bims-hemali 2025-07-06 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–07–06
twenty papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Treatment Free Remission (TFR) in Chronic Phase-Chronic Myeloid Leukemia (CP-CML): Analysis of Predictive Factors and Novel Baseline Scoring System to Predict Molecular Relapse.
CML stem cells and their interactions and adaptations to tyrosine kinase inhibitors.
Artificial intelligence-driven label-free detection of chronic myeloid leukemia cells using ghost cytometry.
Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting.
Outcomes at a single institution with MTR induction and consolidation in the management of primary CNS lymphoma.
Tagraxofusp maintenance post-hematopoietic stem cell transplantation provides long-term survival and manageable safety for a patient with blastic plasmacytoid dendritic cell neoplasm.
Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial.
Chronic myeloid leukemia outcomes according to baseline risk and first-line treatment in real-world settings: Data from the Italian Network/CML Campus.
Asciminib for relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.
Optimising T-cell immunotherapy in patients with multiple myeloma: practical considerations from the European Myeloma Network.
Combination of venetoclax with CHG regimen in refractory/relapsed T-lymphoblastic lymphoma/acute lymphoblastic leukemia: a case series and literature review.
Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies.
Another 1q bites the dust.
Management of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia in a Jehovah's Witness using chemotherapy free regimen: A case report and review of literature.
Functional cure with single agent olutasidenib in relapsed IDH1/NPM1 co-mutated AML.
SRSF2-mutated MDS: bortezomib STAT?
Non- MPL-W515K/L mutations in myeloproliferative neoplasms: insights from two case reports and a review of the literature.
BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma.
BTKi +humanized anti-CD20 for advanced follicular lymphoma: ready for an ALTERNATIVE?
Oral and Intravenous Iron Therapy.

Eur J Haematol. 2025 Jun 30.

Treatment Free Remission (TFR) in Chronic Phase-Chronic Myeloid Leukemia (CP-CML): Analysis of Predictive Factors and Novel Baseline Scoring System to Predict Molecular Relapse.

Alessandro Laganà, Emilia Scalzulli, Ida Carmosino, Maria Laura Bisegna, Claudia Ielo, Daniela Diverio, Maurizio Martelli, Massimo Breccia.

   BACKGROUND: Treatment free remission (TFR) is a key treatment goal in chronic-phase chronic myeloid leukemia (CP-CML) patients with sustained deep molecular response (DMR). While clinical trials report that approximately 40%-50% of such patients can discontinue tyrosine kinase inhibitors (TKIs) without presenting a molecular relapse (MRec), real-world data remain limited. Optimizing patient selection before TKI discontinuation is crucial for CML management and resource allocation.
METHODS: We conducted a single-center retrospective study on CP-CML patients who discontinued TKIs to evaluate the rate and duration of successful TFR and to identify factors predictive of MRec. Eligibility required prior TKI treatment ≥ 3 years, a minimum molecular response (MR) of MR4.0 before discontinuation, and subsequent serial MR monitoring. MRec was defined as the loss of major MR (MMR).
RESULTS: Of the 118 consecutive CP-CML patients, 60.2% were on imatinib and 39.8% on 2G-TKIs before attempting TFR. Median TKI treatment duration was 10.6 years, and median stable DMR duration was 6.1 years. After a median follow-up of 72.5 months, 34 patients (28.8%) had an MRec, and estimated MRec-free survival was 79.7% at 6 months and 69.9% overall. Multivariate analysis identified three factors associated with shorter TFR: High-risk Sokal score (HR 2.93, p = 0.018), stable DMR duration before TKI suspension < 5 years (HR 3.63, p = 0.002), and prior unstable DMR (HR 2.47, p = 0.019). The BASE-TFR score, assigning one point per factor, stratified patients into low-risk, intermediate-risk (HR 4.19, p = 0.009) and high-risk (HR 14.06, p < 0.001) for MRec.
CONCLUSIONS: TFR is feasible in real-world settings. BASE-TFR score may help to better identify candidates for TKI discontinuation in real-life settings.

Keywords:  BASE‐TFR; chronic myeloid leukemia (CML); deep molecular response (DMR); molecular recurrence (MRec); treatment‐free remission (TFR); tyrosine kinase inhibitors (TKIs)

DOI:  https://doi.org/10.1111/ejh.70006
Leuk Lymphoma. 2025 Jul;66(7): 1211-1220

CML stem cells and their interactions and adaptations to tyrosine kinase inhibitors.

