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The MZL cohort is planned to include 78 patients, who will receive IV odronextamab monotherapy until disease progression or other protocol-defined reason for treatment discontinuation. In the Phase 1 ELM-1 study, odronextamab monotherapy showed antitumor activity and a manageable safety profile in a range of I R i / I R i B-NHL subtypes, including MZL ( I n i = 6; ORR 67%) (Bannerji et al. B Introduction: b MZL is a heterogeneous disease comprising 3 subtypes, extra-nodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and splenic MZL. [Extracted from the article]

B Conclusion: b HDC-ASCT based on conditioning regimen consisted of carmustine, etoposide and thiotepa (BET) is a relatively safe and highly effective treatment for PCNSL patients. B Introduction: b High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is now the preferred consolidation strategy for young PCNSL patients. At the end of induction 29 (64.5%) patients obtained CR/CRun (19/10 respectively), with additional 5 (11%) patients with no evidence of disease at baseline, and 11 (24.5%) in PR, based on standard CT/MRI assessment. [Extracted from the article]

Background: Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit in patients with relapsed/refractory (R/R) B-cell malignancies. In this phase 2 study (CITADEL-205; NCT03235544, EudraCT 2017-003148-19), the efficacy and safety of parsaclisib was evaluated in patients with R/R mantle cell lymphoma (MCL)., Methods: Patients ≥18 years old with pathologically confirmed R/R MCL and prior treatment with 1-3 systemic therapies, with (cohort 1) or without (cohort 2) previous Bruton kinase inhibitor (BTKi) treatment, received oral parsaclisib 20 mg once-daily (QD) for 8 weeks, then either parsaclisib 20 mg once-weekly (weekly dosing group [WG]) or parsaclisib 2.5 mg QD (daily dosing group [DG]). The primary endpoint was objective response rate (ORR)., Findings: At the primary analysis data cutoff on January 15, 2021, 53 patients in cohort 1 (BTKi-experienced) (WG, n = 12; DG: n = 41) and 108 patients in cohort 2 (BTKi-naive) (WG, n = 31; DG: n = 77) had received parsaclisib monotherapy. The BTKi-experienced cohort was closed after an interim analysis demonstrated limited clinical benefit. In the BTKi-naive cohort, the ORR (95% CI) for DG (dosing selected for further study) was 70.1% (58.6%-80.0%), with a complete response rate (95% CI) of 15.6% (8.3%-25.6%) and a median duration of response (95% CI) of 12.1 (9.0-not evaluable) months. Treatment-emergent adverse events (TEAEs) occurred among 90.7% (98/108) of all treated patients in the BTKi-naive cohort. Grade ≥3 TEAEs occurred among 62.0% (67/108) of patients, including diarrhoea (13.9%, 15/108) and neutropenia (8.3%, 9/108). Parsaclisib interruption, reduction, or discontinuation due to TEAEs occurred among 47.2% (51/108), 8.3% (9/108), and 25.0% (27/108) of patients, respectively. Fatal TEAEs were experienced by six patients and determined to be treatment-related in one patient., Interpretation: Parsaclisib, a potent, highly selective, PI3Kδ inhibitor demonstrated meaningful clinical benefits and a manageable safety profile (25.0% discontinuation rate, low incidences of individually reported grade ≥3 or serious adverse events) in R/R MCL patients with no prior BTKi therapy. Limited clinical benefit was observed with parsaclisib monotherapy in patients who had previously received BTKi treatment. Future development of PI3K inhibitors for NHL will require further investigation of dose optimisation to improve safety and long-term survival., Funding: Incyte Corporation., Competing Interests: PLZ reports consulting or advisory role, and involvement of speakers bureau for Beigene, Bristol Myers Squibb, Celltrion, EUSA Pharma, Gilead, Incyte Corporation, Janssen-Cilag, Kyowa Kirin, Merck Sharp & Dohme, Novartis, Roche, Servier, Takeda, and TG Therapeutics; advisory role for ADC Therapeutics, Sandoz, and Secura Bio. MTrněný reports honoraria, consulting or advisory role, travel and accommodations expenses for AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen, Roche, and Takeda; honoraria, consulting or advisory role for Amgen, Incyte Corporation, and MorphoSys. VR reports research funding for ArgenX and Astex; membership on a board or advisory committee for Bristol Myers Squibb, Epizyme, Gilead, GlaxoSmithKline, Incyte Corporation, Infinity, Merck Sharp & Dohme, Nanostring, and Roche; membership on a board or advisory committee, honoraria for PharmaMar; membership on a board or advisory committee, consultancy for Servier. VRZ reports consulting or advisory role, speakers bureau for Gentili, Gilead, Italfarmaco, Janssen, Merck Sharp & Dohme, Roche, Servier, and Takeda. JW reports research funding for GlaxoSmithKline, Novartis, and Roche; advisory role and lecture honoraria for AbbVie, Amgen, Celgene, Gilead, Janssen, Novartis, Roche, Servier, and Takeda. GR reports consulting or advisory role, and involvement of speakers bureau for Bristol Myers Squibb, Celgene, Janssen, Roche, and Takeda; consulting or advisory role for EUSA Pharma. MC reports research funding for Amgen, Astra Zeneca, BeiGene, Bristol Meyers, Celgene, Gilead, Incyte, Innocare, Johnson and Johnson, Merck, Pharmacyclics; consulting for BeiGene, Epizyme, Gilead. CD reports advisory board for AbbVie, AstraZeneca, Beigene, and Janssen; travel and accommodation expenses for AbbVie, AstraZeneca, and Janssen. CP reports advisory board for Abbvie, Incyte Corporation, and Janssen. FP reports consulting or advisory role, speakers bureau, travel and accommodations expenses for AbbVie (Investigator in sponsored clinical trials), Amgen, Jazz Pharmaceuticals, and Novartis Pharma SAS; consulting or advisory role, travel and accommodations expenses for Daiichi Sankyo; travel and accommodations expenses for Janssen; research funding for Novartis Pharma SAS (Institutional). WJurczak reports research funding for Bayer, Gilead, Incyte Corporation, Mei Pharma, and TG Therapeutics. MTaszner reports consulting or advisory role, travel and accommodations expenses for Roche and Takeda. SP reports honoraria for AbbVie, Bristol Myers Squibb, Celgene, Gilead, and Janssen. FZ reports employment and stock ownership for Incyte Corporation. DJD reports former employment and stock ownership for Incyte Corporation. WJiang reports former employment and stock ownership for Incyte Corporation. AG reports employment and stock ownership for Incyte Corporation. AM reports consultancy, membership on an entity's board of directors or advisory committees, research funding, speakers bureau for Seattle Genetics and TG Therapeutics; research funding for Affimed, Celgene/Bristol Myers Squibb, fortyseven Inc/Gilead, Innate Pharmaceuticals, Juno Pharmaceuticals/Bristol Myers Squibb, Kite/Gilead, Merck, OncoTartis, Roche-Genentech, and Takeda; consultancy, membership on an entity's board of directors or advisory committees, research funding, speakers bureau for Incyte Corporation. JHC, VD, and PV report no relevant disclosures to declare., (© 2023 The Authors.)

