bims-hemali 2025-05-04 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–05–04
25 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Lisocabtagene maraleucel for R/R LBCL in patients not intended for HSCT: final results of the phase 2 PILOT study.
Brentuximab Vedotin and Nivolumab for Untreated Patients with Hodgkin Lymphoma: Long-term Results.
Bosutinib for Successful Treatment-Free Remission in Chronic Myeloid Leukemia.
Venetoclax plus modified-intensity Idarubicin and Cytarabine treatment as first-line treatment for newly diagnosed pediatric acute myeloid leukemia.
Management of Adult Acute Lymphoblastic Leukemia: A Review.
Phase-1 study of vamotinib (PF-114), a 3rd generation BCR::ABL1 tyrosine kinase-inhibitor, in chronic myeloid leukaemia.
Prospective phase II trial of first-line rituximab, methotrexate, and orelabrutinib (R-MO) in primary central nervous system lymphoma.
Nivolumab plus ifosfamide, carboplatin, and etoposide are a highly effective first salvage regimen in high-risk relapsed/refractory Hodgkin lymphoma.
Outcomes in Frail Patients Receiving BCMA-directed Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma.
Safety and efficacy of programmed cell death-1 inhibitors in relapsed immune-privileged site lymphoma: A systematic review and meta-analysis.
Successful treatment of myeloid blast phase chronic myelogenous leukemia with the JAK2 V617 F mutation by combination therapy with asciminib and ropeginterferon alfa-2b in an elderly patient.
Pegylated Interferons: Still a Major Player for the Treatment of Myeloproliferative Neoplasms.
Optimizing olverembatinib dose in chronic phase chronic myeloid leukemia.
Clinical outcome of ≥2% circulating tumor cells in newly diagnosed multiple myeloma: insights from a multicenter study.
First-line anti-BCMA CAR-T cell therapy in a fragile patient with biclonal gammopathy and giant plasma cell tumor multiple myeloma with multiple comorbidities: a case report.
Tyrosine kinase inhibitors with blinatumomab versus chemotherapy in Philadelphia-positive acute B-lymphoblastic leukemia.
Emerging treatment approaches for VEXAS syndrome: a systematic review and meta-analysis.
The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma.
Targeting Siglec-Sialic Acid Checkpoint to Reverse Immune Dysfunction Mediated by Plasmacytoid Dendritic Cells in Myeloma.
Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma.
Oncologist-Patient Concordance and Treatment Adherence in Chronic Myeloid Leukemia.
Class struggle in DLBCL.
A case series of oral decitabine-cedazuridine with venetoclax for blastic plasmacytoid dendritic cell neoplasm.
Neuropeptide TIP39 induces autophagy in PTH2 receptor-positive myeloid neoplasms.
Mixed-phenotype acute leukemia revisited: omics lead the way.

Blood Adv. 2025 Apr 30. pii: bloodadvances.2024015262. [Epub ahead of print]

Lisocabtagene maraleucel for R/R LBCL in patients not intended for HSCT: final results of the phase 2 PILOT study.

Alison Sehgal, Daanish Hoda, Peter A Riedell, Nilanjan Ghosh, Mehdi Hamadani, Gerhard C Hildebrandt, John E Godwin, Patrick M Reagan, Nina D Wagner-Johnston, James H Essell, Rajneesh Nath, Scott R Solomon, Rebecca Champion, Edward Licitra, Suzanne Fanning, Neel K Gupta, Victor A Chow, Brenda Yuan, Zhi Yang, Ken Ogasawara, Jerill Thorpe, Leo I Gordon.

We report final analysis results from the PILOT study of lisocabtagene maraleucel (liso-cel) for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Sixty-one adults with R/R LBCL who received 1 prior line of therapy and met ≥1 transplant not intended criterion received liso-cel. Overall response rate (primary end point) was 80%; 54% achieved complete response. After median on-study follow-up of 18.2 months, median duration of response was 23.3 months (95% confidence interval [CI], 6.2‒not reached [NR]). Median progression-free survival (PFS) was 9.0 months (95% CI, 4.2‒NR), median overall survival (OS) was NR (95% CI, 16.3‒NR), and 18-month PFS and OS rates were 43% (95% CI, 30‒55) and 59% (95% CI, 45‒70), respectively. In the treatment-emergent (TE) period (≤90 days after liso-cel administration), 79% had grade ≥3 adverse events (AE), 38% had cytokine release syndrome (2% grade 3; no grade 4/5), 31% had neurological events (5% grade 3; no grade 4/5), and 7% had grade ≥3 infections. Of 57 patients in the post-TE period (≥91 days after liso-cel administration), 18% experienced grade ≥3 AEs; 1 patient had grade ≥3 infections. Thirty patients in the leukapheresis set (n = 74) died, mostly of disease progression (n = 24). In this population with high incidence of high-grade B-cell lymphoma, primary-refractory disease, advanced age, and comorbidities, liso-cel demonstrated durable efficacy and a favorable safety profile, consistent with previous reports. These results support liso-cel as second-line therapy for this underserved population of patients with R/R LBCL not intended for hematopoietic stem cell transplantation. ClinicalTrials.gov: #NCT03483103.

DOI: https://doi.org/10.1182/bloodadvances.2024015262
Blood Adv. 2025 May 01. pii: bloodadvances.2025016470. [Epub ahead of print]

Brentuximab Vedotin and Nivolumab for Untreated Patients with Hodgkin Lymphoma: Long-term Results.

Bruce David Cheson, Nancy L Bartlett, Betsy Knopf, Hun Ju Lee, Ranjana H Advani, Beth Christian, Catherine Sibyl Diefenbach, Tatyana A Feldman, Stephen M Ansell.

