bims-hemali 2025-04-06 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–04–06
eighteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Efficacy of venetoclax combined with homoharringtonine and cytarabine for younger adults with newly diagnosed AML.
Outcomes of patients with multiple myeloma undergoing autologous transplant with suboptimal pretransplant response.
Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study.
Molecular response of a patient with e19a2-positive chronic myeloid leukemia to flumatinib: a case report and literature review.
Oral decitabine cedazuridine with and without venetoclax in higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia: a propensity score-matched study.
Real-World Data on Outcome of Burkitt Lymphoma and Burkitt Leukemia Treated According to the GMALL B-ALL/NHL 2002 Protocol: A Tertiary Center Experience.
Glofitamab induces deep and rapid response in relapsed primary central nervous system lymphoma.
Efficacy and safety of zanubrutinib combined with chimeric antigen receptor T-cell therapy targeting CD19 in refractory or relapsed diffuse large B cell lymphoma: A retrospective analysis.
The immunotherapy real estate of Hodgkin lymphoma.
Early identification of functional high-risk multiple myeloma patients after transplant: the predictive power of fat fraction and Response Assessment Category score in diffusion-weighted whole-body magnetic resonance imaging.
Characteristics and Outcomes of Patients with Double Refractory and Double Exposed Chronic Lymphocytic Leukemia.
Real-world data of siltuximab for Chinese patients with iMCD: combination with BCD regimen as a potential approach for severe cases.
Primary mediastinal B-cell lymphoma (PMBCL): The LYSA pragmatic guidelines.
Venetoclax schedule in AML: 7 vs 14 vs 21 vs 28 days.
Carfilzomib prescribing patterns and outcomes for relapsed or refractory multiple myeloma: a real-world analysis.
A phase IIb study of selinexor in combination with daratumumab in patients with daratumumab-refractory multiple myeloma.
Efficacy of a Novel BCL-xL Degrader, DT2216, in Preclinical Models of JAK2-mutated Post-MPN AML.
VEN in combination with 10-day DEC in newly diagnosed elderly or relapsed/refractory acute myeloid leukemia, and high-risk myelodysplastic syndrome: long term follow-up of a phase 2 trial.

Ann Hematol. 2025 Apr 04.

Efficacy of venetoclax combined with homoharringtonine and cytarabine for younger adults with newly diagnosed AML.

Bao-Quan Song, Xin Kong, Yin Liu, Yan Pu, Jian Zhang, De-Pei Wu, Hui-Ying Qiu.

  Venetoclax (VEN)--based induction therapy has demonstrated considerable promise in treating acute myeloid leukemia (AML); however, the optimal VEN-based combination therapy remains to be established. This study evaluated the efficacy and safety of the venetoclax-homoharringtonine-cytarabine (VHA) regimen in patients with newly diagnosed (ND) AML. A retrospective analysis was conducted on 55 patients treated with the VHA regimen. The overall response rate (ORR) was 92.7% (51/55, 95% CI 82%-98%), and the composite complete remission (CRc) rate was 87.3% (48/55, 95% CI 76%-95%). Among the 48 patients who achieved CRc, 91.7% (44/48, 95% CI 67%-90%) achieved complete remission (CR), and 85.4% (41/48, 95% CI 72%-94%) reached measurable residual disease (MRD)-negative CR. In the adverse-risk group, ORR and CRc were 95% (19/20, 95% CI 75%-100%) and 75% (15/20, 95% CI 51%-91%), respectively. The most common grade 3-4 adverse events were febrile neutropenia (32.7%), pneumonia (16.3%), and sepsis (9.1%). Median overall survival (OS) was 26 months, while event-free survival (EFS) was not reached. One-year OS was 83%, and one-year EFS was 82%. These preliminary data suggest that the VHA regimen achieves a very high rate of CR and low toxicity, particularly for adverse-risk AML patients.

Keywords:  Acute myeloid leukemia; Cytarabine; Homoharringtonine; Venetoclax

DOI:  https://doi.org/10.1007/s00277-025-06250-z
Br J Haematol. 2025 Mar 30.

Outcomes of patients with multiple myeloma undergoing autologous transplant with suboptimal pretransplant response.