Stein-Erik Gullaksen, Maria Omsland, Mathias Brevik, Johanna Letzner, Stine Haugstvedt, Bjørn Tore Gjertsen.

  Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy, driven by the pathognomonic oncogenic fusion protein BCR::ABL1. Tyrosine kinase inhibitors (TKIs) targeting ABL1 have increased the life expectancy of patients with CML to near levels of age-matched healthy individuals. Intriguingly, the response to TKIs varies substantially and is related to observations that CML leukemic stem cells (LSCs) are less sensitive to TKIs. LSC-derived suboptimal response is suggested to explain failing treatment free remission (TFR) in approximately 60% of patients after stopping TKI treatment. Identification of novel and druggable targets on CML LSCs is a possible pathway for increasing TFR. Here we will focus on the role of CML LSCs in initial patient response to TKI therapy, and the possible interactions that LSC may experience in the bone marrow stroma. Adaptation of LSC and stroma is likely to play a central role in the heterogenous responses. Even if overall survival in CML is outstanding, deeper understanding of LSC biology may help more patients to avoid life-long therapy.

Keywords:  Chronic myeloid leukemia; Tyrosine kinase inhibitor; leukemic stem cells; phosphorylation; signaling; tumor micro environment

DOI:  https://doi.org/10.1080/10428194.2025.2466817
Sci Rep. 2025 Jul 01. 15(1): 21046

Artificial intelligence-driven label-free detection of chronic myeloid leukemia cells using ghost cytometry.

Kohjin Suzuki, Naoki Watanabe, Yutaka Tsukune, Tadaaki Inano, Shintaro Kinoshita, Sayuri Tomoda, Kohei Yamada, Yusuke Konishi, Takuya Kuwana, Takeshi Sugiyama, Kenji Fukada, Kazuhiro Yamada, Miki Ando, Tomoiku Takaku.

Early diagnosis and treatment initiation of chronic myeloid leukemia (CML) are considered to increase the rate of deep molecular response. However, the early diagnosis of CML is challenging due to the absence of clinical symptoms and peripheral blood test anomaly, especially at the timing of peripheral white blood cell count is within a normal range. This study explored the possibility of artificial intelligence (AI)-based quantitative detection of CML cells using ghost cytometry (GC) technology. We created pre-trained AI models, using the morphological information data of the peripheral blood leukocytes obtained from patients newly diagnosed with CML and healthy individuals. We applied these models to peripheral blood samples from CML patients after initiating tyrosine kinase inhibitor treatment at various time points, which contains smaller amounts of tumor cells. The AI model accurately detected CML cells and a strong correlation between AI-detected CML cells and actual BCR::ABL1IS mRNA levels was observed. We concluded that the multidimensional morphological information of single cells obtained using GC, combined with machine learning algorithms, enables the quantitative detection of label-free CML cells. Our finding may enable the development of a screening test that can identify early-stage patients with CML before numerical abnormalities appear in blood tests.

DOI: https://doi.org/10.1038/s41598-025-06664-9
Biomark Res. 2025 Jul 01. 13(1): 90

Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting.

Qing Zhang, Yongping Song, Keshu Zhou, Quande Lin.

  Novel agents with innovative mechanisms of action were updated at the latest 2024 ASH Annual Meeting, some featuring first trials in combinations. Advances span new antibodies, bispecific T-cell engagers, next-generation CELMoDs, and agents targeting previously unexplored pathways in relapsed/refractory multiple myeloma. Key updates include: Cevostamab (FcRH5×CD3) demonstrated a 30.2% overall response rate in patients who underwent BCMA-targeted treatment and 60.6% in BCMA-targeted naïve patients;the triple-step dosing strategy reduced cytokine release syndrome. Lisaftoclax (APG-2575, BCL-2 inhibitor) displayed overall response rates ranging from 61.3 to 100% and ≥ VGPR rates of 32.3-100%, supporting enhanced response depth with favorable safety in combination regimens. Inobrodib (CCS1477, p300/CBP inhibitor) plus lenalidomide achieved a 71% overall response rate in pomalidomide-refractory patients, marking the first oral epigenetic modulator to reverse immunomodulatory drug resistance. Elranatamab (ELRA, BCMA×CD3) combined with carfilzomib and dexamethasone yielded an 83.3% overall response rate with a median duration of response not reached. Mezigdomide (MEZI, CELMoD) showed an 85.7% overall response rate and 17.5-month progression-free survival in Lenalidomide-refractory patients. ISB 2001 (BCMA×CD38×CD3 tri-specific antibody): achieved a 90% overall response rate at ≥ 50 µg/kg in heavily pretreated patients, with low-grade cytokine release syndrome observed. Through multi-targeted design, reversal of drug resistance mechanisms, and optimized combination strategies, treatment approaches for relapsed/refractory multiple myeloma are evolving toward greater precision, durability, and individualization.

