bims-hemali 2025-02-23 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–02–23
twelve papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Treatment-free remission in nontransplanted patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial.
Reduced-dose chemotherapy followed by blinatumomab for newly diagnosed philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia: a propensity-matched comparison with hyper-CVAD.
Is t(11;14) Always a Standard-Risk Cytogenetic Abnormality? Results From GEM05MENOS65 and GEM2012 PETHEMA/GEM Transplantation Trials.
Preconditioning intervention before allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia.
A Case Series and Literature Review on Zanubrutinib Therapy for the Treatment of Relapsed/Refractory Immune Thrombocytopenia.
Phase 1 study of lintuzumab-Ac225 combined with CLAG-M salvage therapy in relapsed/refractory acute myeloid leukemia.
Comparison of outcomes in postinduction strategies for primary central nervous system lymphoma: a Mayo Clinic experience.
Thrombotic events in patients with multiple myeloma and their impact on overall survival.
Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with anti-CD19 CAR-T cells: CARTHYM, a study from the French national DESCAR-T registry.
A belt-and-suspenders approach to PNH.
Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma.

Cancer. 2025 Mar 01. 131(5): e35773

Treatment-free remission in nontransplanted patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Eitan Kugler, Hagop Kantarjian, Elias Jabbour, Niranjan Khaire, Nicholas J Short, Tapan M Kadia, Fadi G Haddad, Koji Sasaki, Rashmi Kanagal Shamanna, Rebecca Garris, Farhad Ravandi, Nitin Jain.

   BACKGROUND: The BCR::ABL1 tyrosine kinase inhibitors (TKIs) have significantly improved the outcomes of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, the optimal duration of TKI therapy in patients who achieve a complete molecular response (CMR; undetectable BCR::ABL1 transcripts) and who do not undergo allogeneic stem cell transplantation (allo-SCT) remains undefined.
METHODS: The authors conducted a retrospective analysis of patients with Ph-positive ALL in first complete remission who achieved a CMR and discontinued TKI therapy, most commonly due to treatment-related side effects.
RESULTS: In total, 14 patients were identified. The regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine was the primary backbone chemotherapy and was received by 12 patients (86%) combined with either imatinib (14%), dasatinib (43%), or ponatinib (29%) during induction. Two patients received blinatumomab and ponatinib. The median duration of TKI therapy was 60 months. The median CMR duration before TKI discontinuation was 46.1 months (range, 2.7-121.3 months). After a median follow-up of 42.5 months from TKI discontinuation, three patients (21%) experienced relapse (two molecular, one morphologic), whereas 11 patients (79%) maintained treatment-free remission. The median time to relapse was 6.4 months (range, 4-16 months), and two of three relapsed patients regained CMR after resuming TKI therapy. Importantly, none of the six patients with a CMR duration >48 months before TKI discontinuation relapsed.
CONCLUSIONS: The current findings suggest that TKI discontinuation may be safe for highly selected patients with Ph-positive ALL in first complete remission who maintain CMR for at least 48 months. Larger studies are needed to confirm these findings.

Keywords:  Philadelphia chromosome‐positive (Ph‐positive); acute lymphoblastic leukemia (ALL); treatment‐free remission (TFR); tyrosine kinase inhibitors

DOI:  https://doi.org/10.1002/cncr.35773
EClinicalMedicine. 2025 Feb;80 103078

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with high-dose methotrexate plus intrathecal chemotherapy for newly diagnosed intravascular large B-cell lymphoma (PRIMEUR-IVL): long-term results of a multicentre, single-arm, phase 2 trial.

Kazuyuki Shimada, Motoko Yamaguchi, Yachiyo Kuwatsuka, Kosei Matsue, Keijiro Sato, Shigeru Kusumoto, Hirokazu Nagai, Jun Takizawa, Noriko Fukuhara, Koji Nagafuji, Kana Miyazaki, Eiichi Ohtsuka, Akinao Okamoto, Yasumasa Sugita, Toshiki Uchida, Satoshi Kayukawa, Atsushi Wake, Daisuke Ennishi, Yukio Kondo, Akiko Meguro, Yoshihiro Kin, Yosuke Minami, Daigo Hashimoto, Takahiro Nishiyama, Satoko Shimada, Yasufumi Masaki, Masataka Okamoto, Yoshiko Atsuta, Hitoshi Kiyoi, Ritsuro Suzuki, Shigeo Nakamura, Tomohiro Kinoshita.

   Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma for which prognosis is typically poor without a timely diagnosis. To explore the safety and efficacy of standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted a multicentre, single-arm, phase 2 trial in untreated IVLBCL patients without CNS involvement at diagnosis (PRIMEUR-IVL). In the primary analysis, the PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence (3%) of secondary CNS involvement (sCNSi).
Methods: We present a prespecified final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and cumulative incidence of sCNSi. Participants were enrolled between June 2011 and July 2016, and the data cutoff date for the final analysis was 16 November 2021. The trial was registered in the UMIN Clinical Trial Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165).
Findings: With a median follow-up of 7.1 years (interquartile range 5.6-8.7), 5-year PFS in all 37 eligible patients was 68% (95% confidence interval [CI] 50%-80%) and OS was 78% (95% CI 61%-89%). No additional sCNSi was observed after the primary analysis. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). Eight deaths occurred during the observation period after enrolment, due to primary disease (n = 6), sepsis (n = 1) and unknown sudden death (n = 1).
Interpretation: Long-term follow-up data demonstrated durable response for PFS and OS, and low cumulative incidence of sCNSi, indicating the efficacy of standard chemotherapy combined with CNS-directed therapy for untreated IVLBCL patients.
Funding: This study received financial support from the Japan Agency for Medical Research and Development, Center for Supporting Hematology-Oncology Studies, and National Cancer Center.

Keywords:  Central nervous system-directed therapy; Intravascular large B-Cell lymphoma; R-CHOP; Secondary central nervous system involvement

DOI:  https://doi.org/10.1016/j.eclinm.2025.103078
Discov Oncol. 2025 Feb 21. 16(1): 223

Reduced-dose chemotherapy followed by blinatumomab for newly diagnosed philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia: a propensity-matched comparison with hyper-CVAD.

Jing Lu, Yu Zhu, Huiying Qiu, Ying Wang, Xin Zhou, Haiping Dai, Xuzhang Lu, Bin Gu, Ming Hong, Miao Miao, Ruinan Lu, Jun Wang, Qian Wu, Mengxing Xue, Yun Wang, Ailing Deng, Yaoyao Shen, Yin Liu, Xueqing Dou, Yutian Lei, Xiaofei Yang, Suning Chen.

   BACKGROUND: Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative BCP-ALL) accounts for a significant portion of adult cases. Blinatumomab, a bispecific T-cell engager, has shown efficacy in relapsed or refractory BCP-ALL, but its role in induction therapy with reduced-dose chemotherapy is being explored.
METHODS: In this retrospective study, 35 newly diagnosed Ph-negative BCP-ALL patients received reduced-dose chemotherapy followed by two weeks of blinatumomab (RDC-Blinatumomab-2W) as part of our previous clinical trial. These patients were compared with a propensity score-matched historical control group of 35 patients treated with the hyper-CVAD regimen. The primary endpoint was composite complete remission (CRc); secondary endpoints included minimal residual disease (MRD) negativity, adverse events, and survival outcomes.
RESULTS: After matching, both groups had 17 patients (49%) with poor-risk genetic aberrations. The RDC-Blinatumomab-2W group achieved higher CRc rates compared to controls (94% vs. 63%, p = 0.0074) and greater MRD negativity (86% vs. 43%, p = 0.0015). They experienced fewer Grade 3-4 thrombocytopenia cases (62% vs. 89%, p = 0.012), fewer serious infections (23% vs. 54%, p = 0.019), and higher 1-year overall survival rates (97.1% vs. 58.9%, p < 0.001). The 1-year progression-free survival was also superior in the RDC-Blinatumomab-2W group (82.2% vs. 44.6%, p = 0.002).
CONCLUSION: Reduced-dose chemotherapy followed by blinatumomab improves remission rates, MRD negativity, and survival while reducing adverse events in newly diagnosed Ph-negative BCP-ALL patients compared to hyper-CVAD. This regimen offers a safer and more effective induction therapy option, warranting further investigation in larger trials.
CLINICALTRIALS:
GOV IDENTIFIER: NCT05557110; registered on September 8, 2022.

Keywords:  B-cell precursor acute lymphoblastic leukemia; Blinatumomab; Induction therapy; Philadelphia chromosome-negative

DOI:  https://doi.org/10.1007/s12672-025-01968-8
Clin Lymphoma Myeloma Leuk. 2025 Jan 25. pii: S2152-2650(25)00024-2. [Epub ahead of print]

Is t(11;14) Always a Standard-Risk Cytogenetic Abnormality? Results From GEM05MENOS65 and GEM2012 PETHEMA/GEM Transplantation Trials.