Oren Pasvolsky, Muhammad Bilal Abid, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Asiya Jatoi, Hina N Khan, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Umer Siddiqui, Yosra Aljawai, Partow Kebriaei, Hans C Lee, Krina K Patel, Mahmoud R Gaballa, Sheeba K Thomas, Robert Z Orlowski, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash.

  There are scarce data in the literature focusing on newly diagnosed multiple myeloma (NDMM) patients who undergo autologous haematopoietic cell transplantation (autoHCT) after achieving suboptimal response to induction. To address this, we performed a retrospective, single-centre analysis of patients with NDMM who underwent upfront autoHCT between 2005 and 2021 with a pretransplant response of less than very good partial response (<VGPR). Primary outcomes were progression-free survival (PFS) and overall survival (OS). 1109 patients were included in our analysis. Median PFS and OS for the entire cohort were 38.6 (95% confidence interval [CI], 35.9-41.9) months and 103.8 (95% CI, 96.4-113.2) months, respectively. Patients with high-risk cytogenetic abnormalities (HRCA) had a median PFS and OS of 24.8 months and 69.9 months respectively. In multivariable analysis, the use of post-transplant maintenance (hazard ratio [HR] 0.75, p = 0.001 and HR 0.75, p = 0.008) and achieving complete response (CR) at best post-transplant response (HR 0.60, p < 0.001 and HR 0.51, p < 0.001) were associated with superior PFS and OS respectively. In conclusion, NDMM patients who received upfront autoHCT with a pretransplant response of <VGPR had a median PFS of >3 years and median OS of >8 years. Post-transplant maintenance further improved survival outcomes.

Keywords:  VGPR; autologous haematopoietic cell transplantation; multiple myeloma; outcomes

DOI:  https://doi.org/10.1111/bjh.20062
Blood Cancer J. 2025 Apr 03. 15(1): 53

Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study.

Carlyn Rose Tan, Sireesha Asoori, Chiung-Yu Huang, Larissa Brunaldi, Rakesh Popat, Efstathios Kastritis, Joaquin Martinez-Lopez, Radhika Bansal, Andre De Menezes Silva Corraes, Saurabh Chhabra, Ricardo Parrondo, Sikander Ailawadhi, Despina Fotiou, Meletios A Dimopoulos, Kwee Yong, Catriona Mactier, Chris Lau, Magdalena Corona, Adolfo Jesús Sáez Marin, Hira Mian, Brian Gm Durie, Saad Z Usmani, Thomas G Martin, Yi Lin.

Teclistamab, a BCMAxCD3-directed bispecific antibody, has shown high response rates and durable remissions in triple-class-exposed patients with relapsed/refractory multiple myeloma. We performed a retrospective study evaluating the efficacy and safety of teclistamab in 210 patients treated at 9 academic centers from five countries within the IMWG Immunotherapy Working Group Committee. Patients were heavily pretreated, with 83% having triple-class refractory disease and 44% with prior BCMA-targeted therapy. With a median follow-up of 5.3 months, the overall response rate (ORR) was 67% in 188 response-evaluable patients, including 55% with a very good partial response or better. The 6-month progression-free survival (PFS) and overall survival rates were 53% (95% CI, 46-61%) and 73% (67-80%), respectively. Patients who received prior BCMA-directed therapy compared to BCMA-treatment-naïve patients had a lower ORR (58.3 vs 74.0%; P = 0.03) and PFS (6-month PFS 43% [95% CI, 33-55%] vs 63% [54-73%]; logrank P = 0.004). Step-up dosing occurred in an outpatient setting for 23% of patients. CRS occurred in 54% of patients, and infections were reported in 56.2% of patients, with 22% having grade ≥3 infections. In this multicenter real-world study, we found that teclistamab can lead to rapid responses in heavily pretreated myeloma patients with comparable efficacy and safety profiles, as demonstrated in MajesTEC-1.

DOI: https://doi.org/10.1038/s41408-025-01259-z
Front Med (Lausanne). 2025 ;12 1515002

Molecular response of a patient with e19a2-positive chronic myeloid leukemia to flumatinib: a case report and literature review.