Keywords:  CELMoD; Cevostamab; Elranatamab; ISB 2001; Inobrodib; Lisaftoclax; Mezigdomide; Multiple myeloma; Tri-specific antibody

DOI:  https://doi.org/10.1186/s40364-025-00803-0
Blood Neoplasia. 2025 Aug;2(3): 100102

Outcomes at a single institution with MTR induction and consolidation in the management of primary CNS lymphoma.

Nikita K Dave, Veronica Carvajal, Alex C Watts, Jordan S Carter, Michael Cook, Colin Thomas, Donald E Tsai, Stephen J Schuster, James N Gerson, Stefan K Barta, Jakub Svoboda, Elise A Chong, Wei-Ting Hwang, Daniel J Landsburg, Sunita D Nasta.

Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive non-Hodgkin lymphoma. Given its infrequency, there are few randomized trials to guide induction and consolidation strategies, with no consensus on optimal treatment. Most centers will offer high-dose methotrexate-based induction chemotherapy followed by either autologous stem cell transplant, whole-brain radiation, or prolonged chemotherapy. The preferred strategy at our institution has been 6 doses of methotrexate, temozolomide, and rituximab (MTR) induction with methotrexate on day 15 until complete response for induction followed by 6 monthly cycles of MTR. We conducted a retrospective analysis of patients diagnosed with PCNSL at the University of Pennsylvania from 1 April 2008 to 1 October 2024, identifying 153 patients who received this regimen. With a follow-up of 63 months, the median overall survival (OS) in the entire cohort was 65 months, with a median relapse-free survival (RFS) of 36 months. In the cohort of patients who were able to complete 6 months of MTR induction and proceed with MTR consolidation, median OS and RFS were 143 and 122 months, respectively. Although 13% of patients discontinued therapy because of toxicity, there was no treatment-related mortality. These results indicate that prolonged MTR is a safe treatment option and an alternative to intensified consolidation strategies. Further randomized studies are necessary to determine the optimal treatment strategy in newly diagnosed PCNSL.

DOI: https://doi.org/10.1016/j.bneo.2025.100102
Leuk Res Rep. 2025 ;24 100518

Tagraxofusp maintenance post-hematopoietic stem cell transplantation provides long-term survival and manageable safety for a patient with blastic plasmacytoid dendritic cell neoplasm.

Qaiser Bashir, Marina Konopleva, Glorette Abueg, Jeremy Ramdial, Chitra Hosing, Samer A Srour, Amin Alousi, Uday R Popat, Yago Nieto, Gheath Alatrash, Richard E Champlin, Elizabeth J Shpall, Muzaffar Qazilbash, Naveen Pemmaraju.

  Presented here is the case of a 68-year-old woman with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HCT). Prior to allo-HCT, the patient was treated with hydroxyurea and mini-CVD (cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate (Methotrexate) and cytarabine) + venetoclax + TAG for 5 cycles, which induced morphologic complete remission with minimal residual disease. After allo-HCT, the patient had persistent cytogenic abnormalities 45,XX,der(7)add(7)(p13)del(7)(q11.2q22)add(7)(q32),add(12)(p13),-15,del(16)(q23),-17,+22,+2mar[1]/46,XX[19], and was then treated with TAG maintenance therapy at 9 mg/kg on a 28-day cycle for 16 cycles. At mid-treatment (cycle 6 of 16 cycles of TAG) and prior to TAG discontinuation (due to travel burden), the patient was negative for minimal residual disease and was in complete remission. There was no high-grade toxicity or capillary leak syndrome. The patient remains in complete remission as of present day (>17 months CR). This is the first case study illustrating the feasibility of long-term TAG maintenance post-allo-HCT to control BPDCN.

