bims-hemali 2025-01-05 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–01–05
sixteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Bortezomib With High-dose Melphalan Conditioning Regimen in Newly Diagnosed Multiple Myeloma Patients: Long-term Follow-up.
Long-term remission following CAR-T therapy in a patient with transformed follicular lymphoma relapse after allogeneic stem cell transplantation.
Cost-Effectiveness of Frontline TKI Strategies for Chronic Myeloid Leukemia Patients: in Pursuit of Treatment-Free Remission and Dose Reduction.
Zanubrutinib plus R-CHOP for the treatment of newly diagnosed double-expressor lymphoma: A phase 2 clinical study.
Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation.
Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial.
Optimal use of BTK inhibitors in Waldenström's macroglobulinemia: combination or single drug approach?
One-Day Brentuximab-Bendamustine (120 mg/m2) Every 21 Days is a Feasible, Safe and Effective Treatment for Relapsed/Refractory Hodgkin Lymphoma.
Selinexor in combination with venetoclax and decitabine in patients with refractory myelodysplastic syndrome previously exposed to hypomethylating agents: three case reports.
Tandem Versus Single Autologous Stem Cell Transplantation for High-Risk Multiple Myeloma in the Era of Novel Agents: A Real-World Study of China.
Successful Treatment of a Patient Presenting with Simultaneous Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma: A Case Report.
[Efficacy and Safety of Flumatinib and Imatinib as First-line Treatments for Newly-diagnosed Chronic Myeloid Leukemia in Chronic Phase: A Real-world Study].
Nodular lymphocyte-predominant Hodgkin lymphoma revisited: current management strategies and future perspectives.
A Single-Center Experience: Integrated Management in Primary Central Nervous System Lymphoma.
Safety and efficacy of CD33-targeted CAR-NK cell therapy for relapsed/refractory AML: preclinical evaluation and phase I trial.
Antisense oligonucleotides-based approaches for the treatment of multiple myeloma.

In Vivo. 2025 Jan-Feb;39(1):39(1): 340-345

Bortezomib With High-dose Melphalan Conditioning Regimen in Newly Diagnosed Multiple Myeloma Patients: Long-term Follow-up.

Risa Nishiyama, Toshiya Kagoo, Hironori Ueno, Akihiro Yokoyama.

   BACKGROUND/AIM: Autologous stem cell transplantation (ASCT) is the standard strategy after induction therapy for newly diagnosed transplant-eligible multiple myeloma. High-dose melphalan (HDM) conditioning has been the recommended treatment regimen for a long time. No other conditioning regimen has been proven safer and more effective. Because bortezomib has a synergistic effect with melphalan, bortezomib with HDM (Bor-HDM) as a conditioning regimen has shown favorable outcomes, improved complete response rates after ASCT, and no prolonged hematological toxicities. However, few studies have reported long-term follow-up data. This study aimed to evaluate the long-term progression-free survival (PFS) and overall survival (OS) of patients receiving Bor-HDM conditioning, compared to those treated with HDM alone.
PATIENTS AND METHODS: This single-center retrospective study included 36 patients newly diagnosed with transplant-eligible myeloma from 2008 to 2020. In total, 15 patients received a Bor-HDM regimen, while 21 patients received HDM as a conditioning regimen. The probabilities of PFS and OS were plotted using the Kaplan-Meier method. All statistical analyses were performed using EZR software.
RESULTS: After a median follow up of 77 months, no severe hematological toxicities were observed. The PFS and OS rates in the Bor-HDM group as compared with the HDM group were 0.762 vs. 0.60 (p=0.409) and 0.80 vs. 0.904 (p=0.476) respectively. No significant differences were observed between the two groups.
CONCLUSION: These long-term results show that Bor-HDM is a safe and effective option for ASCT conditioning regimens.

Keywords:  Multiple myeloma; autologous stem cell transplantation; bortezomib; high-dose melphalan; transplant eligible

DOI:  https://doi.org/10.21873/invivo.13833
Ann Hematol. 2024 Dec 30.

Long-term remission following CAR-T therapy in a patient with transformed follicular lymphoma relapse after allogeneic stem cell transplantation.

Ryuta Kubo, Koichi Onodera, Yasushi Onishi, Noriko Fukuhara, Hideo Harigae.