The efficacy of salvage treatment of diffuse large B-cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with iphosphamide, etoposide and cytarabine (O-IVAC) was evaluated in a single-arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end-point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end-points included progression-free survival (PFS), event-free survival (EFS), overall survival (OS) and safety. Seventy-seven patients received salvage treatment with O-IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O-IVAC was 54.5%. The median duration of study follow-up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment-related mortality was 15.5%. O-IVAC showed a high response rate in a difficult-to-treat population and is an attractive treatment to bridge to potentially curative therapies., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The molecular target for the classical complement pathway (CP) is defined by surface-bound immunoglobulins. Therefore, numerous anticancer monoclonal antibodies (mAbs) exploit the CP as their effector mechanism. Conversely, the alternative complement pathway (AP) is spontaneously induced on the host and microbial surfaces, but complement inhibitors on host cells prevent its downstream processing. Gain-of-function (GoF) mutations in the AP components that oppose physiological regulation directly predispose carriers to autoimmune/inflammatory diseases. Based on the homology between AP and CP components, we modified the CP component C2 so that it emulates the known pathogenic mutations in the AP component, factor B. By using tumor cell lines and patient-derived leukemic cells along with a set of clinically approved immunotherapeutics, we showed that the supplementation of serum with recombinant GoF C2 variants not only enhances the cytocidal effect of type I anti-CD20 mAbs rituximab and ofatumumab, but also lowers the threshold of mAbs necessary for the efficient lysis of tumor cells and efficiently exploits the leftovers of the drug accumulated in patients' sera after the previous infusion. Moreover, we demonstrate that GoF C2 acts in concert with other therapeutic mAbs, such as type II anti-CD20, anti-CD22, and anti-CD38 specimens, for overcoming cancer cells resistance to complement attack.