bims-hemali 2025-03-09 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–03–09
nine papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

[Efficacy of chemo-free regimen in treatment of six patients with treatment-naive Philadelphia chromosome-positive mixed phenotype acute leukemia].
Zanubrutinib plus Ixazomib and Dexamethasone in newly diagnosed symptomatic Waldenström macroglobulinemia:a phase II study.
Matching-adjusted indirect comparison of efficacy and safety of lisocabtagene maraleucel and mosunetuzumab for the treatment of third-line or later relapsed or refractory follicular lymphoma.
Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed Refractory Multiple Myeloma.
Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG).
Long-term outcomes with single-agent BRAF inhibitor therapy in Erdheim-Chester disease.
Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations.
Targeting of PIM Kinases Shows Single Agent Efficacy and Synergizes With BCL2 Inhibitors in Diffuse Large B Cell Lymphoma of the ABC Subtype.
68Ga-Pentixafor PET/CT-Based Response Evaluation and its Prognostic Value in Multiple Myeloma: Comparison With IMWG and 18F-FDG-Based Response.

Zhonghua Yi Xue Za Zhi. 2025 Mar 04. 105(9): 708-712

[Efficacy of chemo-free regimen in treatment of six patients with treatment-naive Philadelphia chromosome-positive mixed phenotype acute leukemia].

Y Zhang, Y Fan, M M Xu, Y Q Tu, M Q Xiang, H Y Qiu, S L Xue, X W Tang, S N Chen, D P Wu, J Chen.

To investigate the efficacy of chemo-free regimen in treatment of patients with treatment-naive Philadelphia chromosome positive mixed phenotype acute leukemia(Ph+MPAL). The clinical data of patients with newly treated Ph+MPAL who received venetoclax (VEN), azacytidine (AZA) and tyrosine kinase inhibitors (TKIs) in the First Affiliated Hospital of Soochow University from July 1, 2021 to October 31, 2023 were retrospectively included. The last follow-up date was December 1, 2024. The complete remission/complete remission with incomplete blood count recovery (CR/CRi), measurable residual disease (MRD), survival and safety were analyzed. A total of 6 patients were included, with 1 male and 5 females, aged 40 (25-52) years. The peripheral white blood count at diagnosis was 191.4 (13.6-344.0)×109/L. All 6 patients had mixed expression of B lineage and myeloid lineage. Philadelphia chromosome was detected in 5 patients, and 3 of them had additional chromosomal abnormalities. All 6 patients achieved response after 1 cycle induction therapy, including 3 patients who achieved CR and 3 patients who achieved CRi. And all 6 patients attained bone marrow MRD negativity. After treatment of 1.5 (0.4-5.9) months, 6 patients achieved molecular remission (MMR). Tow patients experienced recurrence. Five patients received allogeneic hematopoietic stem cell transplantation. The follow-up time was 31.4 (13.1-40.6) months, and all 6 patients were in disease-free survival. Severe adverse events mainly included hematological toxicity and sepsis, and no treatment-related deaths occurred. The VEN+AZA+TKIs chemo-free regimen has good efficacy in treating newly diagnosed Ph+MPAL patients.

DOI: https://doi.org/10.3760/cma.j.cn112137-20241029-02423
Clin Cancer Res. 2025 Mar 07.

Zanubrutinib plus Ixazomib and Dexamethasone in newly diagnosed symptomatic Waldenström macroglobulinemia:a phase II study.

Wenjie Xiong, Yuting Yan, Tingyu Wang, Weiwei Sui, Ying Yu, Tengteng Yu, Rui Lyu, Yi Wang, Wei Liu, Huimin Liu, Gang An, Yan Xu, Wenyang Huang, Dehui Zou, Lugui Qiu, Shuhua Yi.