  Follicular lymphoma (FL) may undergo histological transformation (HT) into a more aggressive lymphoma. Although rituximab for B-cell non-Hodgkin lymphomas (B-NHL) has greatly improved the overall survival (OS) of patients with transformed FL (tFL), relapse after anthracycline-based chemoimmunotherapy has a poor prognosis. CD19-targeting chimeric antigen receptor-modified T-cell (CAR-T) therapy is a promising treatment for relapsed or refractory (r/r) large B-cell lymphoma (LBCL), including tFL. However, lymphopenia and reduced T-cell fitness caused by bendamustine exposure for treatment of underlying FL may impair the feasibility and reduce the efficacy of CAR-T therapy. Herein, we report the case of a 44-year-old woman with tFL who relapsed following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and received CAR-T therapy. The patient could not initially undergo CAR-T therapy due to lymphopenia caused by bendamustine exposure, but CAR-T therapy became feasible following allo-HSCT. Although CAR-T therapy using T cells harvested from an allo-HSCT recipient may theoretically cause alloreactivity, the patient did not experience graft versus host disease (GVHD) or serious complications specific to CAR-T therapy, such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), and she has remained in complete response (CR) for >18 months. CAR-T therapy following allo-HSCT for patients with r/r tFL may be a safe and effective treatment option. Allo-HSCT may enhance the efficacy of CAR-T therapy.

Keywords:  Bendamustine; CAR-T therapy; Follicular lymphoma; Hematopoietic stem cell transplantation

DOI:  https://doi.org/10.1007/s00277-024-06150-8
Value Health. 2024 Dec 26. pii: S1098-3015(24)06796-2. [Epub ahead of print]

Cost-Effectiveness of Frontline TKI Strategies for Chronic Myeloid Leukemia Patients: in Pursuit of Treatment-Free Remission and Dose Reduction.

Sanne Jjpm Metsemakers, Rosella Pmg Hermens, Geneviève Icg Ector, Nicole Ma Blijlevens, Tim M Govers.

   OBJECTIVES: Chronic myeloid leukemia (CML) management now includes dose-reduction (DR) and treatment-free remission (TFR). Evaluating cost-effectiveness of lifelong-prescribed expensive tyrosine kinase inhibitors (TKIs) for CML is crucial. Prior cost-effectiveness evaluations state that imatinib is the favorable frontline TKI. Some of these evaluations address TFR, but not DR, nor ageing and second-generation (2G)TKIs upcoming patent-expirations. This study evaluates cost-effectiveness of frontline TKIs for CML patients including these factors.
METHODS: This Markov model evaluates cost-effectiveness of frontline TKIs for newly diagnosed CML patients using 17 health states. Transition probabilities, costs and utilities were derived from literature data. Incremental cost-effectiveness ratios were calculated. Sensitivity analysis and model validation were conducted.
RESULTS: Nilotinib is most effective (20.13 QALYs) and imatinib is least effective (17.25 QALYs) for the model including TFR and DR. Imatinib was favored over dasatinib (89.80%), nilotinib (62.70%), and bosutinib (78.40%), at a WTP of €80,000/QALY. Without TFR and DR, fewer QALYs were generated. For patients at age 70, imatinib has a high probability of being cost-effective compared to dasatinib, nilotinib and bosutinib. With 50% 2GTKI cost reductions, nilotinib is considered cost-effective compared to imatinib (98.40%), dasatinib (94.80%) and bosutinib (68.90%).
CONCLUSIONS: Findings indicate that 2GTKIs are more effective in generating QALYs, including for older (age>70) patients. Given current TKI prices, imatinib remains cost-effective. Including DR and TFR in CML-management generates more QALYs. Cost-reductions from expected 2GTKIs patent-expirations will greatly increase their cost-effectiveness. Results may inform 2GTKIs cost discussions after patent-expiration, potentially broadening global availability. Findings also emphasize the importance of aiming for TFR and DR in CML-management.

Keywords:  Economic evaluation; chronic myeloid leukemia; dose-reduction; healthcare costs; quality of life; treatment-free remission; tyrosine kinase inhibitors

DOI:  https://doi.org/10.1016/j.jval.2024.12.005
Cancer. 2025 Jan 01. 131(1): e35697

Zanubrutinib plus R-CHOP for the treatment of newly diagnosed double-expressor lymphoma: A phase 2 clinical study.