Yaqing Feng, Hongjin Wang, Lidong Zhang, Jinying Gong, Xi Liu, Caiqin Mu, Jun Qiao, Haitao Meng, Yanfang Zhang.

   Objective: Chronic myeloid leukemia (CML) is a malignancy driven by the BCR::ABL1fusion gene, with the e19a2 transcript being a rare variant, accounting for 0.4% of CML cases. Patients with the e19a2 transcript often show poor response to first-line treatment with imatinib, and no standard therapy has been established for this subtype.
Methods: We report a case of a 28-year-old female with e19a2-positive CML. The patient exhibited poor response and tolerance to dasatinib. After 6 months, she achieved partial cytogenetic response (PCyR) but developed grade 3 pleural effusion. Following treatment discontinuation and prednisone therapy, the patient continued dasatinib (80 mg/d). At 12 months, the patient achieved complete cytogenetic response (CCyR), but BCR::ABL1 levels remained suboptimal, with recurrent pleural effusion. The patient was then switched to flumatinib (600 mg/d), achieving major molecular response (MMR) at 6 months and deep complete molecular response (MR4.5) at 24 months, with good tolerance.
Conclusion: Flumatinib demonstrated excellent deep molecular response and good tolerability in e19a2-positive CML patients, suggesting that it may be one of the preferred treatment options for such patients.

Keywords:  chronic myeloid leukemia; e19a2 transcript; flumatinib; molecular response; second-generation tyrosine kinase inhibitor

DOI:  https://doi.org/10.3389/fmed.2025.1515002
Blood Cancer J. 2025 Mar 31. 15(1): 50

Oral decitabine cedazuridine with and without venetoclax in higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia: a propensity score-matched study.

Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D DiNardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James McCloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero.

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched using a propensity score approach that was based on the IPSS-M score and age. All patients had excess blasts; 84% were diagnosed with MDS and 16% with CMML. Most patients had high- or very high-risk disease, according to the revised IPSS-R. The overall response rate was superior in the DEC-C-Ven cohort (90% vs 64%, P = 0.002). The median times to best response were 1.1 and 2.7 months for the DEC-C-Ven and DEC-C cohorts, respectively (P < 0.001). More patients underwent hematopoietic stem cell transplantation in the DEC-C-Ven cohort (47%) than in the DEC-C cohort (16%, P < 0.001). The 4- and 8-week mortality did not significantly differ between the DEC-C and DEC-C-Ven cohorts. Patients in the DEC-C-Ven cohort had a more profound neutropenia at days 15 and 21 of the first cycle. The median overall survival was 24 and 19 months for the DEC-C-Ven and DEC-C cohorts, respectively (P = 0.89), and the median event-free survival durations were 18 and 10 months (P = 0.026). In conclusion, the addition of Ven resulted in improved response rates and outcomes in specific subgroups; prospective clinical trials are needed to confirm these findings.

DOI: https://doi.org/10.1038/s41408-025-01245-5
Clin Lymphoma Myeloma Leuk. 2025 Mar 05. pii: S2152-2650(25)00078-3. [Epub ahead of print]

Real-World Data on Outcome of Burkitt Lymphoma and Burkitt Leukemia Treated According to the GMALL B-ALL/NHL 2002 Protocol: A Tertiary Center Experience.

Ricardo Kosch, Christoph Schaefers, Christian Frenzel, Walter Fiedler, Katja Weisel, Carsten Bokemeyer, Christoph Seidel, Finn-Ole Paulsen.