PURPOSE: Waldenström macroglobulinemia (WM) is a rare type of lymphoma, with no optimal treatment. BTK inhibitor have shown promising outcomes, yet achieving deep remission (VGPR or CR) remains challenging and time-limited therapy with proteasome-inhibition has not been reported. We conducted a phase 2 clinical trial (NCT04463953) to evaluate the efficacy and safety of combining zanubrutinib, ixazomib and dexamethasone (ZID) in newly diagnosed WM patients.
PATIENTS AND METHODS: 27 patients were enrolled in the study. Patients received ZID induction therapy for up to six 28-days' cycles, followed by consolidation therapy up to total 24 cycles. The primary endpoint was the deep remission rate.
RESULTS: Overall, 24 of 27 enrolled patients completed induction treatment. One patient (4.2%) achieved CR. 10 patients (41.6%) achieved VGPR. The overall, major and deep remission rates were 100%, 95.8% and 45.8%, respectively. The median time to response was 2 months (range, 1-5). Five of 22 patients had CXCR4 mutation, with no disparity in the deep remission between the patients with/without CXCR4 mutation (40% vs 50%, P=0.594). The median abnormal lymphocyte (7.6% vs 1.6%, P =0.0019) and plasma cells (0.28% to 0.02%, P =0.0306) in bone marrow were significantly reduced after treatment. With a median follow-up of 30.9 months (range, 15-42). The estimated median PFS and OS were 40 months (95% CI:35.5-44.5) and not reached, respectively, with no difference in patients with/without CXCR4mutations. The most common AE was hematological toxicity.
CONCLUSION: ZID regimen might offer deep remission and provided a time-limited BTKi therarpy in WM patients<SPAN style="font-weight: 400;">. </SPAN>.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-3490
Exp Hematol Oncol. 2025 Mar 05. 14(1): 30

Matching-adjusted indirect comparison of efficacy and safety of lisocabtagene maraleucel and mosunetuzumab for the treatment of third-line or later relapsed or refractory follicular lymphoma.

Loretta J Nastoupil, Ashley Bonner, Pearl Wang, Lamees Almuallem, Jigar Desai, Thalia Farazi, Jinender Kumar, Saurabh Dahiya.

   BACKGROUND: The treatment landscape for relapsed or refractory (R/R) follicular lymphoma (FL) has changed with the introduction of anti-CD19 chimeric antigen receptor T-cell therapies, including lisocabtagene maraleucel (liso-cel) and CD20 × CD3 bispecific T-cell-engaging monoclonal antibodies such as mosunetuzumab. Liso-cel and mosunetuzumab have demonstrated positive benefit-risk profiles for third-line or later (3L+) treatment of patients with R/R FL and are approved treatments for these patients. In the absence of a prospective, randomized study, we conducted an unanchored matching-adjusted indirect comparison (MAIC) to assess the efficacy and safety of liso-cel and mosunetuzumab for 3L+ treatment in patients with R/R FL.
METHODS: Unanchored MAICs were performed to estimate relative treatment effects between TRANSCEND FL (NCT04245839) and GO29781 (NCT02500407). For TRANSCEND FL, the leukapheresis set (N = 114) was used for primary comparisons of the following efficacy endpoints: objective response rate (ORR), complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS). The treated set (N = 107) was used for comparisons of the following safety endpoints: cytokine release syndrome (CRS), neurological events (NE), serious infections, and use of corticosteroids or tocilizumab for CRS. Sensitivity analyses were conducted for efficacy using the TRANSCEND FL treated efficacy set (N = 101).
RESULTS: After adjustment, liso-cel was associated with higher ORR (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.48‒9.67]) and CR rate (OR = 6.46, 95% CI 2.85‒14.65), and improved DOR (hazard ratio [HR] = 0.45, 95% CI 0.26‒0.77) and PFS (HR = 0.28, 95% CI 0.16‒0.49) compared with mosunetuzumab. Results remained consistent across sensitivity analyses. Liso-cel had a lower incidence of grade ≥ 3 CRS (OR = 0.45, 95% CI 0.04‒5.13), grade 3‒4 serious infections (OR = 0.35, 95% CI 0.12‒1.03), and corticosteroid use for CRS management (OR = 0.14, 95% CI 0.03‒0.65); however, liso-cel exhibited higher incidence of any-grade CRS (OR = 1.86, 95% CI 1.01‒3.43), any-grade NEs (OR = 2.16, 95% CI 0.72‒6.44), and tocilizumab use for CRS management (OR = 2.27, 95% CI 0.86‒5.99).
CONCLUSIONS: Findings highlight a potential positive benefit-risk profile of liso-cel over mosunetuzumab as a 3L+ treatment for R/R FL.