Xia Yin, Qiang He, Dan Liu, Linna Xie, Hui Wang, Chunyan Chen, Chuanli Zhao, Ningning Shan, Shanshan Shi, Haichen Wei, Ji Ma, Ke Lu, Liang Wang, Yan Wang, Lijie Xing, Zengjun Li.

   BACKGROUND: Double-expressor lymphoma (DEL) has a poorer prognosis than other subtypes of diffuse large B-cell lymphoma (DLBCL). This study is a multicenter, prospective, single-arm, phase 2 clinical study initiated by investigators to evaluate the efficacy and safety of combined zanubrutinib with R-CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for patients with DEL (stage II or more), as well as to explore factors related to efficacy preliminarily.
METHODS: From November 2020 to July 2022, 48 newly diagnosed patients were enrolled. All patients received twice-daily oral zanubrutinib (160 mg) for 6 months and standardized R-CHOP regimen for six to eight cycles.
RESULTS: The objective response rate (ORR) was 89.6%, with a complete response rate (CRR) of 83.3%. The median follow-up was 29.3 months. The median progression-free survival (PFS) and overall survival (OS) were not reached. The PFS and OS were 81.25% and 93.75% at 2 years, respectively. Grade ≥3 adverse events (AEs) were reported in 23 of 48 (47.9%) patients. Next-generation sequencing (NGS) results of 33 patients showed that TP53, MYD88, and PIM1 were the most common mutated gene. Multivariate analysis revealed that BCL-6 gene rearrangement was an adverse prognostic factor for both PFS (hazard ratio [HR], 0.247; 95% confidence article [CI], 0.068-0.9; p = .034) and OS (HR, 0.057; 95% CI, 0.006-0.591; p = .016), whereas the number of extranodal involvements also significantly influenced OS (HR, 15.12; 95% CI, 1.07-213.65; p = .044).
CONCLUSIONS: Zanubrutinib in combination with R-CHOP is an effective option for DEL patients, and the toxicity of zanubrutinib is entirely acceptable for patients.

Keywords:  BCL2; BTKi; MYC; double‐expressor lymphoma; zanubrutinib

DOI:  https://doi.org/10.1002/cncr.35697
Transplant Cell Ther. 2024 Dec 31. pii: S2666-6367(24)00841-8. [Epub ahead of print]

Outcomes of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation.

Oren Pasvolsky, Curtis Marcoux, Zhongya Wang, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Naureen Syed, Yosra Aljawai, Hans C Lee, Krina K Patel, Melody R Becnel, Christine Ye, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash.

   BACKGROUND: Patients with multiple myeloma without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous stem-cell transplantation (autoHCT) are limited.
OBJECTIVE: To evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes.
STUDY DESIGN: Single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013-2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization (FISH), defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification.
RESULTS: A total of 1000 SRMM patients were included, with a median age of 61 years (range 25-83), and 61% were male (n=612). The most common induction regimens were bortezomib/lenalidomide/dexamethasone (VRD; n=398, 40%) and carfilzomib/ lenalidomide/dexamethasone (KRD; n=212, 21%), and the majority (87%) received single-agent melphalan as conditioning. After induction and before autoHCT, 16% and 57% achieved ≥ complete response (CR) and ≥ very good partial response (VGPR), respectively. At day 100 post autoHCT, 37% and 77% achieved ≥CR and ≥VGPR, respectively. Sixty-two percent and 89% of patients achieved ≥CR and ≥VGPR as best response post-transplant. A measurable residual disease (MRD) negative response pre- and post-transplantation was achieved in 43% (401/936) and 64% (199/311) of patients, respectively. After a median follow-up of 42.1 months, the median PFS for the entire cohort was 68.3 months (95% CI 60.1-72.1), and the median OS was not reached (95% CI 102.3-not reached). The 5-year PFS and OS rates were 55% and 83%, respectively. In multivariable analysis, achieving MRD-negative CR prior to autoHCT (HR 0.65 [95% CI 0.44 - 0.97], p=0.033) or as best response (0.52 [0.34 - 0.78], p=0.002), and use of post-transplant maintenance (0.69 [0.52 - 0.93], p=0.013) and lenalidomide-based combination maintenance (0.68 [0.48 - 0.96], p=0.030) were associated with improved PFS, whereas use of an induction regimen other than KRD was associated with worse PFS (1.50 [1.04 - 2.17], p=0.031). For OS, post-transplant maintenance (0.48 [0.32 - 0.70], p<0.001) was associated with better survival in multivariable analysis, whereas R-ISS stage III, compared with stage I, (2.34 [1.01 - 5.43], p=0.047) was associated with worse OS.
CONCLUSIONS: Patients with SRMM who received upfront autoHCT had a median PFS of >5.5 years, and median OS was not reached. These results highlight the favorable outcomes with upfront autoHCT for patients with SRMM, serving as a benchmark for future therapeutic approaches in this subgroup of MM patients.

