-CD20 therapy), were not candidates for high-dose chemotherapy and subsequent autologous stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, and had measurable disease at baseline were recruited from 35 academic and community hospitals in ten countries. Patients received coadministered intravenous tafasitamab (12 mg/kg) and oral lenalidomide (25 mg/day) for up to 12 cycles (28 days each), followed by tafasitamab monotherapy (in patients with stable disease or better) until disease progression. The primary endpoint was the proportion of patients with an objective response (centrally assessed), defined as a complete or partial response according to the 2007 International Working Group response criteria for malignant lymphoma. Antitumour activity analyses are based on all patients who received at least one dose of both tafasitamab and lenalidomide; safety analyses are based on all patients who received at least one dose of either study medication. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, NCT02399085., Findings: Between Jan 18, 2016, and Nov 15, 2017, 156 patients were screened: 81 were enrolled and received at least one dose of either study medication, and 80 received at least one dose of both tafasitamab and lenalidomide. Median follow-up was 13·2 months (IQR 7·3-20·4) as of data cutoff on Nov 30, 2018. 48 (60%; 95% CI 48-71) of 80 patients who received tafasitamab plus lenalidomide had an objective response: 34 (43%; 32-54) had a complete response and 14 (18%; 10-28) had a partial response. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (39 [48%] of 81 patients), thrombocytopenia (14 [17%]), and febrile neutropenia (ten [12%]). Serious adverse events occurred in 41 (51%) of 81 patients. The most frequently reported serious adverse events (in two or more patients) were pneumonia (five [6%]), febrile neutropenia (five [6%]), pulmonary embolism (three [4%]), bronchitis (two [2%]), atrial fibrillation (two [2%]), and congestive cardiac failure (two [2%])., Interpretation: Tafasitamab in combination with lenalidomide was well tolerated and resulted in a high proportion of patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem-cell transplantation having a complete response, and might represent a new therapeutic option in this setting., Funding: MorphoSys., (Copyright © 2020 Elsevier Ltd. All rights reserved.)