Keywords:  Allogeneic stem cell transplant; BPDCN; Blastic plasmacytoid dendritic cell neoplasm; CD123; Tagraxofusp

DOI:  https://doi.org/10.1016/j.lrr.2025.100518
Leukemia. 2025 Jun 30.

Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial.

Xiaoyuan Gong, Wenbin Liu, Yuntao Liu, Qiuyun Fang, Runxia Gu, Kaiqi Liu, Dong Lin, Chunlin Zhou, Guangji Zhang, Benfa Gong, Shuning Wei, Yan Li, Shouyun Li, Ying Wang, Yimin Hu, Shaowei Qiu, Bingcheng Liu, Ying Wang, Yingchang Mi, Hui Wei, Jianxiang Wang.

Tyrosine kinase inhibitors (TKIs) combined with chemotherapy and immunotherapy evolved as the standard treatment for newly diagnosed (ND) Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Nonetheless, the efficacy and safety of combining TKIs with BCL-2 inhibitors in ND Ph+ ALL have yet to be fully elucidated. Hence, we carried out a prospective clinical trial to explore the efficacy and safety of olverembatinib combined with venetoclax and reduced-intensity chemotherapy as frontline treatment in Ph+ ALL. From October 2022 to March 2024, a total of 79 patients with a median age of 42 years completed a minimum of three cycles of olverembatinib and venetoclax-based regimen. The primary end point of the study was the complete molecular response (CMR) rate at 3 months. Ultimately, the regimen achieved CMR of 62.0% at 3 months in the absence of intensive chemotherapy or immunotherapy. No deaths occurred during the induction phase. With a median follow-up of 12 months, the estimated 1-year overall survival (OS) and event-free survival (EFS) rates were 93.1% (95% CI 86.4-99.8) and 89.1% (95% CI 80.3-97.9), respectively. Transcriptomic data revealed a potential complementary mechanism between TKIs and venetoclax, thereby verifying the rationale for the combination of these two agents. In conclusion, our study provides an alternative treatment strategy for patients with ND Ph+ ALL, particularly for those who are unfit or unavailable for immunotherapy or intensive chemotherapy at the initial stage of treatment. Clinical trial registration: The study was registered at https://clinicaltrials.gov/ with the registration number of NCT05594784.

DOI: https://doi.org/10.1038/s41375-025-02674-8
Cancer. 2025 Jul 01. 131(13): e35963

Chronic myeloid leukemia outcomes according to baseline risk and first-line treatment in real-world settings: Data from the Italian Network/CML Campus.

Valentina Giai, Tiziana Rosso, Fausto Castagnetti, Patrizia Pregno, Massimiliano Bonifacio, Isabella Capodanno, Mario Tiribelli, Fabio Stagno, Giovanni Caocci, Antonella Gozzini, Luigiana Luciano, Sara Galimberti, Monica Bocchia, Andrea Patriarca, Giuseppe Lanzarone, Bruno Martino, Anna Guella, Anna Rita Scortechini, Carmen Fava, Claudio Fozza, Simona Sica, Nicola Di Renzo, Pellegrino Musto, Domenico Pastore, Alessandro Maggi, Michele Pizzuti, Lorella Maria Antonia Melillo, Angelo Michele Carella, Giuseppe Tarantini, Anna Mele, Elisabetta Calistri, Maria Rosaria Coppi, Fabio Saccona, Emilia Scalzulli, Beatrice Battaglio, Miriam Iezza, Cinzia Bitetti, Roberto Freilone, Gianantonio Rosti, Francesco Albano, Fabrizio Pane, Giorgina Specchia, Giovannino Ciccone, Giuseppe Saglio, Massimo Breccia.