BACKGROUND: Whereas major improvements have been made in advanced Hodgkin lymphoma (HL) outcomes of patients > 60 yrs are suboptimal with greater toxicity compared with younger patients. In the first phase II study of BV-nivo in older patients with HL (ACCRU RU0515051, NCT02758717), initial results at a median of 20.2 mo of follow-up. (Cheson et al, Lancet Haem, 11:e808, 2020). Herein we present 5-year follow-up for this study.
METHODS: Eligible pts were either >60 yrs or considered unsuitable for standard chemotherapy because of cardiac, pulmonary or renal dysfunction. Pts received BV at 1∙8 mg/kg (dose cap at 180 mg) and nivo at 3 mg/kg both intravenously every 21 days for 8 cycles. The primary endpoint was overall response rate (ORR).
RESULTS: Updated follow-up data were available for 39 of the original 46 pts still alive. At a median follow-up of 58.5 months (0.45-65.4 mo), the median duration of response was 17.2 mo (11.6-45.2). Twenty-seven (58.7%) patients had progressed with the median progression-free survival of 18.3 mo (12.8-46.3 mo); thus 19 (41.3%) had still not experienced a progression event. Median overall survival was not yet reached with 39 (84.8%) patients still alive.
CONCLUSIONS: BV-nivo is an effective regimen for patients >60 yrs, curing approximately 40% of pts. For those not cured by initial therapy, outcome with subsequent treatment is excellent, suggesting check point inhibitor sensitization, or other factors. Optimization of dose and schedule, and incorporation of other novel agents will result in a successful chemo-free approach for older patients with HL.

DOI: https://doi.org/10.1182/bloodadvances.2025016470
Cancer Med. 2025 May;14(9): e70822

Bosutinib for Successful Treatment-Free Remission in Chronic Myeloid Leukemia.

Yuki Fujioka, Maiko Abumiya, Takaaki Ono, Naoto Takahashi.

   INTRODUCTION AND OBJECTIVE: This study explored the status of patients with chronic myeloid leukemia following the safe discontinuation of frontline or second-line bosutinib treatment. The goal was to assess the long-term outcomes and factors influencing treatment-free remission (TFR) following cessation of bosutinib therapy.
METHODS: The median duration of bosutinib treatment among 16 patients was 48 months. All patients achieved a deep molecular response before bosutinib discontinuation, which was sustained for a median pre-cessation period of 27 months. Patients were monitored for molecular response and clinical outcomes.
RESULTS: After bosutinib discontinuation, the major molecular response was lost in six patients: within 6 months in five patients and at 19 months in one patient. All six patients achieved a major molecular response after at least 3 months of bosutinib re-treatment. Ten patients exhibited successful TFR without loss of major molecular response for a median duration of 48 (16-101) months. Kaplan-Meier analysis revealed a 68.8% treatment-free survival at 12 months. After bosutinib cessation, eight patients developed Grade 1-2 withdrawal syndrome. No differences were observed in the clinical characteristics or bosutinib treatment between patients with TFR at 12 months (TFR group) and those without remission (recurrence group), except for the deep molecular response duration before bosutinib cessation (31 vs. 24 months, p = 0.009). T-cell profiling using flow cytometry revealed a higher percentage of effector memory CD8+ T cells at 1 and 3 months after bosutinib discontinuation in the TFR group than in the recurrence group (p = 0.012 and p = 0.005, respectively).
CONCLUSION: Bosutinib can be safely discontinued under certain conditions, similar to other tyrosine kinase inhibitors. Additionally, T-cell profile analysis before and after bosutinib discontinuation may predict successful TFR.

Keywords:  bosutinib; chronic myeloid leukemia; effector memory CD8+ T cells; effector regulatory T cell; treatment‐free remission

DOI:  https://doi.org/10.1002/cam4.70822
Clin Cancer Res. 2025 Apr 28.

Venetoclax plus modified-intensity Idarubicin and Cytarabine treatment as first-line treatment for newly diagnosed pediatric acute myeloid leukemia.

Shiyuan Wang, Mingyan Jiang, Yaqin Wang, Lixian Chang, Beibei Zhao, Xiaoming Liu, Benquan Qi, Shuchun Wang, Tianfeng Liu, Xiaoyan Zhang, Yumei Chen, Fang Liu, Ye Guo, Xiaojuan Chen, Li Zhang, Yao Zou, Wenyu Yang, Ju Gao, Xiaofan Zhu, Min Ruan.

PURPOSE: Venetoclax (VEN) has shown excellent activity in eliminating acute myeloid leukemia (AML) blasts in preclinical and clinical trials, but clinical data in pediatric newly diagnosed AML (ND-AML) remain limited. We evaluated VEN plus modified-intensity idarubicin and cytarabine chemotherapy (VIA) in childhood ND-AML.
EXPERIMENTAL DESIGN: In an open-label, single-arm, multi-center prospective clinical trial, 65 ND-AML pediatric patients received VIA induction (VEN and modified-intensity cytarabine and idarubicin). Consolidation was guided on response to induction and individualized risk stratification. Primary end point was complete remission (CR) and measurable residual disease (MRD) response rates.
RESULTS: After induction cycle 1, CR and MRD negativity was 90.8% and 78.5%, increasing to 96.8% and 87.3% following induction cycle 2. 28 (43.2%) patients underwent hematopoietic stem cell transplantation (HSCT) without engraftment failure. CBF AML [t(8;21) and inv(16)/t(16;16)] patients achieved a favorable response rate, but the median log10 reduction of transcript levels was suboptimal [-1.7 (cycle 1) and -2.6 (cycle 2) for RUNX1::RUNX1T1, -2.3 and -2.5 for CBFB::MYH11]. Disease relapse was frequently observed in KIT mutation, RUNX1::RUNX1T1 and CBFB::MYH11. The most common grade 3-4 toxicities were hematological toxicities and febrile neutropenia (FN). No treatment-related deaths occurred. With a median follow-up of 15.7 months, the estimated 12-month overall survival and event-free survival was 92.3% (95% CI 86.0-99.8) and 79.1% (95% CI 69.6-90.0). MRD negativity post cycle 1 correlated with superior long-term survival (P < 0.001).
CONCLUSIONS: VIA regimen is highly effective and relatively safe in children with ND-AML, with deep remission and favorable survival outcomes.