   INTRODUCTION: Burkitt lymphoma (BL) or leukemia represents a highly aggressive B-cell malignancy requiring intense therapy. Although various different protocols have emerged, few real-world data exist for the GMALL B-ALL/NHL 2002 regimen. Comparative analyses remain challenging because of the disease's rarity.
METHODS: This retrospective study examined the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity in adult patients (pts) with histologically confirmed BL who received the GMALL protocol at the University Medical Center Hamburg-Eppendorf (2012-2022). Statistical analysis identified prognostic factors affecting outcomes.
RESULTS: A total of 48 pts (median age 51.5 years, range 22-78) were included. Most presented with Ann Arbor stage IV (68.7%) and high-risk disease by the BL-IPI (54.1%). Burkitt leukemia was present in 27.1%, HIV positivity in 27%, and CNS involvement in 18%. The ORR was 81.6% (73.5% complete response, 8.1% partial response). After a median follow-up of 38 months (range 0-103), the median PFS and OS were not reached; 3-year rates for both PFS and OS were 73%. While not confirmed in multivariate analysis, Burkitt leukemia (HR 3.86, P = .021) and any bone marrow involvement (HR 3.80, P = .049) emerged as adverse prognostic indicators. Severe mucositis (grade ≥ 3) was common (91.7%), and 87.5% experienced at least one febrile neutropenia episode. No grade 5 treatment-related toxicity was observed.
CONCLUSION: These real-world findings underscore the efficacy of the GMALL protocol in BL management, with outcomes comparable to established regimens but coupled with high toxicity rates. Further comparative trials are essential to define the optimal therapeutic strategy.

Keywords:  Central nervous system; Febrile neutropenia; Infiltration mucositis; Intensive chemotherapy; Non-Hodgkin lymphoma

DOI:  https://doi.org/10.1016/j.clml.2025.03.001
Leuk Lymphoma. 2025 Apr 02. 1-6

Glofitamab induces deep and rapid response in relapsed primary central nervous system lymphoma.

Weiya Wang, Meiyu Chen, Jin Li, Jie Liu, Ting Wang, Qian Song, Xuzhang Lu, Tao Chen, Zhuxia Jia.

  Relapsed refractory primary central nervous system lymphoma (R/R PCNSL) has no recognized optimal therapy due to its grave prognosis and high mortality. This report describes a 69-year-old patient with primary central nervous system lymphoma (PCNSL) who rapidly relapsed after achieving complete remission (CR) on first-line treatment and subsequently received treatment with glofitamab to achieve CR again. Grade 1 cytokine release syndrome was observed and there were no fatal side effects. However, limited reports on glofitamab therapy are applied for relapsed and refractory PCNSL. Further ex vivo data demonstrated that glofitamab drove T cell activation and killing ability against lymphoma cells. Our study suggested that glofitamab may be a viable option for relapsed PCNSL patients.

Keywords:  CD20 × CD3; DLBCL; Glofitamab; PCSNL

DOI:  https://doi.org/10.1080/10428194.2025.2484365
Cancer Treat Res Commun. 2025 Mar 29. pii: S2468-2942(25)00040-1. [Epub ahead of print]43 100902

Efficacy and safety of zanubrutinib combined with chimeric antigen receptor T-cell therapy targeting CD19 in refractory or relapsed diffuse large B cell lymphoma: A retrospective analysis.

Jinhuan Xu, Xiaoying Zhang, Yun Li, Fankai Meng, Yicheng Zhang, Miao Zheng.

   BACKGROUND: While chimeric antigen receptor T-cell (CAR T) therapy has shown promise in treating B-cell non-Hodgkin lymphoma, its efficacy is variable in patients with poor initial responses. This study investigates the efficacy and safety of zanubrutinib combined with CAR T therapy targeting CD19 in refractory/relapsed diffuse large B cell lymphoma (DLBCL).
METHODS: We conducted a retrospective study of 17 patients with R/R DLBCL who received zanubrutinib combined with anti-CD19 CAR T-cell therapy. We assessed overall survival (OS) and progression-free survival (PFS) and conducted subgroup analyses. We also monitored CAR T-cell expansion by quantifying vector copy numbers (VCN). Safety and tolerability were assessed by documenting adverse events, including cytokine release syndrome and neurotoxicity.
RESULTS: The median follow-up was 30 months (range, 4-36). The overall response rate(ORR) was 88.2 %, with 70.5 % achieving complete remission. At 24 months, the estimated PFS was 59 % (95 %CI, 40-88 %), and the OS was 71 % (95 %CI, 52-90 %). At 36 months, the estimated OS was 65 % (95 %CI, 46-92 %). Patients with non-elevated lactate dehydrogenase(LDH) levels showed a higher PFS probability (100 %) compared to those with elevated LDH (42 %, 95 %CI: 21 %-81 %) (log-rank, p = 0.071). The area under the receiver-operating characteristic (ROC) curve for peak CAR T-cell expansion was 0.773, suggesting an optimal cutoff at day 13 for enhancing survival (sensitivity 66.7 %, specificity 90.9 %; p = 0.07). Early peak expansion (before day 13) correlated with better PFS and OS (log-rank, p = 0.0018 and p = 0.0053, respectively). The total VCN AUC was 0.636, with a cutoff of 12,690 significantly predicting survival (sensitivity 83.3 %, specificity 72.7 %; p = 0.366). Kaplan-Meier analysis indicated statistically significant differences in OS for patients with VCN below 12,690 (log-rank, p = 0.017) in comparison to those exceeding 12,690, though trends in PFS did not reach statistical significance (log-rank, p = 0.12). Safety profiles indicated manageable cytokine release syndrome, with no severe neurotoxicity reported.
CONCLUSIONS: Zanubrutinib combined with CAR T-cell therapy offers an effective treatment option for patients with R/R DLBCL, enhancing response rates and survival. Detailed analysis of CAR T-cell expansion provides insight into the dynamics of cellular responses, underscoring the potential for tailored therapeutic approaches based on biological markers.