Keywords:  Multiple myeloma; autologous hematopoietic cell transplantation; standard-risk cytogenetics

DOI:  https://doi.org/10.1016/j.jtct.2024.12.023
JAMA Oncol. 2025 Jan 02.

Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial.

Stephen Daw, Peter D Cole, Bradford S Hoppe, David Hodgson, Auke Beishuizen, Nathalie Garnier, Salvatore Buffardi, Maurizio Mascarin, Andrej Lissat, Christine Mauz-Körholz, Jennifer Krajewski, Alev Akyol, Russell Crowe, Bailey Anderson, Yan Xu, Richard A Drachtman, Kara M Kelly, Thierry Leblanc, Paul Harker-Murray.

Importance: Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).
Objective: To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.0 to 30.6 Gy).
Design, Setting, and Participants: CheckMate 744 (R1 cohort) was a phase 2, nonrandomized, single-arm study enrolling children, adolescents, and young adults aged 5 to 30 years with low-risk cHL between September 25, 2017, and December 16, 2020, across the US, Canada, and Europe. Data were analyzed from September 2017 to November 2022.
Exposures: Patients received 4 cycles of nivolumab plus BV induction; patients with complete metabolic response (CMR) received an additional 2 cycles of nivolumab plus BV while patients with suboptimal response received 2 cycles of BV plus bendamustine intensification. Patients with CMR after induction or intensification received ISRT consolidation.
Main Outcomes and Measures: Prespecified coprimary end points were CMR rate (Lugano 2014 classification) any time before ISRT and 3-year event-free survival (EFS) rate, per blinded independent central review (BICR).
Results: Of 28 included patients treated in the low-risk cohort, 18 (64%) were female, and the median (range) age was 17 (6-27) years. At a median (range) follow-up of 31.9 (2.2-55.3) months, CMR per BICR any time before ISRT was 93% (26 of 28; 90% CI, 79.2-98.7; objective response rate [ORR], 100%), and 23 of 28 (82%) achieved CMR per BICR after 4 cycles of nivolumab plus BV (ORR, 96.4%). Kaplan-Meier estimates of EFS and progression-free survival rates at 3 years were 87% (3 of 18; 90% CI, 69.5-94.7) and 95% (1 of 18; 90% CI, 76.7-99.0), respectively. During induction, 22 patients (79%) had treatment-related adverse events, including 7 with grade 3 or 4 adverse events, 2 with anemia, 1 with neutropenia, and 6 with immune-mediated adverse events. Serious adverse events leading to discontinuation occurred in 2 patients.
Conclusions and Relevance: This nonrandomized clinical trial found that for children, adolescents, and young adults with low-risk, relapsed cHL, a transplant-free, risk-adapted, response-based approach with nivolumab plus BV and ISRT offered high CMR rates and high 3-year EFS rate, with a safety profile consistent with that of each agent used.
Trial Registration: ClinicalTrials.gov Identifier: NCT02927769.

DOI: https://doi.org/10.1001/jamaoncol.2024.5627
Ther Adv Hematol. 2024 ;15 20406207241308771

Optimal use of BTK inhibitors in Waldenström's macroglobulinemia: combination or single drug approach?

Eirini Solia, Efstathios Kastritis.

  Waldenström macroglobulinemia is an indolent B-cell lymphoma which although remains incurable, there are a lot of treatment options. Today, Bruton tyrosine kinase inhibitors have a central role in the management of the disease either as monotherapy or combination with other regimens, due to their efficacy, ease of administration, and safety profile. However, there is still active clinical investigation to further increase their efficacy and improve safety profile. Combinations based on BTK inhibitors may offer advantages. Second- and third-generation BTK inhibitors are also evaluated in combinations aiming to improve the depth of response, overcome genetic factors associated with poorer outcomes and reduce toxicity and duration of therapy.