   BACKGROUND: Improved outcome has been reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) in sponsored trials.
METHODS: This is a multicenter prospective cohort study of consecutive patients with newly diagnosed chronic phase CML from 19 regions in Italy. Baseline treatments and prognostic factors on time to first optimal molecular response (≥ molecular response 3, MR3), time to disease progression, time to death from CML, and overall survival (OS) were analyzed using multivariable Fine and Gray models.
RESULTS: The authors included 1433 CML patients: 49% (median age, 70 years) treated with frontline imatinib (IMA), and 51% treated with second-generation TKIs (2G-TKIs; median age, 52 years). EUTOS long-term survival (ELTS) was low in 68.1% of 2G-TKIs patients, compared to 50.4% of IMA patients. Faster molecular responses were observed with 2G-TKIs within the first 6 months and maintained thereafter (subhazard ratio [sHR], 1.31; 95% confidence interval [CI], 1.15-1.50). Female gender and low ELTS risk had faster time of response. Achieving major molecular response (MMR or MR3) was associated with reduced risk of progression at 6 and 12 months. Overall, 41 patients progressed without differences between IMA and 2G-TKIs. Intermediate and high risk ELTS showed higher risk of progression and death from CML. Twenty-two CML-related deaths (16.5%) occurred mostly in the first 2 years from diagnosis, higher in 2G-TKIs patients (sHR, 1.75; 95% CI, 0.52-5.87). OS at 5 years was 88% with no clear differences between IMA and 2G-TKIs treatment after adjustment for potential confounders.
CONCLUSIONS: The study confirms faster responses with 2G-TKIs compared to IMA but similar clinical outcomes and a strong prognostic effect of ELTS.

Keywords:  TKI; chronic myeloid leukemia; first‐line treatment; imatinib; real‐life study; risk factors; second generation TKI

DOI:  https://doi.org/10.1002/cncr.35963
Blood Adv. 2025 Jul 02. pii: bloodadvances.2025016665. [Epub ahead of print]

Asciminib for relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

Mathilde Chanut, Aurélie Cabannes-Hamy, Marie Balsat, Nassim Sahki, Emmanuel Raffoux, Yosr Hicheri, Bruno Lioure, Lucie Laemmel, Thibaut Tl Leguay, Victoria Cacheux, Maria Pilar Gallego-Hernanz, Andrea Pieragostini, Gabrielle Roth-Guepin, Ludovic Gabellier, Nathalie Denizon, Lise Willems, Quentin Cabrera, Sylvain P Chantepie, Valérie Coiteux, Claudie Capdupuy, Martin Carre, Antoine Machet, Juliette Lambert, Sandrine Roux, Franck-Emmanuel Emmanuel Nicolini, Nicolas Boissel, Emmanuelle Clappier, Rathana Kim, Philippe Rousselot.

Asciminib (ASC) is an allosteric inhibitor of BCR::ABL1 that binds the myristoylation site of the ABL1 protein. We report the use of ASC in relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and lymphoid blast crisis of chronic myeloid leukemia (LBC-CML) in 41 patients retrospectively collected in France. Median age was 56 years (range: 19-84). Most patients (78%) received ASC as a third-line or later treatment, with 93% previously treated with ponatinib. Twenty-seven out of 35 analyzed patients had BCR::ABL1 mutations, including T315I (n=18) or compound mutations (n=8). ASC was prescribed at 200 mg BID in 83% of the patients, alone (n=20) or in combination (n=21). Overall, 30/36 evaluable patients achieved a composite complete response (CR/CRi), including measurable residual disease negativity (defined by BCR::ABL1/ABL1 <0.01% in bone marrow) in 13/23 patients (57%). The median overall survival and event-free survival (EFS) were 9.8 and 4.9 months respectively. EFS was improved when ASC was administered in combination rather than as monotherapy (7.93 vs 4.23 months). Post-ASC mutations were analyzed in 7 relapsing patients, identifying a new Q252H mutation in 2 cases. In conclusion, our findings suggest that ASC is an effective salvage therapy for Ph+ ALL and LBC-CML.

DOI: https://doi.org/10.1182/bloodadvances.2025016665
Lancet Haematol. 2025 Jun 25. pii: S2352-3026(25)00117-6. [Epub ahead of print]

Optimising T-cell immunotherapy in patients with multiple myeloma: practical considerations from the European Myeloma Network.

EMN Guidelines Committee

Novel T-cell immunotherapies (chimeric antigen receptor [CAR] T cells and T-cell redirecting bispecific antibodies) are changing the treatment landscape of relapsed or refractory multiple myeloma. In this Review, the European Myeloma Network provides recommendations to optimise both safety and efficacy of T-cell immunotherapy. In patients who are eligible for both CAR T-cell therapy and bispecific antibodies, we recommend using CAR T-cell therapy first due to the high response rate and durable progression-free survival, accompanied by improved quality of life. Furthermore, previous bispecific antibody treatment has a negative effect on the efficacy of CAR T-cell therapy, and there is emerging evidence that suggests that relapse after B-cell maturation antigen-directed CAR T-cell therapy can be effectively managed with bispecific antibodies. Timely referral and planning are crucial before initiating T-cell immunotherapy to optimise treatment selection, conduct adequate diagnostic tests (eg, excluding latent infections), and identify modifiable risk factors to improve clinical outcomes. Supportive care is crucial in all patients receiving T-cell immunotherapy to prevent non-relapse mortality.