Keywords:  CAR T-cell therapy; CD20 × CD3 bispecific T-cell–engaging monoclonal antibodies; Indirect treatment comparison; Lisocabtagene maraleucel; Matching-adjusted indirect comparison; Mosunetuzumab

DOI:  https://doi.org/10.1186/s40164-025-00610-1
Niger J Clin Pract. 2024 Dec 01. 27(12): 1405-1409

Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed Refractory Multiple Myeloma.

Hba Öztürk, A A Dikyar, Z A Yeğin, L A Kaynar, F Can, Z N Özkurt.

OBJECTIVES: Allo-Hematopoietic Stem Cell Transplantation (HSCT) offers a curative option for relapsed and refractory multiple myeloma in younger aged and fit patients with high-risk cytogenetic properties.
MATERIAL AND METHODS: This study retrospectively enrolled the medical data of 30 patients who had undergone allogeneic stem cell transplantation at the Gazi University Adult Stem Cell Transplant Unit between 2005 and 2020.
RESULTS: Before allo-SCT, 6 (20.0%) patients were in complete remission; 8 (26.6%) had a partial response; 14 (46.6%) had progressive disease, and 2 (6.6%) had stable disease. Overall survival (OS) at 1, 2, 3, and 5 years post-transplant were 45%, 36.3%, 31.7%, and 22.7%, respectively; transplant-related mortality (TRM) was 25.0% at 100 days. While the 5-year OS was 11.7% in the group with less than PR according to the pre-transplant disease status, it was found to be statistically significant as 45.8% in the group with CR or PR (P = 0.001). TRM was significantly higher in patients with less than PR compared has CR or PR at pre-transplantation (100% vs. 43.7% P = 0.01). Like these findings, PFS was shorter in patients with less than PR compared has CR or PR at pre-transplantation (6.2 vs. 77.1 months, P = 0.01).
CONCLUSIONS: We found longer OS and PFS in patients with a complete response before allo-SCT. This shows that the depth of response before allogeneic stem cell transplantation is effective on 100-day TRM in multiple myeloma patients. Allo-HSCT may be a therapeutic option in MM patients who relapse/refractory after auto-SCT, particularly after achieving the least partial response.

DOI: https://doi.org/10.4103/njcp.njcp_107_24
Eur J Haematol. 2025 Mar 07.

Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG).

Koji Nagafuji, Yoshikiyo Ito, Toshihiro Miyamoto, Tetsuya Eto, Tomohiko Kamimura, Koji Kato, Yasuhiko Miyazaki, Atsuhi Wake, Kentaro Kohno, Ken Takase, Yutaka Imamura, Naoyuki Uchida, Kazuki Tanimoto, Noriaki Kawano, Toshiro Kurokawa, Yukio Kondo, Tomoaki Fujisaki, Junichi Tsukada, Koji Yonemoto, Koichi Akashi.

   AIM: To assess the efficacy of continuous dasatinib in improving outcomes for adult patients with BCR::ABL1 ALL.
METHODS: The prospective, multicenter ALL/MRD2014 trial introduced a modified protocol compared to the MRD2008 trial, incorporating continuous dasatinib use and reduced chemotherapy intensity.
RESULTS: Among the 164 adult ALL patients enrolled (2014-2019), 61 were Philadelphia-positive (Ph+) (median age 50 years; 38 males, 23 females). Post-induction, 96.7% achieved complete remission (CR). The 3-year event-free survival (EFS) and overall survival (OS) were 51% and 76%, respectively. Patients undergoing allo-HSCT in CR1 had improved outcomes, with a 3-year EFS of 64% and OS of 87%. MRD-negative patients before transplantation exhibited superior survival (EFS: 71% vs. 29%; OS: 94% vs. 57%). Comparison with the MRD2008 trial revealed similar outcomes, with the MRD2014 trial achieving a 3-year EFS of 51% and OS of 76% vs. 52% and 84% in MRD2008. Although not statistically significant, the MRD2014 trial showed trends of increased relapse (CIR: 39% vs. 26%, p = 0.305) and reduced non-relapse mortality (NRM: 10% vs. 21%, p = 0.181).
CONCLUSION: The ALL/MRD2014 trial underscores the importance of MRD status and allo-HSCT in Ph+ ALL. Continuous dasatinib-based regimens offer favorable outcomes in MRD-negative patients.
TRIAL REGISTRATION: This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000012382.