Keywords:  BTK inhibitors; Waldenström’s macroglobulinemia; combination therapy; ibrutinib; monotherapy; sequential treatment

DOI:  https://doi.org/10.1177/20406207241308771
Hematol Oncol. 2025 Jan;43(1): e70031

One-Day Brentuximab-Bendamustine (120 mg/m2) Every 21 Days is a Feasible, Safe and Effective Treatment for Relapsed/Refractory Hodgkin Lymphoma.

H Moatti, P Brice, M-C Laroque, R Di Blasi, J Wencel, T Delory, I Madelaine-Chambrin, C Schmidt-Hieber, O Ravdan, C Thieblemont, L Renaud.

  Brentuximab vedotin (BV)-bendamustine (90 or 120 mg/m2 day 1 and 2) every 28 days is an effective treatment for relapsed/refractory Hodgkin lymphoma (R/R HL) but associated to high toxicity especially for elderly patients. We conducted in St Louis Hospital, Paris, between 2015 and 2021 a retrospective single-center analysis of 44 patients with R/R HL treated with one-day BV-bendamustine (120 mg/m2) every 21 days. Sixteen percent of patients were ≥ 60 years old (yo). Seventy-three percent of patients received total number of cycles without interruption nor adaptation. No patient ≥ 70 yo required treatment interruption. Dose adjustment was necessary for 18% of patients. Infusion-related reaction (36%) occurred always at cycle 2 and was the only cause of treatment interruption. One febrile neutropenia, one non-documented septic shock, one pyelonephritis on transplanted kidney and one COVID complicated by cytopenias were reported. Sixteen percent patients presented a peripheral sensory neuropathy, 7% and 4% respectively grade 3-4 neutropenia and thrombocytopenia. Overall response was 84%, with 73% of complete remission. Median progression-free survival was of 19.8 months (95% CI 13.1-NR) and median overall survival was not reached with a median follow-up of 31 months. We suggest that one-day BV-bendamustine (120 mg/m2) ever 21 days is a safe and feasible treatment for R/R HL especially for elderly patients.

Keywords:  Hodgkin Lymphoma; chemotherapy; refractory; relapse; tolerance

DOI:  https://doi.org/10.1002/hon.70031
Front Oncol. 2024 ;14 1477697

Selinexor in combination with venetoclax and decitabine in patients with refractory myelodysplastic syndrome previously exposed to hypomethylating agents: three case reports.

Yunshuo Xiao, Kun Yang, Qiuying Huang, Changqing Wei, Manlv Wei, Zhili Geng, Hui Wu, Tianhong Zhou, Xialoin Yin, Yali Zhou.

  The management of patients with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) remains a challenge with few reliably effective treatments. Preclinical studies have shown that the inhibition of the nuclear export protein XPO1 causes nuclear accumulation of p53 and disruption of NF-κB signaling; both of which are relevant targets for MDS. Selinexor is an XPO1 inhibitor with demonstrated efficacy in MDS patients. Herein, we report three patients with MDS refractory to HMAs, however, when selinexor and venetoclax were added to the treatment regimen, the patients achieved a complete response and a significant reduction in spleen size. All patients successfully underwent hematopoietic stem cell transplantation. These cases demonstrate that the combination therapy can achieve CR and significant reductions in spleen size, offering a promising therapeutic option for patients with limited treatment choices. Combination therapy would also offer a potential way for patients to bridge to transplantation. Formal evaluations of this regimen in patients with MDS refractory to HMAs may be meaningful.

Keywords:  acute myeloid leukemia; hypomethylating agents; myelodysplastic syndrome; selinexor; venetoclax

DOI:  https://doi.org/10.3389/fonc.2024.1477697
Cancer Med. 2025 Jan;14(1): e70573

Tandem Versus Single Autologous Stem Cell Transplantation for High-Risk Multiple Myeloma in the Era of Novel Agents: A Real-World Study of China.

Xuelin Dou, Juan Ren, Jiangtao Li, Xiaodan Liu, Li Bao, Yuan Chen, Peng Zhao, Yuping Zhong, Nan Peng, Lei Wen, Leqing Cao, Yang Liu, Daoxing Deng, Fengrong Wang, Liru Wang, Hui Liu, Xiaojun Huang, Xiaodong Mo, Jin Lu.