DOI: https://doi.org/10.1158/1078-0432.CCR-25-0479
JAMA Oncol. 2025 May 01.

Management of Adult Acute Lymphoblastic Leukemia: A Review.

Hagop Kantarjian, Ibrahim Aldoss, Elias Jabbour.

Importance: Research in acute lymphoblastic leukemia (ALL) is translating into rapid changes in therapy and outcomes. Historically, adult ALL was treated with intensive chemotherapy extending over 2.5 to 3 years. This established tradition, accepted because of the high cure rates in childhood ALL, has been challenged by the development of highly active targeted therapies.
Observation: Treatment modalities, combined with less and shorter chemotherapy durations, have produced better results than chemotherapy. The novel therapies include using the more potent BCR::ABL1 tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome-positive ALL and combining blinatumomab and/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. These have been associated with improved 4-year survival rates of 85% to 90% in Philadelphia chromosome-positive ALL and 80% to 85% in B-cell ALL.
Conclusions and Relevance: The management of ALL is changing rapidly. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. Future research will evaluate CD19, CD20, and CD22 multitargeting antibodies and chimeric antigen receptor T-cell therapies, new antibody formulations, and less intensive/shorter regimens.

DOI: https://doi.org/10.1001/jamaoncol.2025.0613
Ann Hematol. 2025 Apr 29.

Phase-1 study of vamotinib (PF-114), a 3rd generation BCR::ABL1 tyrosine kinase-inhibitor, in chronic myeloid leukaemia.

Anna Turkina, Olga Vinogradova, Elza Lomaia, Evgeniya Shatokhina, Oleg Shukhov, Ekaterina Chelysheva, Dzhariyat Shikhbabaeva, Irina Nemchenko, Anna Petrova, Anastasiya Bykova, Nadiya Siordiya, Vasily Shuvaev, Ilya Mikhailov, Fedor Novikov, Veronika Shulgina, Andreas Hochhaus, Oliver Ottmann, Jorge Cortes, Robert Peter Gale, Ghermes Chilov.

Vamotinib (PF-114) is a 3rd -generation, ATP-competitive oral tyrosine kinase inhibitor (TKI) active against wild-type and mutated BCR::ABL1 isoforms including BCR::ABL1T315I. We present final results of a phase-1 vamotinib dose-escalation study to identify maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) followed by expansion cohorts. 51 subjects with chronic myeloid leukaemia (CML) failing ≥ 1 2nd generation TKI or with BCR::ABL1T315I were enrolled. Subjects received vamotinib, 50-750 mg/d, continuously. Median exposure was 6 months (range, < 1-52 months). Median CML duration pre-study was 10 years (range, < 1-23 years). 27 subjects received ≥ 3 prior TKIs and 16 had BCR::ABL1T315I. The MTD was 600 mg with the Grade-3 psoriasis-like skin toxicity as the DLT. There were no vascular occlusive events nor deviations of ankle-brachial index. Complete haematologic response (CHR) was achieved in 14 of 30 subjects, major cytogenetic response (MCyR) in 14 of 44 subjects, complete cytogenetic response (CCyR) in 10 of 50 and major molecular response (MMR) in 7 of 51 subjects who did not have a CHR, MCyR, CCyR or MMR at enrollment. The best safety/efficacy dose was 300 mg with MCyR achieved in 6 of 7 subjects, CCyR in 5 of 9 and MMR in 4 of 9 subjects who did not have a MCyR, CCyR or MMR at enrollment. 5 of 16 subjects with BCR::ABL1T315I responded including 3 achieving a CHR, 3, a MCyR, and 1,a CCyR. 2 of 5 subjects failing ponatinib achieved a CHR. Vamotinib dose for further phase-3 study is 300 mg/d.

DOI: https://doi.org/10.1007/s00277-025-06239-8
Blood Cancer J. 2025 Apr 29. 15(1): 81

Prospective phase II trial of first-line rituximab, methotrexate, and orelabrutinib (R-MO) in primary central nervous system lymphoma.

Lixia Sheng, Hailing Liu, Xiaohui Zhang, Kaiyang Ding, Jie Ma, Hongling Peng, Xia Zhao, Mei Sun, Wei Shi, Feiyan Zhang, Jianyong Li, Lei Cao, Lei Fan.

The treatment of primary central nervous system lymphoma (PCNSL) is currently limited by the impermeability of the blood-brain barrier. This study aims to assess the efficacy and safety of the R-MO regimen (rituximab, high-dose methotrexate, and orelabrutinib) in the treatment of patients with newly diagnosed PCNSL. A total of 37 patients were enrolled in this prospective, multi-center phase II trial. The post-induction overall response rate (ORR) was 90.3%, and the complete response rate (CRR) was 87.1%. Throughout the trial, the best ORR was 97.1%, and the best CRR was 94.1%. With a median follow-up of 12.6 months, the median progression-free survival (PFS) was not reached, with a 1-year PFS rate of 83.6%, meeting the primary study endpoint. The 1-year overall survival rate was 89.6%. Notably, there was no significant difference in PFS between transplanted and non-transplanted groups (P = 0.226). The most common adverse events were neutropenia, lymphocytopenia, and infections, each occurring in 45.9% of patients. Overall, the addition of orelabrutinib to high-dose methotrexate and rituximab in newly diagnosed PCNSL patients has demonstrated promising outcomes and favorable safety profiles, advocating for the use of this combination therapy as a potential frontline treatment option for PCNSL.