Keywords:   BCR::ABL1 ; Philadelphia chromosome; acute lymphoblastic leukemia; dasatinib; tyrosine kinase inhibitor

DOI:  https://doi.org/10.1111/ejh.14407
Blood. 2025 Mar 07. pii: blood.2024028032. [Epub ahead of print]

Long-term outcomes with single-agent BRAF inhibitor therapy in Erdheim-Chester disease.

Gaurav Goyal, Anne S Reiner, Dana Bossert, Allison M Sigler, Mario E Lacouture, Veronica Rotemberg, Jasmine H Francis, Ronald S Go, Raajit K Rampal, Eli L Diamond.

Among 64 patients with Erdheim-Chester disease treated with a BRAF-inhibitor (median follow up 4 years), we found high response rates (85%) but frequent discontinuations (61%), primarily due to adverse events. Additionally, patients experienced persistently poor health-related quality of life.

DOI: https://doi.org/10.1182/blood.2024028032
Leukemia. 2025 Mar 05.

Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations.

Frédéric Millot, Mirella Ampatzidou, Nirmalya Roy Moulik, Sanjay Tewari, Alaa Elhaddad, Mahmoud Hammad, Herbert Pichler, Thomas Lion, Athanasios Tragiannidis, Haruko Shima, Wenbin An, Wenyu Yang, Axel Karow, Roula Farah, Maaike Luesink, Michael Dworzak, Stephanie Sembill, Barbara De Moerloose, Petr Sedlacek, Kirk R Schultz, Krzysztof Kalwak, Birgitta Versluys, Uma Athale, Nobuko Hijiya, Markus Metzler, Meinolf Suttorp.

The treatment strategy for children and adolescents with chronic myeloid leukemia in the chronic phase (CML-CP) has evolved from allogeneic hematopoietic stem cell transplantation (HSCT) to tyrosine kinase inhibitors (TKIs). With the advent of next-generation TKIs and new targeted therapies in the CML field, an international pediatric CML expert panel provides recommendations based on the medical literature (including previous pediatric guidelines), national standards, and treatment principles used in adults with CML-CP. Recommendations include diagnosis of the disease and details on managing the initial steps of care of children and adolescents with newly diagnosed CML-CP, including complications such as leukostasis. The treatment recommendations are based on the initiation of therapy with a first- or second-generation TKI according to the allocated European Treatment and Outcome Study (EUTOS) long-term survival score risk group of the patient. The subsequent steps are based on the results of recommended monitoring which can justify a switch to another TKI or a drug in development if there is resistance or toxicity. The panel also provides recommendations regarding the discontinuation criteria for TKIs in children and adolescents in sustained deep molecular response. Allogeneic HSCT is not recommended as the first-line of treatment for children with CML-CP but is to be considered in case of progression to the advanced phase or failure of several lines of treatment. The present treatment and management recommendations are intended to provide advice to clinicians in view of optimizing the care and the outcome of children and adolescents with CML-CP.

DOI: https://doi.org/10.1038/s41375-025-02543-4
Hematol Oncol. 2025 Mar;43(2): e70055

Targeting of PIM Kinases Shows Single Agent Efficacy and Synergizes With BCL2 Inhibitors in Diffuse Large B Cell Lymphoma of the ABC Subtype.

Chiara Tarantelli, Omar Kayali, Elisa Civanelli, Luciano Cascione, Afua Adjeiwaa Mensah, Chiara Folloni, Alberto J Arribas, Andrea Rinaldi, Vladimir Cmiljanovic, Patrizia Mondello, Francesco Bertoni.