   BACKGROUND: This study compares the efficacy and safety of single autologous stem cell transplantation (ASCT) versus tandem ASCT for multiple myeloma (MM) patients in the era of novel agents.
METHODS: A total of 112 high-risk MM patients were included (single ASCT, (n = 57) or tandem ASCT(n = 55) in this retrospective multicenter study. Responses and outcomes were evaluated.
RESULTS: At 100 days after ASCT1 and ASCT2, 36 (63.2%) versus 45 (81.8%) patients achieved sCR/CR, 16 (28.1%) versus 7 (12.7%) patients achieved VGPR, and 5 (8.8%) versus 1 (1.8%) patient achieved PR, respectively, in the single and tandem ASCT cohorts. The 3-year cumulative incidence of non-relapse mortality and disease progression was 0% versus 7.3% (p = 0.083), and 45.8% versus 25.8% (p = 0.039), respectively, for the single and tandem ASCT cohort. The tandem ASCT cohort showed a trend of better 3-year probability of PFS (58.1% vs. 64.7%, p = 0.064) compared with the single ASCT cohort. In multivariate analysis, ultra high-risk and achieving<VGPR response after ASCT1 were associated with an inferior PFS. Ultra high-risk was also associated with an inferior OS.
CONCLUSIONS: Tandem ASCT demonstrated improved outcomes compared to single ASCT in high-risk MM patients receiving triplet or quadruplet induction and maintenance therapy. However, patients with ultra high-risk cytogenetics may require innovative therapeutic approaches, as tendem ASCT does not overcome their adverse prognosis.

Keywords:  autologous stem cell transplant; multiple myeloma; tandem

DOI:  https://doi.org/10.1002/cam4.70573
Am J Case Rep. 2025 Jan 03. 26 e945435

Successful Treatment of a Patient Presenting with Simultaneous Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma: A Case Report.

Jungmin Lee, Man Hoon Han, Dong Won Baek.

BACKGROUND Simultaneously occuring diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL) is extremely rare. Generally, patients with CD20-positive DLBCL receive rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone (R-CHOP) regimen, while those with HL receive brentuximab vedotin, doxorubicin, vinblastine, dacarbazine (A-AVD) regimen as first-line therapy. Establishing a strategy for treating both lymphoma subtypes concurrently is thus very difficult. We report successful treatment of a patient simultaneously diagnosed with advanced DLBCL and HL. CASE REPORT A 20-year-old man visited the Hematology Department of Kyungpook National University Hospital after the diagnosis of germinal center B-cell DLBCL in the kidney and HL (nodular sclerosis type) in the neck lymph node. His DLBCL was classified as Ann Arbor stage IV with an International Prognostic Index score of 4, a high-risk group. Six cycles of R-CHOP therapy were planned, and central nervous system prophylaxis with intrathecalmethotrexate was added because of the high-risk features of central nervous system involvement. After completing 6 cycles of chemotherapy, without significant adverse events (Deauville score of 1), complete remission was confirmed. Then, the patient decided to undergo consolidative autologous stem cell transplantation (auto-SCT). He received busulfan, cyclophosphamide, and etoposide conditioning regimen, after which auto-SCT was conducted in April 2021. After auto-SCT, the patient was undergoing regular check-ups and doing well, without obvious disease relapse or specific symptoms. He maintained a disease-free status for 40 months to date. CONCLUSIONS Our case showed that R-CHOP regimen was effective not only for DLBCL but also for HL. Notably, consolidative upfront auto-SCT should be considered for a deeper response.

DOI: https://doi.org/10.12659/AJCR.945435
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Dec;32(6): 1676-1681

[Efficacy and Safety of Flumatinib and Imatinib as First-line Treatments for Newly-diagnosed Chronic Myeloid Leukemia in Chronic Phase: A Real-world Study].

Liang Zhang, Hong Deng, Yu Liu, Tai-Ran Chen, Mei-Jiao Huang, Hong-Yan Wang, Xing-Li Zou.