DOI: https://doi.org/10.1016/S2352-3026(25)00117-6
Discov Oncol. 2025 Jul 01. 16(1): 1202

Combination of venetoclax with CHG regimen in refractory/relapsed T-lymphoblastic lymphoma/acute lymphoblastic leukemia: a case series and literature review.

Mei Zhou, Yuze Yang, Xiaoyan Zhang, Yijie Jiao, Zhenxing Guo.

  T lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is a highly aggressive hematologic malignancy, with particularly poor outcomes for refractory/relapsed (R/R) patients. This article reports the efficacy and safety of V-CHG regimen (Venetoclax, cytarabine, homoharringtonine, G-CSF) in the treatment of three R/R T-LBL/ALL cases. One 69 years old female patient with T-ALL experienced a twice relapse and achieved morphological complete remission (CR) with one cycle of V-CHG regimen. Another 65 years old female patient with T-LBL progressed to T-ALL after continuous CR for 10 months and failed by two different salvage chemotherapy regimens. She achieved minimal residual disease (MRD) negative CR with a third-line treatment based on V-CHG regimen. The third T-ALL patient was a 26 years old male who resistant to VDCP induction regimen and achieved morphological CR with one cycle of V-CHG regimen, and obtained MRD negative CR after second cycle treatment. All the three patients were well tolerated to the V-CHG regimen. The results of this study indicate that the V-CHG regimen is effective and safe for R/R T-LBL/ALL, warranting further application in the future.

Keywords:  CHG regimen; Homoharringtonine; Refractory/relapsed; T lymphoblastic lymphoma/T acute lymphoblastic leukemia; Venetoclax

DOI:  https://doi.org/10.1007/s12672-025-03055-4
Blood Adv. 2025 Jul 01. pii: bloodadvances.2025016911. [Epub ahead of print]

Tocilizumab Prophylaxis for Patients with Multiple Myeloma Treated with Bispecific Antibodies.

Andrew Kowalski, Jillian Lykon, Benjamin T Diamond, David G Coffey, Marcella Kaddoura, Francesco Maura, James E Hoffman, Abhishek Pandey, Dickran Kazandjian, Carl Ola Landgren.

Bispecific antibodies for treatment for multiple myeloma are highly effective but commonly cause cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Emerging data indicate that prophylactic tocilizumab may reduce CRS, without impacting efficacy. We administered a single dose of tocilizumab prior to the first dose of bispecific antibodies to 119 patients to determine the impact on CRS in a real-world setting including BCMAxCD3- and GPRC5DxCD3-targeted antibodies. The best overall response rate (ORR) was 65.7% (binomial 95%CI: 55.8%-74.7%). We observed a low overall rate of CRS (10.1%: 5.3%-17%). For teclistamab, elranatamab, linvoseltamab and talquetamab individually, the CRS rate was 8.9%, 12.5%, 0%, and 13%. The overall ICANS (5.9%: 2.4%-11.7%) was low, but similar to rates without prophylactic tocilizumab. CRS was limited to grade 1 for 10 of 12 events. There were no grade 3 CRS events, and no additional doses of tocilizumab or corticosteroids were given for CRS. Our real-world evidence results suggest that tocilizumab may be effective as a preventative, rather than reactive, measure to prevent CRS without compromising efficacy.

DOI: https://doi.org/10.1182/bloodadvances.2025016911
Blood. 2025 Jul 03. 146(1): 7-8

Another 1q bites the dust.

Vikas A Gupta, Lawrence H Boise.

DOI: https://doi.org/10.1182/blood.2025028903
Leuk Res Rep. 2025 ;24 100517

Management of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia in a Jehovah's Witness using chemotherapy free regimen: A case report and review of literature.

Muhammad Hassan Raza, Eiraj Khan, Alexis M Desjarlais, Salman Fazal.