  The PIM family of serine/threonine kinases (PIM1, PIM2, and PIM3) are involved in the development of cancer and represent promising therapeutic targets. We investigated the therapeutic potential of targeting PIM kinases in diffuse large B-cell lymphoma (DLBCL), particularly the activated B-cell-like (ABC) subtype, using the pan-PIM inhibitor AZD1208. We demonstrated that PIM1 and PIM2 are more highly expressed in ABC- cells than in germinal center B-cell-like (GCB) -DLBCL cells, and that ABC-DLBCL cell lines are more sensitive to PIM inhibition with AZD1208. Transcriptome analysis of ABC-DLBCL cell lines treated with AZD1208 revealed a downregulation of genes involved in NF-κB signaling, a crucial pathway for ABC-DLBCL. We also explored synergistic drug combinations using a high-throughput screen, which identified BCL2 and glutaminase inhibitors as effective partners for AZD1208, particularly in aggressive ABC-DLBCL and double-hit cell lines. The combination of AZD1208 with the clinically available BCL2 inhibitor venetoclax was synergistic in most DLBCL cell lines, and this combination induced apoptosis and reduced levels of AKT and MCL1 proteins. In conclusion, our findings suggested that AZD1208, especially when combined with BCL2 inhibitors like venetoclax, holds promise as a treatment strategy for aggressive lymphomas. These combinations may enable lower doses of PIM inhibitors, leading to increased tolerability and improved anti-tumor activity in clinical settings. The study also highlighted the potential for targeting PIM kinases in combination with other therapies to overcome drug resistance in DLBCL.

Keywords:  bcl2; dlbcl; lymphoma; pim

DOI:  https://doi.org/10.1002/hon.70055
Clin Nucl Med. 2025 Mar 07.

68Ga-Pentixafor PET/CT-Based Response Evaluation and its Prognostic Value in Multiple Myeloma: Comparison With IMWG and 18F-FDG-Based Response.

Harneet Kaur, Suraj Kumar, Ankit Watts, Charanpreet Singh, Man Updesh Singh Sachdeva, Sreejesh Sreedharanunni, Rajender Kumar, Pankaj Malhotra, Baljinder Singh.

PURPOSE: 68Ga-Pentixafor PET/CT targets CXCR4 receptors and provides superior diagnostic accuracy in multiple myeloma (MM) compared with 18F-FDG PET/CT. However, its role in response evaluation remains unexplored. We propose a 68Ga-Pentixafor PET/CT-based response evaluation criterion and evaluate its utility compared with International Myeloma Working Group (IMWG) criteria and 18F-FDG PET/CT-based response.
PATIENTS AND METHODS: In this prospective single-center study, 40 treatment-naive myeloma patients were recruited between February 2021 and April 2023. Both 68Ga-Pentixafor and 18F-FDG PET/CT were performed at baseline and at follow-up (7.2 mo-median). Response to treatment was evaluated using the proposed 68Ga-Pentixafor PET/CT criteria and compared with responses assessed by IMWG and 18F-FDG PET/CT. Progression-free survival (PFS) and overall survival (OS) were analyzed and compared using Kaplan-Meier survival curves.
RESULTS: Among the 40 newly diagnosed MM patients [median age: 56.5 years (IQR 45.25 to 63.75); 24 men], 68Ga-Pentixafor PET/CT was positive in a greater proportion of patients than 18F-FDG PET/CT [90% (36/40) vs. 67.5% (27/40); P=0.02] thus, adequately evaluated response in additional 27.5% (11/40) of cases. Using the proposed criteria for 68Ga-Pentixafor PET/CT, significant differences in PFS were observed across response categories [complete response (CR)-not reached, partial response (PR)-26.2 mo, progressive disease (PD)-15.3 mo; P=0.001]. Among patients achieving ≥very good partial response (VGPR) as per IMWG, those with positive 68Ga-Pentixafor PET/CT had shorter PFS compared with those with negative findings (median PFS: 34.2 mo vs. not reached; P=0.056), whereas no significant difference was noted with 18F-FDG PET/CT (P=0.68). In addition, on follow-up of patients with negative 18F-FDG at the response, those with discordant 68Ga-Pentixafor findings had significantly shorter PFS (17.73 mo vs. not reached; P=0.010) compared with those with concordant negative findings.
CONCLUSIONS: 68Ga-Pentixafor PET/CT offers a more accurate assessment of treatment response and prognosis in MM patients, adding valuable information beyond the IMWG and 18F-FDG PET/CT-based criteria.

DOI: https://doi.org/10.1097/RLU.0000000000005731