DOI: https://doi.org/10.1038/s41408-025-01278-w
Hemasphere. 2025 May;9(5): e70126

Nivolumab plus ifosfamide, carboplatin, and etoposide are a highly effective first salvage regimen in high-risk relapsed/refractory Hodgkin lymphoma.

Matthew Mei, Joycelynne Palmer, Hun Ju Lee, Iris Isufi, Robert Chen, Ni-Chun Tsai, Saro Armenian, James Godfrey, Joo Y Song, John H Baird, Swetha Thiruvengadam, Yazeed Samara, Jessica Flores, Lacolle Peters, Steven Rosen, Larry Kwak, Stephen J Forman, Alex F Herrera.

Nivolumab is an anti-PD-1 antibody that is effective in patients with relapsed/refractory (RR) classic Hodgkin lymphoma (cHL). We previously showed PET-adapted sequential nivolumab ± ifosfamide, carboplatin, and etoposide (ICE) chemotherapy as the first salvage in RR cHL was a safe and effective bridge to autologous stem cell transplant (ASCT) (cohort A). We then tested a non-PET-adapted schema where all patients received nivolumab + ICE (cohort B). In this study, we present results from cohort B. Patients with high-risk RR cHL after frontline treatment received 240 mg nivolumab followed by 2-3 cycles of NICE (240 mg nivolumab day 1, standard doses of ICE). High-risk disease was defined as having one of the following: primary refractory cHL, relapse within 1 year of completing frontline therapy, B symptoms at relapse, extranodal disease at relapse, or frontline brentuximab vedotin use. PET/CT was performed after nivolumab × 1 and NICE × 2. Responding patients (complete response [CR] or partial response) were intended to proceed to ASCT. The primary endpoint was CR rate per 2014 Lugano classification. A total of 35 patients were enrolled, all of whom were evaluable for safety and efficacy. Overall response rate and CR were 100% and 86%, respectively; 2-year progression-free survival (PFS) and overall survival (OS) were 88% and 100%, respectively. Thirty-two patients proceeded to ASCT directly after NICE; 2-year post-ASCT PFS and OS were 94% and 100%, respectively. Immune-related toxicities were all grades 1-2, and no patient discontinued treatment for toxicity. Nivolumab/NICE is a highly effective salvage regimen and bridges patients effectively to ASCT.

DOI: https://doi.org/10.1002/hem3.70126
Blood Adv. 2025 May 02. pii: bloodadvances.2025015973. [Epub ahead of print]

Outcomes in Frail Patients Receiving BCMA-directed Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma.

Benjamin O Adegbite, Carlyn Rose Tan, Tala Shekarkhand, Ross S Firestone, Eric Matthew Jurgens, Kevin C Miller, Alexander M Lesokhin, Gunjan L Shah, Neha Korde, Sridevi Rajeeve, Heather J Landau, Michael Scordo, Hani Hassoun, Kylee H Maclachlan, Urvi A Shah, Malin L Hultcrantz, Issam S Hamadeh, Andriy Derkach, David Nemirovsky, Sergio A Giralt, Sham Mailankody, Saad Z Usmani, Hamza Hashmi.

In addition to advanced age, patients with relapsed refractory multiple myeloma (RRMM) are often frail with pre-existing comorbidities and poor performance status and have been excluded from clinical trials evaluating bispecific antibodies (BsAb). To evaluate clinical characteristics and outcomes based on frailty, we conducted a single center retrospective study of patients with RRMM who received BCMA-directed BsAb. Frailty was defined using the simplified frailty index based on age, ECOG PS, and Charlson comorbidity index (CCI); non-frail = score 0-1, frail = score ≥2. Of 102 patients analyzed (age range 40 - 88), 40 (39%) were considered frail. The frail group had more patients with age ≥ 70 years (73% vs 29%, p <0.001), ECOG PS ≥ 2 (36% vs 0%, p <0.001), and worse median CCI (2 vs 1, p <0.001). Patients in the frail group experienced similar rates of all grade CRS (58% vs 60%, p= 0.99), ICANS (15% vs 8%, p= 0.44), and TRM (13% vs 21%, p= 0.27) compared to the non-frail group. Best overall response rate (ORR) was 80% (15% sCR/CR, 48% VGPR) in the frail group vs 73% (23% sCR/CR, 31% VGPR) in the non-frail group (p= 0.40). With a median follow-up of 8.6 months (range 3-14), there was no significant difference in median PFS (Not reached vs 11 months, p= 0.051) or OS (37 vs 25 months, p= 0.37) between the frail and non-frail groups, respectively. Hence, BsAb were deemed safe and effective for elderly and frail patients with RRMM.

DOI: https://doi.org/10.1182/bloodadvances.2025015973
PLoS One. 2025 ;20(4): e0319714

Safety and efficacy of programmed cell death-1 inhibitors in relapsed immune-privileged site lymphoma: A systematic review and meta-analysis.

Ekdanai Uawithya, Kamolchanok Kulchutisin, Jiraporn Jitprapaikulsan, Nattawut Leelakanok, Weerapat Owattanapanich.