   Introduction and Importance: Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (pH-positive ALL) in Jehovah's Witness (JW) using chemotherapy agents, opens an ethically and morally challenging paradigm instead of their religious practices.
Case Presentation: We present a case of pH-positive B cell ALL in a Jehovah's Witness patient who refused the transfusion of blood as a part of their treatment regimen. We intended to treat this patient using a new "chemotherapy-free" approach and achieved Minimal Residual Disease (MRD) negative state with durable outcomes for the next three years.
Clinical Discussion: With "chemotherapy-free" regimen, we achieved complete molecular remission without any significant side effects in our patient.
Conclusion: Chemo-free approach is a promising opportunity to treat Jehovah's witnesses with pH-positive B cell ALL as the haemoglobin and platelets remained above transfusion thresholds. However, further research is required to fully understand and implement this approach. Future clinical trials should consider including this unique patient population to better understand their needs and improve outcomes.

Keywords:  ALL; Allo-SCT; CMR; CSAs; ESAs; HSCT; JW; MRD; TKI; TSAs

DOI:  https://doi.org/10.1016/j.lrr.2025.100517
NPJ Precis Oncol. 2025 Jul 01. 9(1): 211

Functional cure with single agent olutasidenib in relapsed IDH1/NPM1 co-mutated AML.

Justin Watts, Tiffany Nong, Katarina Micin, Deborah Soong, Ellen Madarang, Maurizio Affer, Shefali Mehra, Jessica Alvarez Lesmes, Jennifer Chapman, Yi Zhou, Amber Thomassen, Terrence Bradley, Tulasigeri Totiger, Ronan Swords, Justin Taylor.

Olutasidenib is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that was recently approved by the US FDA for adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring mutant IDH1. In the pivotal Phase II trial of olutasidenib, the median duration of complete response (CR) was 28.1 months. Here we report the first patient in the world to receive olutasidenib, for relapsed NPM1 and IDH1 co-mutated AML, who remains in continuous CR for over 7 years on olutasidenib monotherapy. We detail the clinical course as well as the pathologic and genomic evolution of the disease. Furthermore, using a novel single cell measurable residual disease assay and digital PCR and qPCR for the detection of IDH1 and NPM1 mutations, we found no evidence of residual detectable leukemia. To our knowledge, this is the first report of an AML patient functionally cured by IDH1 inhibitor monotherapy.

DOI: https://doi.org/10.1038/s41698-025-01013-5
Blood. 2025 Jul 03. 146(1): 9-11

SRSF2-mutated MDS: bortezomib STAT?

Aly Karsan.

DOI: https://doi.org/10.1182/blood.2025029269
Expert Rev Hematol. 2025 Jun 27.

Non- MPL-W515K/L mutations in myeloproliferative neoplasms: insights from two case reports and a review of the literature.

Ane Sofie Tønne Nesse, Hilde Kollsete Gjelberg, Miriam Sandnes, Rakel Brendsdal Forthun, Håkon Reikvam.

BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) result from clonal proliferation of hematopoietic stem cells, and include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Key driver mutations in the JAK2, CALR, and MPL genes are important for diagnosis and differentiation of triple-negative cases. The MPL gene, particularly exon 10, harbors mutation hotspots influencing pathogenesis and prognosis.
RESEARCH DESIGNAND METHODS: Thisstudy presents two cases of atypical MPLmutations in MPN-patients and investigates the prevalence ofnon-canonical MPLmutationsin the literature.
RESULTS: Wereport two MPN cases with non-canonical MPLmutations (S204P and W515R) detected by next-generation sequencing.We also conducted a systematic review of the PubMed database,identifying 68 cases of non-W515L/K MPLmutations. A total of 86 mutations were identified, comprised of 32unique non-canonical mutations. W515R/S/A were the most frequent(31%), followed by V501A/M (15%) and S505N/C (13%). 59% of patientshad ET, 24% PMF and 13% post-ET/PV MF. Most mutations (71%) occurredin exon 10. 26% harbored concurrent JAK2,CALR andMPLmutations.
CONCLUSIONS: Ourfindings highlight the importance of non-canonical mutations indiagnosis of MPN to prevent misclassification and improve patientmanagement. Understanding these mutations could lead to more tailoredtreatments and better outcomes in MPN patients.

DOI: https://doi.org/10.1080/17474086.2025.2527345
Blood Adv. 2025 Jul 02. pii: bloodadvances.2024015322. [Epub ahead of print]

BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma.