Keywords:  CAR T-cell; Chimeric antigen receptors; Efficacy and safety; Refractory/relapsed diffuse large B cell lymphoma; Zanubrutinib

DOI:  https://doi.org/10.1016/j.ctarc.2025.100902
Blood. 2025 Apr 03. 145(14): 1445-1447

The immunotherapy real estate of Hodgkin lymphoma.

Christian Steidl.

DOI: https://doi.org/10.1182/blood.2024027782
Haematologica. 2025 Apr 03.

Early identification of functional high-risk multiple myeloma patients after transplant: the predictive power of fat fraction and Response Assessment Category score in diffusion-weighted whole-body magnetic resonance imaging.

Angelo Belotti, Barbara Frittoli, Sofia Terlizzi, Rossella Ribolla, Claudia Crippa, Chiara Saeli, Samantha Ferrari, Nicola Bianchetti, Chiara Bottelli, Chiara Cattaneo, Carmela Carbone, Alessandro Gullino, Marco Chiarini, Viviana Giustini, Aldo Roccaro, Luigi Grazioli, Alessandra Tucci.

Functional high-risk (FHR) multiple myeloma (MM) patients, defined as those with early relapse despite optimal initial therapy, represent an unmet clinical need. Diffusionweighted whole-body MRI (DW-MRI) is increasingly used in MM management due to its high sensitivity in assessing treatment response. The Myeloma Response Assessment and Diagnosis System (MY-RADS) established the Response Assessment Category (RAC), a 5-point scale ranging from complete response (RAC 1) to progressive disease (RAC 5), which independently stratifies patients with different outcomes after autologous stem cell transplantation (ASCT). The relative Fat Fraction (rFF), derived from DW-MRI, provides additional prognostic insights into bone marrow composition. This study aimed to evaluate whether the combined assessment of RAC and rFF could identify FHR MM patients at risk of early relapse, defined as progression within 18 months post-ASCT. Ninety-seven MM patients were retrospectively analyzed after ASCT, before maintenance, with a median follow-up of 47 months. An rFF threshold of 17.2% predicted early relapse with 83% sensitivity and 85% specificity. Patients with rFF >17.2% had significantly improved post-ASCT progression-free survival (PFS, median not reached vs. 13.7 months, HR 0.18; 95% CI 0.08-0.43) and overall survival (OS, 3-year rate: 96% vs. 62%, HR 0.12; 95% CI 0.03-0.45) compared to rFF ≤17.2%. Patients with RAC 1/rFF High had the best outcomes, while RAC ≥2/rFF Low had the worst prognosis (median PFS: NR vs. 12.3 months, HR 0.21; 95% CI 0.07-0.62). rFF complements RAC for response assessment after ASCT, enabling early identification of FHR patients with poor prognosis.

DOI: https://doi.org/10.3324/haematol.2025.287409
Blood Adv. 2025 Apr 03. pii: bloodadvances.2025016006. [Epub ahead of print]

Characteristics and Outcomes of Patients with Double Refractory and Double Exposed Chronic Lymphocytic Leukemia.