BACKGROUND: Large B-cell lymphoma of immune-privileged sites (LBCL-IP) is a rare subtype characterized by immune evasion properties. Primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL) are examples of LBCL-IP associated with programmed cell death protein 1 (PD-1). Few studies have investigated the use of PD-1 inhibitors in patients with relapsed PCNSL and PTL.
OBJECTIVE: To conduct a systematic review evaluating the efficacy and safety of PD-1 inhibitors in patients with relapsed PCNSL and PTL.
METHODS: We searched the PubMed, Embase, and Scopus databases for relevant studies. The inclusion criteria focused on adult patients diagnosed with relapsed PCNSL or PTL who were treated with PD-1 inhibitors. We excluded case reports or series with fewer than five participants, review articles, and animal studies. A random-effects model with the DerSimonian‒Laird method analyzed the pooled complete response rate (CRR), partial response rate (PRR), overall response rate (ORR), and progression-free survival (PFS) rate.
RESULTS: Seven studies comprising 127 patients (124 with relapsed PCNSL and 3 with PTL) were included. All patients were treated with either nivolumab or pembrolizumab. The pooled CRR was 42.8% (95% CI, 25.7%‒60.0%; I2 = 75.25%; p < 0.001), indicating high heterogeneity. The pooled PRR was 17.1% (95% CI, 9.5%‒24.7%; I2 = 18.71%; p = 0.287), with nonsignificant heterogeneity. The pooled ORR was 67.1% (95% CI, 44.9%‒89.4%; I2 = 88.64%; p < 0.001), indicating high heterogeneity. The 6-month PFS rate was 34.8% (95% CI, 18.1%‒51.5%; I2 = 27%; p = 0.242), with low heterogeneity. Thirty-eight adverse events were reported. The most common were skin reactions (14 events; 36.8%), fatigue (11 events; 28.9%), and nausea (6 events; 15.8%).
CONCLUSIONS: Our study demonstrates that PD-1 inhibitors show promising efficacy in relapsed PCNSL and PTL, with significant responses observed. The adverse effects were mild, with the most common being skin reactions. Therefore, PD1 inhibitors have the potential to drive advancements in treatment strategies for relapsed PCNSL and PTL.

DOI: https://doi.org/10.1371/journal.pone.0319714
Int J Hematol. 2025 Apr 29.

Successful treatment of myeloid blast phase chronic myelogenous leukemia with the JAK2 V617 F mutation by combination therapy with asciminib and ropeginterferon alfa-2b in an elderly patient.

Satoko Oka, Yuina Akagi, Takaya Mituyoshi, Kazuo Ono.

  The co-occurrence of JAK2 V617F mutations and the BCR::ABL1 translocation in the same patient is rare, and the current standard treatment for aggressive myeloid blast phase chronic myeloid leukemia (CML-myeloid BP) with JAK2 V617F mutations remains inadequate, particularly in transplant-ineligible patients. Asciminib, a first-in-class allosteric inhibitor of BCR::ABL1 kinase that specifically targets the ABL1 myristoyl pocket, has emerged as a novel alternative to standard tyrosine kinase inhibitor (TKI) therapy. Ropeginterferon alfa-2b (ropegIFNα2b) is a novel site-selective, monopegylated recombinant human IFN with long-term safety and efficacy in patients with polycythemia vera (PV). Here, we report a case of successful combination therapy with asciminib and ropegIFNα2b in a patient with CML-myeloid BP who had a long history of PV with JAK2 V617F refractory to induction chemotherapy with several TKIs. The combination of asciminib and ropegIFNα2b is a promising new treatment option for these patients.

Keywords:   BCR::ABL1 ; JAK2 V617 F mutation; Asciminib; Myeloid blast phase chronic myeloid leukemia (CML-myeloid BP); Ropeginterferon alfa-2b

DOI:  https://doi.org/10.1007/s12185-025-03994-2
Am Soc Clin Oncol Educ Book. 2025 Jun;45(3): e473912

Pegylated Interferons: Still a Major Player for the Treatment of Myeloproliferative Neoplasms.

Michael Daunov, Rebecca B Klisovic.

Over the past 35 years, interferons have been explored in various formulations for the management of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), such as essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis, and remain a key tool in caring for patients with these diseases. These agents are excellent cytoreductive agents with high rates of hematologic response, are helpful in symptom management, and have a long track record of safety and manageable toxicities. More recently, they have shown promise in sustaining responses over many years, with associated reductions in driver mutations (JAK2, MPL, CALR) of these diseases, particularly in PV and ET. Since reductions in molecular mutant allele burden have been correlated with several response outcomes such as reductions in both thrombotic risk and disease progression, there is emerging proof that interferons may offer disease-modifying activity. These long-term benefits and their use as the preferred agent in young pregnant women who need cytoreduction make interferons often the first choice in young adult population who harbor a lifetime risk of progression. Looking forward, the prospect of sustained treatment-free responses, like chronic myeloid leukemia after deep molecular response, and normal life expectancy may also be on the frontier. Despite relative rookies such as JAK inhibitors in the MPN landscape, the veteran in the game, interferon, remains a key player.

DOI: https://doi.org/10.1200/EDBK-25-473912
Haematologica. 2025 Apr 30.

Optimizing olverembatinib dose in chronic phase chronic myeloid leukemia.

