Rituxan (rituximab)

Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma.

Complete remission was achieved with a reduced immunomodulatory drug dosage and rituximab therapy. She has been alive for 8 months postoperatively without recurrence. This case suggests that PTLD should be considered in assessing patients presenting with abdominal symptoms following organ transplantation.

The association of Cladribine (CDA) with rituximab (R) is the standard first-line treatment in fit HCL and HCL variant patients. BRAF and BTK inhibitors are options in relapsed/refractory HCL patients. The optimal treatment sequences remain to be determined.

P2, N=150, Not yet recruiting, PolTREG S.A.

P3, N=182, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P1, N=20, Completed, Noah Merin | Active, not recruiting --> Completed | N=30 --> 20 | Trial completion date: Nov 2031 --> Nov 2024

P=N/A, N=60, Completed, Shandong Provincial Hospital for Skin Diseases & Shandong First Medical University; Shandong Provincial Hospital for Skin Diseases & Shandong

P4, N=58, Completed, The First Affiliated Hospital of Zhejiang University School of Medicine; The First Affiliated Hospital of Zhejiang University School of Medicine

P4, N=54, Recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P3, N=428, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=120, Completed, Peking University People's Hospital; Department of Neurology, Peking University People’s Hospital | Not yet recruiting --> Completed

P2/3, N=210, Recruiting, University of Birmingham | Active, not recruiting --> Recruiting

P2, N=125, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Recruiting | N=80 --> 125 | Trial primary completion date: Sep 2027 --> Apr 2025

P2, N=17, Completed, University College, London | Trial completion date: Jun 2023 --> Feb 2024

P2, N=18, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025

P4, N=8, Not yet recruiting, Alexion Pharmaceuticals, Inc. | Trial completion date: Sep 2028 --> Jan 2029 | Trial primary completion date: Sep 2028 --> Jan 2029

Introduction – We previously reported the efficacy and safety results of a combination of ibrutinib with rituximab in patients (pts) with mantle cell lymphoma (MCL) ≥ 65 years. Conclusions – Chemotherapy-free frontline therapy with AR is highly effective, safe, induces deep MRD negative responses and alters immune landscape in older pts with MCL. Randomized studies are needed to confirm whether this regimen can be the new first line standard treatment for older MCL patients.

Acalabrutinib in combination with BR provides a significant PFS benefit in pts with previously untreated MCL, including those with high-risk features. Furthermore, the addition of acalabrutinib to BR provided a greater PFS effect among pts in the ABR arm with the longest exposure to acalabrutinib. The PFS improvement may be partially driven by the contribution of acalabrutinib to sustained MRD-negative status and deepened responses after the end of induction.

After transformation, tFL samples showed a reduction in T follicular helper cells (p=0.008) and an increase in immunosuppressive M2-like macrophages and neutrophils (p<0.001 and p=0.028, respectively). By elucidating the distinct molecular and immune landscapes of FL at the time of diagnosis and transformation, this study underscores the importance of immune microenvironment in FL transformation and patient outcome.

RFS of these 8 patients after purine analog monotherapy was also inferior compared to a control group of 34 patients who received cladribine monotherapy and began prospective follow-up before any relapses (19.9 vs 271.8 months, p<0.0001). Non-V600E BRAF mutations were observed in patients with classic HCL immunophenotype, some of which were co-mutations in BRAF with V600E. In view of the inferior RFS in these patients when purine analog was not combined with rituximab, these mutations may constitute a higher risk for relapse or chemoresistance. While those with BRAF V600 mutations might be candidates for BRAF inhibition, those with other BRAF mutations represent an opportunity for development of other specific inhibitors, not only for HCL/HCLv, but also for other malignancies.

Three pts were unevaluable for progression at 2y due to non-progression events including a second malignancy, sudden death, and hemolytic anemia requiring rituximab... Circulating tumor DNA is detectable in baseline plasma of >90% pts with untreated FL. Quantitative ctDNA levels correlate with both FLIPI and TMTV and are associated with earlier need for treatment. Serial ctDNA monitoring shows fluctuating levels that correlate with tumor burden on CT which provides a non-invasive method to monitor disease.