   OBJECTIVE: To compare the efficacy and safety of flumatinib (FM) and imatinib (IM) as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) in real world.
METHODS: A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed. Among them, 32 cases received FM as first-line treatment, and 52 cases received IM. Molecular response (MR), disease progression, survival and incidence of adverse events (AEs) were compared between the two groups.
RESULTS: At 3 months of treatment, the incidences of early molecular response (EMR), MR2.0 and MR3.0 were 96.7%, 70.0% and 20.0% in FM group, respectively, which were significantly higher than 77.1%, 29.2% and 0 in IM group (all P < 0.05). At 6, 9 and 12 months of treatment, the incidences of major molecular response (MMR) in FM group were 68.2%, 85.7% and 90.0%, respectively, which were significantly higher than 22.9%, 34.0% and 51.1% in IM group (all P < 0.01). The median time to achieve MMR in FM group was 6(6-9) months, which was significantly shorter than 18(12-22) months in IM group (P < 0.001). The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100% and 68.8%, respectively, while in IM group were 98.1% and 55.8%. There were no significant differences between the two groups ( P >0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21.9%, which was slightly lower than 25.0% in IM group, but the difference was not significant ( P >0.05).
CONCLUSION: In real clinical practice, FM as first-line treatment achieves MMR earlier than IM, and exhibits good safety profile in newly-diagnosed CML-CP patients, which potentially leads to improved long-term survival and treatment-free remission.

Keywords:   chronic myeloid leukemia; flumatinib; imatinib; efficacy; safety

DOI:  https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.06.007
Leuk Lymphoma. 2025 Jan 02. 1-8

Nodular lymphocyte-predominant Hodgkin lymphoma revisited: current management strategies and future perspectives.

Dennis A Eichenauer, Peter Borchmann.

  Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. As some characteristics of NLPHL resemble B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as alternative name. Unlike classical HL (cHL), NLPHL is mostly diagnosed in early stages. The clinical course is usually indolent. Overall, NLPHL patients have an excellent prognosis and the majority experiences long-term survival. Except for stage IA disease which is sufficiently treated with radiotherapy alone, treatment of newly diagnosed NLPHL is often very similar to cHL. However, activity has also been demonstrated for rituximab-containing protocols applied in B-NHL. Second-line treatment is chosen individually and mostly less intensive than in cHL. Chimeric antigen receptor T-cell therapy and bispecific antibodies may be part of future treatment strategies for NLPHL. This review aims at summarizing recent data on treatment approaches and discussing future perspectives in NLPHL.

Keywords:  LP-IPS; Nodular lymphocyte-predominant Hodgkin lymphoma; histopathological growth pattern; novel approaches; risk groups; treatment

DOI:  https://doi.org/10.1080/10428194.2024.2447886
Cureus. 2024 Dec;16(12): e75022

A Single-Center Experience: Integrated Management in Primary Central Nervous System Lymphoma.

Justin M Kalka, Alexander M Kravets, Bartosz Sokol.

  The present study reports a single-center experience conducted at Józef Struś Multispecialty City Hospital in Poznań, Poland, in diagnosing and treating two patients with primary central nervous system lymphoma (PCNSL), one immunocompetent and one immunodeficient (AIDS). PCNSL is an extremely rare neoplasm with a poor prognosis and non-specific treatment on the basis of immunocompetency. Standard treatment consists of high-dose methotrexate (HD-MTX) being the background of a multimodal therapy, including other chemotherapeutic agents with and without radiation. To our knowledge, no alteration in management exists in immunocompromised individuals and so patients are subject to standard treatment options. Differences in patient management due to immunocompetency may necessitate separate protocols. The immunocompetent patient followed a more typical course, while the immunodeficient patient required balancing lymphoma treatment with the risks of opportunistic infections and drug interactions. These cases underscore the importance of tailored therapeutic approaches based on immune competency, aiming to improve outcomes for PCNSL.

Keywords:  awake craniotomy; immunocompetence; neurosurgery; neurosurgical oncology; primary central nervous system lymphoma

DOI:  https://doi.org/10.7759/cureus.75022
Exp Hematol Oncol. 2025 Jan 02. 14(1): 1

Safety and efficacy of CD33-targeted CAR-NK cell therapy for relapsed/refractory AML: preclinical evaluation and phase I trial.

Ruihao Huang, Xiaoqi Wang, Hongju Yan, Xu Tan, Yingying Ma, Maihong Wang, Xiao Han, Jia Liu, Li Gao, Lei Gao, Guangjun Jing, Cheng Zhang, Qin Wen, Xi Zhang.