Xiaoshuai Zhang, Yunfan Yang, Bingcheng Liu, Xin Du, Xiaodong Wang, Huanling Zhu, Lu Yu, Zongru Li, Shasha Zhao, Linhua Yang, Yanping Ma, Li Meng, Yanqing Zhang, Guohui Li, Lijie Yang, Baohong Wang, Xuehong Ran, Jian Huang, Na Gao, Qin Wen, Yan Wen, Yuxia Zhao, Yu Zhu, Yanqiu Han, Zhenfang Liu, Xin Du, Jianyu Weng, Robert Peter Gale, Li Zhou, Yanli Zhang, Qian Jiang.

Optimizing olverembatinib dose in people with chronic phase chronic myeloid leukemia (CML) is important to increase safety without compromising efficacy. We designed a multi-center retrospective study comparing safety and efficacy of olverembatinib between the recommended dose of 40 mg every other day (QOD; N = 216) and a reduced dose of 30 mg QOD (N = 66) in subjects failing other tyrosine kinase-inhibitors (TKIs). The cohorts were similar in baseline co-variates and adjusted for by propensity score matching (PSM). There were no significant differences in cytogenetic and molecular responses, as well as outcomes between the 2 dose cohorts. However, the proportion of subjects receiving the original olverembatinib dose at the last follow-up was significantly higher in the 30 mg cohort (64% [95%Confidence Interval [CI], 53, 75%] versus 44% [37,51%]; p = 0.004). Also, the proportion of subjects receiving a reduced dose or permanently discontinuing because of adverse event was significantly lower in the 30 mg cohort (21% [9, 33%] versus 41% [34, 48%]; p = 0.003). In summary, olverembatinib, 30 mg QOD starting dose is as effective as a 40 mg starting dose but better tolerated in persons with chronic phase CML failing other TKIs.

DOI: https://doi.org/10.3324/haematol.2024.287116
Ann Med. 2025 Dec;57(1): 2496796

Clinical outcome of ≥2% circulating tumor cells in newly diagnosed multiple myeloma: insights from a multicenter study.

Dong Liang, Yurong Yan, Shenrui Bai, Weiling Xu, Qiaoli Wang, Demei Feng, Yuying Bu, Min Zeng, Xiaomiao Nie, Yuan Feng, Xiaoqin Chen, Zhongjun Xia, Yang Liang, Fengyan Jin, Hua Wang.

   PURPOSE: Previous studies have shown that ≥2% circulating tumor cells (CTCs) in multiple myeloma are associated with a prognosis similar to primary plasma cell leukemia. This study aims to examine this ultra-high-risk patient subset and evaluate their clinical outcomes in a real-world clinical setting.
METHODS: We included 1,056 newly diagnosed multiple myeloma patients treated with novel agents. CTCs levels were determined via morphological assessment on peripheral blood smears, using a 2% cutoff to stratify patients into <2% and ≥2% CTCs groups. We then evaluated clinical outcomes across these groups.
RESULTS: Patients with ≥2% CTCs constitute an ultra-high-risk subgroup, with outcomes resembling those of primary plasma cell leukemia. Survival outcomes improved for patients receiving daratumumab-based quadruplet therapy. Single autologous stem cell transplantation (ASCT) partially improved outcomes for patients with ≥2% CTCs. Achieving complete remission (CR) after induction treatment did not confer a better prognosis for this population. Furthermore, one high-risk cytogenetic abnormality (HRA) worsened outcomes in the <2% CTC group, while ≥2 HRA were associated with poorer outcomes in the ≥2% CTC group. Concurrent 1q21+ and other HRA further conferred a worse prognosis. In de novo extramedullary extraosseous (EME) multiple myeloma, defined as patients presenting with soft tissue or visceral plasmacytomas not connected to bone at initial diagnosis, ≥2% CTCs remained a strong predictor of poor prognosis.
CONCLUSION: Our study suggests that patients with ≥2% CTCs represent a distinct ultra-high-risk subgroup in multiple myeloma and warrant separate consideration. VRD, IRD, DVRD, and DRD were reliable choices as frontline therapies for patients with <2% CTCs. Daratumumab-based quadruplet therapy may be a promising option for patients with ≥2% CTCs. Further research should continue to explore this specific aspect in greater depth.

Keywords:  Circulating tumor cells; clinical outcome; multiple myeloma

DOI:  https://doi.org/10.1080/07853890.2025.2496796
Front Immunol. 2025 ;16 1564774

First-line anti-BCMA CAR-T cell therapy in a fragile patient with biclonal gammopathy and giant plasma cell tumor multiple myeloma with multiple comorbidities: a case report.

Yi Fang, Weiwei Lin, Lijing Shen, Beiwen Ni, Minyue Zhang, Yongmei Cai, Yi Zhou, Jian Hou.

   Background: Chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used as an effective therapy against relapsed/refractory multiple myeloma (MM). However, the relapse rates in these patients are still high, which may be related to the poor quality of T cells after multiple chemotherapies. The case reported here demonstrated the effectiveness and safety of first-line anti-BCMA CAR-T cell therapy for high-risk MM patients, even in frailty with multiple comorbidities.
Case presentation: A 75-year-old woman was diagnosed with biclonal gammopathy and high-risk MM with extramedullary mass in the right caput femoris. The patient was fragile with multiple comorbidities, including pneumonia, left lower limb deep venous thrombosis, and epilepsy secondary to cerebral hemorrhage. Considering the patient's fragility and comorbidities, commercial equecabtagene autoleucel, a fully human anti-BCMA CAR-T cells, as first-line CAR-T cell therapy, was proposed and accepted by the patient and her family. After one cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen), she reached very good partial response (VGPR). Then her leukapheresis was performed, and the harvested cells were sent to the manufacturer for preparation. After lymphodepletion was performed using fludarabine and cyclophosphamide (FC) chemotherapy, her equecabtagene autoleucel was transfused. On day 21 after infusion, she achieved stringent complete remission (sCR) with minimal residual disease (MRD) negativity without severe toxicity. The CAR-T cells/CD3+ T cell ratio gradually increased, reaching a maximum of 54.97% on day 14, and gradually decreased, remaining at 0.03% on the 153rd day. The patient received right hip replacement plus pelvic lesion curettage 7 months after CAR-T transfusion due to pain in her right hip, but no MM cells were found in postoperative pathology. Hitherto, her deep remission persisted for 12 months without any maintenance therapy.
Conclusion: First-line anti-BCMA CAR-T cell therapy is effective and safe for high-risk MM patients, even in fragile patients with multiple comorbidities.