We recently demonstrated that INO can be added safely to a non-myeloablative conditioning of bendamustine, fludarabine, and rituximab in patients with indolent lymphoid malignancies who required an allogeneic hematopoietic transplantation (HCT) (Am J Hematol 2024)...Patients who received transplants from MUDs received an additional dose of methotrexate 5 mg/m2 on day +11 and 1 mg/kg of rabbit anti-thymocyte globulin IV on days -1 and -2 before HCT...The patient who was in CR2 at transplant had Ph+ ALL and was maintained on ponatinib after HCT. Key prior therapies in ALL patients included blinatumomab (n=5) and INO (n=5)... Our conclusions are limited by the small number of patients due to slow accrual. However, our data suggest that INO is safe when combined with a melphalan plus fludarabine HCT conditioning regimen. The survival outcomes are encouraging and need to be validated in a larger number of patients.

Our series reinforces the poor prognosis of advanced stage HGBCL with less intensive regimens such as R-CHOP. In contrast to several other series, MYC/BCL6-R are associated with inferior OS in our cohort, which may be secondary to a higher frequency of CNS relapse despite similar administration of CNS prophylaxis. Indeed, there was no clear impact of CNS prophylaxis/IT-chemotherapy as relapses were distributed equally between those who did or did not receive prophylaxis.

Induction with 3 cycles of bendamustine and rituximab followed by 3 cycles of cytarabine and rituximab (BR/CR) is associated with high complete metabolic response (CMR) and uMRD rates (Armand et al., BJH 2016; Merryman et al., Blood Adv 2020). Bruton’s tyrosine kinase inhibitors (BTKi) including ibrutinib and acalabrutinib (A) in combination with CIT are highly effective in MCL (Wang et al., EHA 2024, LBA 3439)... High PET/CT CMR uMRD rates were seen in all 3 arms. BR/CR can be considered as a standard induction in pts ≤ 70. Addition of acalabrutinib to the standard arm added toxicity without improvement in efficacy, suggesting acalabrutinib should be avoided during Ara-C cycles.

This study demonstrates that the ALR regimen has high rates of durable complete and molecular responses, and is feasible as a time-limited initial therapy for patients with both TP53 wild type and mutant MCL. The ALO regimen is feasible with encouraging initial safety and efficacy. MRD and cfDNA analyses provide real-time and non-invasive monitoring of molecular response and mutational evolution, which warrants further evaluation in response-adapted strategy.

For patients (pts) with R/R FL, rituximab + lenalidomide (R2) is an approved and widely accepted regimen based on results from the AUGMENT trial (overall response rate [ORR], 78%; complete response [CR] rate, 34%; estimated 2-y progression-free survival [PFS], 58%). With more than 2 y of follow-up, fixed-duration epcoritamab + R2 continued to show deep and durable responses (CR rate, 87%; estimated 24-mo DOCR, 75%) in pts with R/R FL, irrespective of high-risk features. Considering limitations of cross-trial comparisons, these results (estimated 2-y PFS, 70%) compare favorably with those reported for R2 alone in the AUGMENT trial (estimated 2-y PFS, 58%). The depth of responses was underscored by MRD negativity in 88% of evaluable pts.

P1/2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Phase classification: P1b/2 --> P1/2

P1, N=18, Not yet recruiting, Guangdong Provincial People's Hospital

P2, N=39, Recruiting, University of Rochester | Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2026

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

P2, N=622, Recruiting, Genmab | Trial completion date: Jun 2031 --> Nov 2032 | Trial primary completion date: Jun 2031 --> Nov 2032

To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. The most common grades 3-4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

P2, N=30, Active, not recruiting, David Bond, MD | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

Currently, the first-line treatment regimen for DLBCL is still rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which significantly improves outcomes for DLBCL patients. In conclusion, we report for the first time that rituximab induces ferroptosis in lymphoma cells, at least partially through the SLC7A11/GPX4 axis. We also identify targeting ferroptosis as a promising therapeutic option for both sensitive cells and resistant cells in the treatment of DLBCL.

P=N/A, N=108, Recruiting, Zhongshan Ophthalmic Center, Sun Yat-sen University | Trial completion date: Dec 2027 --> Dec 2029 | Trial primary completion date: Dec 2027 --> Dec 2029

The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treatment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.

Because the patient had a MALT1 translocation with trisomy 18q21, it was thought that this gastric MALT lymphoma developed independently of H. pylori infection and progressed.

To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P1/2, N=53, Completed, BeiGene | Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> Aug 2024

P1, N=174, Recruiting, Celgene | Trial primary completion date: Sep 2024 --> Dec 2024