James T Yoon, Yinglu Zhou, Mariia Mikhaleva, Daniel Sungchul Choi, Stacey M Fernandes, Philippe Armand, Amy C Bessnow, Jennifer L Crombie, David C Fisher, Eric D Jacobsen, Caron A Jacobson, Austin I Kim, Ann S LaCasce, Reid W Merryman, Oreofe O Odejide, Erin M Parry, David A Qualls, Christine E Ryan, Aswin Sekar, Jacob D Soumerai, Jon E Arnason, Svitlana Tyekucheva, Matthew S Davids, Jennifer R Brown, Inhye E Ahn.

We analyzed the characteristics and outcomes of 95 patients with chronic lymphocytic leukemia (CLL) post-Bruton tyrosine kinase inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i) failure. To clearly distinguish sensitivity and resistance to the targeted treatment classes, we defined double refractory (DR) CLL when progressive disease occurred during active treatment with a BTKi and a BCL2i given sequentially or in combination and double exposed (DE) disease when treatment with either or both of these agents was discontinued due to reasons other than progression. Thirty (31.6%) patients had DR CLL and 65 (63.2%) had DE CLL. The DR group more frequently had unmutated IGHV (97%), TP53 aberration (73%), and BTK mutations (59%) than the DE group (75%, 46%, and 27%, respectively). The median number of total lines of therapy was 6 for DR and 3 for DE. Nearly all (97%) DR patients required subsequent therapy after developing DR CLL. The most commonly used treatment was non-covalent BTKis (34%), followed by concurrent covalent BTKi and BCL2i (28%) and CD19 chimeric antigen receptor-modified T cells (24%). Treatment for DE CLL was less frequently observed (26%). Median overall survival (OS) was 2.2 years once DR developed despite frequent initial responses to non-covalent BTKis or cellular therapy in the cohort. Patients with DE CLL demonstrated favorable survival (median OS not reached) and durable response to subsequent therapy.

DOI: https://doi.org/10.1182/bloodadvances.2025016006
Ann Hematol. 2025 Apr 03.

Real-world data of siltuximab for Chinese patients with iMCD: combination with BCD regimen as a potential approach for severe cases.

Si-Yuan Li, Yu-Han Gao, Yue Dang, Long Chang, Kai-Ni Shen, Hua-Cong Cai, Dan-Qing Zhao, Chong Wei, Jun Feng, Lu Zhang, Jian Li.

  Idiopathic multicentric Castleman disease (iMCD) is a rare disease characterized by polyclonal lymphoproliferation and systemic inflammation. Siltuximab, targeting interleukin-6 (IL-6), has been recommended as the first-line therapy for iMCD. However, substantial real-world data from China were still lacking, and treatment for patients with severe iMCD remained challenging. This single-center retrospective study investigated the real-world efficacy and safety of siltuximab-based therapy in 43 consecutive patients with iMCD in China from July 2022 to March 2024. The overall response rate (including symptomatic and biochemical response) was 59% at week 3 and increased to 91% at week 12, with complete and partial response rates of 54% and 37%, respectively. Patients who received siltuximab as a first-line treatment exhibited better treatment response (OR = 0·040, 95% CI, 0·004 - 0·390, p = 0·006). Inflammatory markers (such as interleukin-6 and high-sensitivity C-reactive protein [hsCRP]) and pathologic types showed no predictive role in the treatment responses. Eighteen patients, who were all classified as severe iMCD, received combined therapy of siltuximab and BCD regimen (bortezomib, cyclophosphamide and dexamethasone). Of them, the overall response rate was 50% at week 3, which increased to 100% at week 12. Our findings reinforced the existing evidence on the efficacy and safety of siltuximab and highlighted the potential benefits of combining siltuximab with BCD regimen in severe iMCD patients.

Keywords:  Combination therapy; Idiopathic multicentric castleman disease; Response rate; Siltuximab

DOI:  https://doi.org/10.1007/s00277-025-06329-7
Eur J Cancer. 2025 Mar 22. pii: S0959-8049(25)00150-9. [Epub ahead of print]220 115369

Primary mediastinal B-cell lymphoma (PMBCL): The LYSA pragmatic guidelines.