Keywords:  biclonal gammopathy; case report; chimeric antigen receptor T cells; first-line therapy; multiple myeloma

DOI:  https://doi.org/10.3389/fimmu.2025.1564774
Int J Cancer. 2025 Apr 30.

Tyrosine kinase inhibitors with blinatumomab versus chemotherapy in Philadelphia-positive acute B-lymphoblastic leukemia.

Sebastian M Stolz, Kevin D Hofer, Wiebke Rösler, Jeremy Deuel, Rahel Schwotzer, Corina Schneidawind, Dominik Schneidawind, Markus G Manz, Max J Rieger.

  Tyrosine kinase inhibitors (TKIs) and blinatumomab have improved outcomes in Philadelphia-positive B-lymphoblastic leukemia (Ph + B-ALL). However, the efficacy of TKI and blinatumomab as a standalone regimen compared to the standard chemotherapy-plus-TKI approach remains uncertain. We conducted a single-center retrospective analysis of 47 patients, including 18 treated with TKI and blinatumomab (de novo: N = 13; relapsed: N = 5) and 29 treated with chemotherapy and TKI. Patients in the blinatumomab cohort were significantly older (median age 65 years vs. 48 years), had higher rates of active central nervous system disease (27.7% vs. 0%) and were less frequently consolidated with allogeneic stem cell transplantation (33% vs. 79%, p < .05). Despite these differences, overall survival (2-year OS: 87% vs. 78%), progression-free survival (PFS: 81% vs. 54%), and non-relapse mortality (NRM: 6.3% vs. 14%) were comparable. Severe treatment-related adverse events were significantly less frequent in the TKI and blinatumomab cohort, with no difference in early molecular complete response rates. Our findings, consistent with published prospective trials, highlight the safety and efficacy of TKI and blinatumomab in managing Ph + B-ALL.

Keywords:  Ph + B‐ALL; TKI; blinatumomab

DOI:  https://doi.org/10.1002/ijc.35468
Ann Hematol. 2025 Apr 27.

Emerging treatment approaches for VEXAS syndrome: a systematic review and meta-analysis.

Berkay Kilic, Efe Sacin, Muhammet Kadir Tanin, Ozgur Can Kilinc, Serdal Ugurlu.

  VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a monogenic autoinflammatory disorder with significant morbidity and mortality. Numerous treatment options including azacitidine, JAK inhibitors, IL-6 inhibitors, anti-IL-1, and anti-TNF agents have been proposed. However, no consensus on optimal treatment algorithm has been reached. This study aims to evaluate the efficacy and safety of medical treatment options through a meta-analysis of existing data to help establish clearer guidelines for managing VEXAS. The study protocol was registered in PROSPERO (CRD42024590134). MEDLINE and EMBASE were screened from inception until March 2025. We included patients with VEXAS syndrome who received treatment with azacitidine, JAK inhibitors, IL-6 inhibitors, anti-IL-1, or anti-TNF agents. The primary outcome was the proportion of complete responders. Partial response and reported adverse events were also evaluated. A total of 16 studies and 367 patients with VEXAS syndrome were included. Concomitant myelodysplastic syndrome (MDS) was reported in 149 (40.6%) patients. Azacitidine treatment resulted in complete and partial response in 67% [95% CI (0.56,0.77)] and in 73% [95% CI (0.64,0.82)] of cases, respectively. JAK inhibitors produced a complete response in 42% [95% CI (0.33,0.52)] and partial response in 79% [95% CI (0.71,0.87)]. IL-6 inhibitors led to a complete response in 24% [95% CI (0.15,0.32)] and partial response in 72% [95% CI (0.64,0.81)]. Adverse events were frequently observed. Azacitidine demonstrated significant efficacy in patients with MDS. JAK inhibitors and IL-6 inhibitors may also be viable treatment options. Prospective clinical trials are needed for further confirmation of the results.

Keywords:  Autoinflammatory diseases; Azacitidine; Biological agents; JAK inhibitors; Myelodyplastic syndrome; VEXAS

DOI:  https://doi.org/10.1007/s00277-025-06382-2
Expert Opin Investig Drugs. 2025 May 01.

The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma.

Harry Hambleton, Chan Y Cheah.

   INTRODUCTION: Follicular Lymphoma (FL) is the most common indolent lymphoma. Patients with advanced stage FL typically respond to therapy, then follow a relapsing/remitting course, with shorter progression-free survival with each subsequent line of therapy. Whilst existing CD-19 directed therapies such as CAR T-cell therapy have shown promising efficacy in the management of relapsed/refractory FL, immune-mediated adverse events, such as cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity (ICANS), are well described. AZD0486 is a fully human bispecific (CD19xCD3) T-cell engager (TCE) that induces T cell-mediated cytotoxicity, but with low affinity binding of CD3, resulting in a reduction in cytokine release.
AREAS COVERED: In this review we describe the key pre-clinical data for AZD0486 and evaluate in detail the available clinical data from the ongoing phase 1 first-in-human study, including safety, efficacy, pharmacokinetics, and future development plans.
EXPERT OPINION: Bispecific TCEs are among the most promising novel therapies in use for the management of relapsed/refractory B-cell lymphomas. AZD0486 results in high complete response rates with low incidence of high grade immune-mediated toxicity compared to alternative TCE therapies. Importantly, it remains active in patients with lymphomas that have lost CD20 expression, an important mechanism of treatment failure following CD20 targeting TCEs.