   BACKGROUND: Due to the lack of effective treatment options, the prognosis of patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor. Although chimeric antigen receptor (CAR)-T-cell therapy has shown promising effects in acute lymphoblastic leukemia (ALL) and lymphoma, its application in R/R AML is limited by "off-target" effects, which lead to severe bone marrow suppression and limit its clinical application. CAR-natural killer (NK) cells not only exhibit antitumor effects but also demonstrate increased safety and universality. We have developed a new CAR construct that targets CD33 and modified NK cells, specifically eliminating AML cells while reducing severe side effects on stem cells.
METHODS: The CD33-targeting domain was selected by CAR-T cells, and this optimized CAR construct was subsequently transduced into umbilical cord-derived NK cells via a retroviral vector. Preclinical efficacy and safety studies were conducted both in vitro and in vivo. Ten eligible patients with R/R AML aged 18-65 years who received one or more infusions of anti-CD33 CAR-NK cells following the preconditioning regimen were enrolled. We assessed the response rates and treatment-related side effects post-infusion, while also documenting the long-term efficacy of the therapy.
RESULTS: The CD33 sequence was selected on the basis of its antitumor efficacy and safety in CAR-T-cell studies conducted both in vitro and in vivo. CD33 CAR-NK cells demonstrated efficacy comparable to that of CD33 CAR-T cells but showed limited toxicity to hematopoietic stem cells (HSCs). Ten patients, with a median of five prior lines of treatment, completed the efficacy evaluation (range, 3-8). No grade 3-4 adverse events were observed, except bone marrow suppression, which was relieved within one month. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) were reported following CAR-NK cell infusion. Only one patient experienced grade 2 cytokine release syndrome (CRS) and presented with persistent fever. By day 28, six of ten patients had achieved minimal residual disease (MRD)-negative complete remission.
CONCLUSIONS: Our preclinical and clinical data demonstrated the primary efficacy and safety of CD33 CAR-NK cells for patients with R/R AML. Expanded samples and longer follow-up periods are needed to provide further efficacy data.
TRIAL REGISTRATION: NCT05008575 ( https://clinicaltrials.gov/study/NCT05008575 ).

Keywords:  CAR-NK; CD33; R/R AML

DOI:  https://doi.org/10.1186/s40164-024-00592-6
Int J Biol Macromol. 2024 Dec 26. pii: S0141-8130(24)09997-5. [Epub ahead of print] 139186

Antisense oligonucleotides-based approaches for the treatment of multiple myeloma.

Madalina Oprea, Mariana Ionita.

  Multiple myeloma (MM), a hematological malignancy which affects the monoclonal plasma cells in the bone marrow, is in rising incidence around the world, accounting for approximately 2 % of newly diagnosed cancer cases in the US, Australia, and Western Europe. Despite the progress made in the last few years in the available therapeutic options (e.g. proteasome inhibitors, immunomodulatory drugs, tumor cell-targeting monoclonal antibodies, autologous stem cell transplantation, etc.), multiple myeloma is still regarded as incurable, and the prognosis for most patients is poor, as the disease becomes refractory to treatment throughout time. Antisense oligonucleotides (ASOs), designed to be complementary to selected messenger RNA (mRNA) sequences of specific genes involved in the pathogenesis of multiple myeloma (e.g. Bcl-2, Mcl-1, STAT3, IRF4, IL6, ILF2, HK2, c-MYC, etc.), represent a promising alternative to conventional treatments, and can be tailored according to the individual requirements of each patient. The main goal of antisense therapy for multiple myeloma consists in silencing the specific genes participating in the proliferation and survival of tumor cells via RNA cleavage or RNA blockage, thus preventing mRNA interactions with ribosomes and altering the process of protein translation. So far, pre-clinical and clinical studies showed promising results when Bcl-2 (Genasense), Mcl-1 (ISIS2048), STAT3 (ISIS345794) and IRF4 (ION251) were targeted using ASOs-based formulations. However, FDA approval has not been obtained yet for these products, mainly due to ethical and financial issues posed by customized therapies and insufficient information regarding their long-term toxicity. This review aims to provide a comprehensive insight into antisense oligonucleotides-based therapies, their potential chemical modifications, the mechanisms involved in ASOs-mediated gene silencing, potential systems for ASOs delivery, and the applications of ASOs in the treatment of multiple myeloma. The relevant genetic targets in ASOs-based MM therapies were described, and the research results obtained in the studies conducted so far were analyzed, with a focus on the ASOs formulations that were already included in clinical trials. In the end, current challenges, and future perspectives of antisense therapy for MM were also discussed.

Keywords:  Controlled delivery; DNA nanostructures; Gene therapy

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139186