Loïc Renaud, Marie Donzel, Justine Decroocq, Pierre Decazes, Jean Galtier, Barbara Burroni, Elena-Liana Veresezan, Côme Sesboüé, Peggy Dartigues, Catherine Chassagne-Clément, Laurent Martin, Claire Mauduit, Sophie Kaltenbach, Dominique Penther, Pascaline Etancelin, David Sibon, Sarah Bailly, Valentine Martin, Eric Durot, Youlia Kirova, Adrien Grenier, Marie Maerevoet, Wivine Bernard, Louise Naveau, Aurélie Cabannes-Hamy, Anne-Ségolène Cottereau, Nicolas Jacquet-Francillon, Robin Noel, Thibaut Reichert, Clémentine Sarkozy, Lucile Bussot, Sébastien Bailly, Sandy Amorim, Daphné Krzisch, Jérôme Cornillon, Hugo Legendre, Florian Chevillon, Doriane Cavalieri, Pierre Sesques, Véronique Minard-Colin, Corinne Haioun, Franck Morschhauser, Roch Houot, Fabrice Jardin, Hervé Tilly, Alexandra Traverse-Glehen, Vincent Camus.

  Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of large B-cell lymphoma with unique clinical, histopathological, and molecular characteristics. Despite its aggressive nature, PMBCL has a high cure rate when managed appropriately. Advances in the understanding of PMBCL biological characteristics, coupled with improvements in diagnostic tools and therapeutic approaches, have significantly improved patient outcomes in recent years. In this article, we present a set of pragmatic guidelines developed by the Lymphoma Study Association (LYSA) for the management of PMBCL. These guidelines address key aspects of diagnosis, staging, response evaluation, and treatment, integrating the latest evidence from clinical trials, expert consensus, and real-world practice. The aim of the guidelines is to provide clinicians with a clear, practical framework to optimize care for patients with PMBCL, ensuring that the best available evidence is translated into clinical practice.

Keywords:  Guidelines; LYSA; Primary mediastinal B-cell lymphoma

DOI:  https://doi.org/10.1016/j.ejca.2025.115369
Blood Cancer J. 2025 Apr 03. 15(1): 56

Venetoclax schedule in AML: 7 vs 14 vs 21 vs 28 days.

Naseema Gangat, Ayalew Tefferi.

Venotoclax schedule in acute myeloid leukemia.

DOI: https://doi.org/10.1038/s41408-025-01270-4
Blood Cancer J. 2025 Mar 28. 15(1): 48

Carfilzomib prescribing patterns and outcomes for relapsed or refractory multiple myeloma: a real-world analysis.

Sharlene Dong, Rahul Banerjee, Adeel M Khan, Mengru Wang, Xiaoliang Wang, Anosheh Afghahi, Aimaz Afrough, Murali Janakiram, Bo Wang, Andrew J Cowan, Adam S Sperling, Larry D Anderson, S Vincent Rajkumar, Gurbakhash Kaur.

Despite the widespread use of carfilzomib (K) in relapsed/refractory multiple myeloma (RRMM), there is no consensus on optimal K dose in milligrams per square meter (mg/m2) or dosing schedule. We assessed three modern K prescribing patterns in RRMM using a large United States electronic health record-derived database. Our final cohort (n = 486) included 136 patients (28.0%) who received K 56 mg/m2 once weekly (K56-1x), 86 (17.7%) who received 56 mg/m2 twice weekly (K56-2x), and 264 (54.3%) who received 70 mg/m2 once weekly (K70-1x). Between 2016 and 2023, once-weekly dosing became more common: K70-1x proportions changed from 21.1% in 2016 to 50.6% in 2023, K56-1x from 15.8% to 37.0%, and K56-2x from 63.2% to 12.3%. Median progression-free survival was 13.0 months [95% confidence interval (CI) 11.2-20.7] for K56-1x, 13.2 months (95% CI 9.0-28.1 months) for K56-2x, and 10.9 months (95% CI 9.9-15.3 months) for K70-1x; these differences were not statistically significant (log-rank p = 0.46). Rates of heart failure was comparable (<5% in all cohorts). In summary, our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of time toxicity from frequent infusions.

DOI: https://doi.org/10.1038/s41408-025-01256-2
Haematologica. 2025 Apr 03.