Keywords:  Bispecific antibody; CD19; CD20; CD3; T-cell engaging antibody; cell therapy; follicular lymphoma; immunotherapy; lymphoma; monoclonal antibody

DOI:  https://doi.org/10.1080/13543784.2025.2500290
Blood Adv. 2025 May 01. pii: bloodadvances.2025015980. [Epub ahead of print]

Targeting Siglec-Sialic Acid Checkpoint to Reverse Immune Dysfunction Mediated by Plasmacytoid Dendritic Cells in Myeloma.

Arghya Ray, Leutz Buon, Xueping Wan, Ting Du, Yan Song, Sindhu C Pillai, Md Abu Musa, Teng Fang, Minxing Wang, Kenneth C Anderson.

DOI: https://doi.org/10.1182/bloodadvances.2025015980
J Clin Oncol. 2025 May 01. 101200JCO2500690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma.

ECHO investigators

BACKGROUND: The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival, but without improvement to overall survival likely due to toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL.METHODS: Patients aged ≥65 years with previously untreated mantle cell lymphoma received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus 6 cycles of bendamustine (90 mg/m2; days 1 and 2) and rituximab (375 mg/m2; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. Primary endpoint was progression-free survival per independent review committee; overall response rate and overall survival were secondary endpoints.RESULTS: In total, 598 patients were randomized, with 299 in each arm. At a median follow-up of 44.9 months, median progression-free survival was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio, 0.73; 95% confidence interval, 0.57 to 0.94; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. Overall survival was not significantly different (hazard ratio, 0.86; 95% confidence interval, 0.65 to 1.13; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively.CONCLUSIONS: Combination of acalabrutinib with bendamustine-rituximab significantly improved progression-free survival. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.

DOI: https://doi.org/10.1200/JCO-25-00690
JAMA Netw Open. 2025 Apr 01. 8(4): e258039

Oncologist-Patient Concordance and Treatment Adherence in Chronic Myeloid Leukemia.

J Felipe Montano-Campos, Erin E Hahn, Eric C Haupt, Jerald Radich, Aasthaa Bansal.

DOI: https://doi.org/10.1001/jamanetworkopen.2025.8039
Blood. 2025 May 01. 145(18): 1967-1969

Class struggle in DLBCL.

Joanna A Krupka, Daniel J Hodson.

DOI: https://doi.org/10.1182/blood.2024027995
Leuk Lymphoma. 2025 Apr 30. 1-4

A case series of oral decitabine-cedazuridine with venetoclax for blastic plasmacytoid dendritic cell neoplasm.

Hannah Goulart, Guillermo Garcia-Manero, Tapan M Kadia, Naval Daver, Courtney D DiNardo, Farhad Ravandi, Muzaffar Qazilbash, Caitlin Rausch, Gabriela Llaurador Caraballo, Sherry Pierce, Naveen Pemmaraju.



Keywords:  Myeloid leukemias and dysplasias; chemotherapeutic approaches; pharmacotherapeutics

DOI:  https://doi.org/10.1080/10428194.2025.2498046
Int J Hematol. 2025 Apr 27.

Neuropeptide TIP39 induces autophagy in PTH2 receptor-positive myeloid neoplasms.

Kento Ono, Hiroto Horiguchi, Satoshi Iyama, Ken Sato, Saori Ibuki-Shimoyama, Shotaro Shirato, Yusuke Sugama, Akari Goto, Masayoshi Kobune.

  Neuropeptides are chemical messengers that are synthesized and released by nerve cells. Studies suggest that neuropeptides released from the nervous system in bone marrow may be involved in the regulation of hematopoiesis and survival of leukemic stem cells (LSC). Parathyroid hormone 2 receptor (PTH2R), a new LSC marker, is expressed on CD34 + leukemic cells. Its ligand, tuberoinfundibular peptide of 39 residues (TIP39), is expressed in the nervous system. However, the role of the TIP39-PTH2R axis in leukemic cells is unclear. We investigated the function of this axis in leukemic cell lines, as well as primary CD34 + myelodysplastic syndrome (MDS) and AML cells. Expression of PTH2R mRNA was higher in primary CD34 + MDS (GSE58831) or CD34 + CD38-AML (GSE24395) cells than in healthy volunteers. TIP39 reduced apoptosis in the leukemic cell lines Kasumi-1 and SKM-1. LC3-II expression was increased after incubation with TIP39, and was augmented in leukemic cell lines treated with lysosome inhibitors. This suggests that TIP39 could induce autophagy. Analysis of a public database (GSE58831) showed that high PTH2R expression was associated with poor overall survival and was an independent prognostic factor in MDS/AML patients. Our results suggest that the TIP39-PTH2R axis is a potential therapeutic target.

Keywords:  Acute myeloid leukemia; Autophagy; Leukemic stem cell; Myelodysplastic syndrome; PTH2R; TIP39

DOI:  https://doi.org/10.1007/s12185-025-03985-3
Blood. 2025 May 01. 145(18): 1969-1971

Mixed-phenotype acute leukemia revisited: omics lead the way.

Lars Bullinger.

DOI: https://doi.org/10.1182/blood.2025028351