Claudia Pignataro, Pietro Zoppoli, Luca Vincenzo Cappelli, Liron Yoffe, Marta Moretti, Mariapaola Izzo, Selene Mallia, Clarisse Kayembe, Abigail Taylor, Gianluca Petrillo, Alessandra Affinito, Cristina Quintavalle, Giada De Luca, Martina Mascolo, Sara Verde, Aurelia Fraticelli, Alessia Ciarrocchi, Paolo Salerno, Enrico De Smaele, Antonio Francesco Campese, Valentina Fragliasso, Robin Foà, Giuseppe Merla, Giorgio Ga Inghirami, Gerolama Condorelli, Danilo Fiore.

Resistance to first-line chemotherapies and crizotinib in anaplastic large cell lymphoma (ALCL) represents a significant challenge, often leading to a dismal outcome. Despite recent advancements, the dissection of the intrinsic and extrinsic molecular alterations underlying crizotinib resistance in ALCL is still poorly understood. Here, we transcriptionally unraveled the bidirectional interplay between anaplastic lymphoma kinase (ALK)-driven ALCL (ALK+ ALCL) and stromal cells in the presence of crizotinib at bulk and single-cell levels, and identified that the microenvironment provides pro-survival signals leading to crizotinib persistence in ALK+ ALCL. We detected increased BCL2 expression, and downregulation of pathways related to apoptosis in crizotinib-persister ALK+ ALCL cells. Further, we predicted in silico the ligand-receptor interactions between tumoral and stromal cells, supporting their contribution to ALCL pathogenesis mainly participating in the adhesion/membrane transport, triggering receptors, and promoting activation and microenvironment stimulation in lymphoma cells. Finally, we explored the effect of crizotinib in combination with BH3 mimetics. Pharmacologic and genetic ablation of anti-apoptotic targets displayed a significant synergistic effect with crizotinib, overcoming the stroma-mediated protection of lymphoma cells upon drug treatment. Thus, BCL2/BCL-XL targeting is synthetic lethal with crizotinib exposure in ALK+ ALCL and represents an intrinsic and extrinsic-mediated targetable vulnerability in lymphoma cells challenged with crizotinib. Our data supports the evaluation of BCL2 targeting in crizotinib-based regimens in the management of ALK+ ALCL patients.

DOI: https://doi.org/10.1182/bloodadvances.2024015322
Haematologica. 2025 Jul 03.

BTKi +humanized anti-CD20 for advanced follicular lymphoma: ready for an ALTERNATIVE?

Irene Dogliotti, Massimo Federico.

Not available.

DOI: https://doi.org/10.3324/haematol.2025.288196
Adv Exp Med Biol. 2025 ;1480 371-386

Oral and Intravenous Iron Therapy.

Andrea U Steinbicker, Kostas Pantopoulos.

  Pre-anemic iron deficiency and iron deficiency anemia are the most common health conditions. They are mostly caused by blood loss and/or inadequate dietary iron absorption and are managed with iron replacement therapy. The goal of iron replacement therapy is to correct anemia and replenish iron stores. In most patients, oral iron is typically the first choice for treatment due to its ease of use, over-the-counter availability, and low cost of most common formulations. Ferrous sulfate remains the gold standard for oral iron therapy, but alternative formulations have also been developed. Effective iron repletion requires the daily intake of up to 200 mg elemental iron for 3-12 weeks. However, only a small fraction of it gets absorbed. Thus, accumulation of unabsorbed iron in the intestinal lumen may cause constipation and other gastrointestinal side effects. Intravenous iron is the preferred treatment for patients who are intolerant or refractory to oral iron or require rapid correction of anemia and repletion of iron stores, for example prior to surgery. The newest formulations such as ferric carboxymaltose and ferric derisomaltose have excellent safety profiles and can be provided at high doses of 500-1000 mg in a single infusion. Intravenous iron should always be administered in medical facilities by healthcare providers trained to manage potential but rare hypersensitivity reactions. Moreover, phosphate levels should be monitored in patients because intravenous iron formulations, especially ferric carboxymaltose, have been associated with increased risk for hypophosphatemia.

Keywords:  Hypophosphatemia; Intravenous (IV) iron therapy; Iron deficiency anemia (IDA); Iron replacement therapy; Oral iron supplements

DOI:  https://doi.org/10.1007/978-3-031-92033-2_24