A phase IIb study of selinexor in combination with daratumumab in patients with daratumumab-refractory multiple myeloma.

Noa Biran, Eli Zolotov, David Vesole, Harsh Parmar, Pooja Phull, Kimberley Doucette, Patrick Roney, Jaeil Ahn, Rena Feinman, Joshua Zenreich, Palka Anand, Monique Pace, Alexandra Della Pia, Bianca DeAgresta, Lisa Biamonte, Adolfo Aleman, Ella Rutanen, Aimee Chappell, Susan Kumka, David S Siegel.

Not available.

DOI: https://doi.org/10.3324/haematol.2024.287053
Blood. 2025 Mar 31. pii: blood.2024027117. [Epub ahead of print]

Efficacy of a Novel BCL-xL Degrader, DT2216, in Preclinical Models of JAK2-mutated Post-MPN AML.

Zhe Wang, Anna Skwarska, Gowri Poigaialwar, Sovira Chaudhry, Alba Rodriguez-Meira, Pinpin Sui, Emmanuel Olivier, Yannan Jia, Varun Gupta, Warren Fiskus, Cassandra L Ramage, Guangrong Zheng, Alexandra Schurer, Kira Gritsman, Eirini P Papapetrou, Kapil N Bhalla, Daohong Zhou, Adam J Mead, Raajit K Rampal, Jeffrey W Tyner, Hussein A Abbas, Naveen Pemmaraju, Qi Zhang Tatarata, Marina Y Konopleva.

Acute myeloid leukemia (AML) that evolves from myeloproliferative neoplasm (MPN) is known as post-MPN AML. Current treatments don't significantly extend survival beyond 12 months. BCL-xL has been found to be overexpressed in leucocytes from MPN patients, making it a potential therapeutic target. We investigated the role of BCL-xL in post-MPN AML and tested the efficacy of DT2216, a platelet-sparing BCL-xL proteolysis-targeting chimera (PROTAC), in preclinical models of post-MPN AML. We found that BCL2L1, the gene encoding BCL-xL, is expressed at higher levels in post-MPN AML patients compared to those with de novo AML. Single-cell multi-omics analysis revealed that leukemia cells harboring both MPN-driver and TP53 mutations exhibited higher BCL2L1 expression, elevated scores for leukemia stem cell, megakaryocyte development, and erythroid progenitor than wild-type cells. BH3 profiling confirmed a strong dependence on BCL-xL in post-MPN AML cells. DT2216 alone, or in combination with standard AML/MPN therapies, effectively degraded BCL-xL, reduced the apoptotic threshold, and induced apoptosis in post-MPN AML cells. DT2216 effectively eliminated viable cells in JAK2-mutant AML cell lines, induced pluripotent stem cell-derived hematopoietic progenitor cells (iPSC-HPCs), primary samples, and reduced tumor burden in cell line-derived xenograft model in vivo by degrading BCL-xL. DT2216, either as a single agent or in combination with azacytidine, effectively inhibited the clonogenic potential of CD34+ leukemia cells from post-MPN AML patients. In summary, our data indicate that the survival of post-MPN AML is BCL-xL dependent, and DT2216 may offer therapeutic advantage in this high-risk leukemia subset with limited treatment options.

DOI: https://doi.org/10.1182/blood.2024027117
Blood Cancer J. 2025 Apr 02. 15(1): 52

VEN in combination with 10-day DEC in newly diagnosed elderly or relapsed/refractory acute myeloid leukemia, and high-risk myelodysplastic syndrome: long term follow-up of a phase 2 trial.

Mahesh Swaminathan, Courtney D DiNardo, Abhishek Maiti, Naveen Pemmaraju, Maro Ohanian, Navel G Daver, Guillermo Garcia-Manero, Ghayas C Issa, Gautam Borthakur, Farhad Ravandi, Guillermo Montalban-Bravo, Tapan M Kadia, Yesid Alvarado, Elias J Jabbour, Nicholas J Short, William G Wierda, Nitin Jain, Steven M Kornblau, Lucia Masarova, Sherry A Pierce, Wei Qiao, Jing Ning, Hagop Kantarjian, Marina Y Konopleva.

DOI: https://doi.org/10.1038/s41408-025-01265-1