PETHEMA/GEM group

   PURPOSE: Recent studies describe inferior outcomes in newly diagnosed multiple myeloma (NDMM) patients with t(11;14) treated with novel agents.
MATERIALS AND METHODS: We analyzed 240 NDMM transplant eligible (TE) patients who received triplet induction regimen in the GEM05MENOS65 (bortezomib, thalidomide and dexamethasone - VTD) and GEM2012 (bortezomib, lenalidomide and dexamethasone - VRD) clinical trials.
RESULTS: t(11;14) and standard risk (SR) non-t(11;14) were prevalent in 51 (21%) and 189 (79%) patients, respectively. Patients with t(11;14) treated with VTD had a lower overall response rate (ORR) (84% vs. 97%, P = .044) and lower negative minimal residual disease (MRD) (7.7% vs 35.1%, P = .049) after induction, as compared to SR non-t(11;14), while there were no differences in ORR (87% vs. 89%) or negative MRD (13.2% vs. 24.4%, P = .2) for these 2 subgroups in patients treated with VRD. The presence of t(11;14) impacted negatively on PFS in patients with VTD (hazard ratio 2.70; P = .005), while no differences were observed in those treated with VRD.
CONCLUSION: TE NDMM patients harboring t(11;14) had an inferior outcome compared with SR patients when receiving induction therapy with VTD while no differences were observed when receiving a lenalidomide containing regimen.

Keywords:  Cytogenetics; Induction; Multiple myeloma; Transplant; t(11;14)

DOI:  https://doi.org/10.1016/j.clml.2025.01.014
Exp Hematol. 2025 Feb 12. pii: S0301-472X(25)00037-2. [Epub ahead of print] 104746

Preconditioning intervention before allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia.

Takayoshi Tachibana, Akihiko Izumi, Shota Arai, Takaaki Takeda, Natsuki Hirose, Yotaro Tamai, Shuku Sato, Chizuko Hashimoto, Katsumichi Fujimaki, Ryuji Ishii, Hirotaka Sakai, Etsuko Yamazaki, Yasuyuki Inoue, Masatsugu Tanaka, Hideaki Nakajima.

The outcomes of patients with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HCT) remain poor despite many attempts at developing therapeutic strategies. Preconditioning interventions (PCIs) have been applied to patients with high-risk AML to reduce the disease burden before starting the conditioning regimen. A single-center retrospective study was performed to evaluate the safety and efficacy of PCI in allograft patients with high-risk AML. Thirty-three patients with a median age of 57 (16-70) years were included to the entire cohort. Among various PCI regimens, venetoclax plus azacitidine was administered to 12 patients. The median drug withdrawal day was 0 days (range, 0-12) for low-intensity PCIs and 12 days (range, 8-14) for high-intensity PCIs. With no grade 3 nonhematological adverse events during PCIs, the median blast fraction in the bone marrow before and after PCIs decreased from 12.4% to 2.1% (p = 0.001). Excluding three patients with early complication-related deaths, all 30 patients achieved engraftment within a median of 30 days. The overall survival, cumulative incidence of relapse, and nonrelapse mortality (NRM) rates at 2 years were 67.1%, 23.9%, and 8.8%, respectively. The cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) at 100 days and chronic GVHD at 2 years were 32.4% and 23.5%, respectively. PCI may be safe and effective in promoting engraftment and reducing the risk of disease relapse without increasing the risk of NRM. Further clinical trials are warranted to establish appropriate PCI strategies.

DOI: https://doi.org/10.1016/j.exphem.2025.104746
Cancer Rep (Hoboken). 2025 Feb;8(2): e70152

A Case Series and Literature Review on Zanubrutinib Therapy for the Treatment of Relapsed/Refractory Immune Thrombocytopenia.

Bingjie Ding, Mengjuan Li, Liu Liu, Xuewen Song, Yuanyuan Zhang, Ao Xia, Jingyuan Liu, Hu Zhou.

   BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterised by low platelet count. Treatment discontinuation or heterogeneity in the pathogenesis of ITP heightens the occurrence of relapsed or refractory ITP. Bruton's tyrosine kinase (BTK) has emerged as a promising target for autoimmune disorders.
CASE: In this case series, we have explored the efficacy and safety of Bruton's tyrosine kinase inhibitors (BTKi) in treating relapsed/refractory ITP, by retrospective analysis of the diagnostic history and efficacy of four patients with relapsed/refractory ITP who attended the Affiliated Cancer Hospital of Zhengzhou University and were treated with BTKi. All four patients received > 4 lines of ITP treatment and did not respond to splenectomy or other interventions before and after treatment with BTK inhibitor. After adjusting to the treatment with BTKi, one patient achieved a complete response, and two patients achieved a partial response. All three patients achieved sustained remission with platelet counts of > 50 × 109/L maintained for 1045, 390 and 334 days, respectively. Another patient died of intracranial haemorrhage due to a decline in the platelet count after discontinuation of the drug, and the duration of sustained remission before discontinuation of the drug was 120 days. Four patients had no significant abnormalities in the functions of the liver and kidney monitored during the treatment period.
CONCLUSION: For patients with relapsed/refractory ITP, BTK inhibitor therapy can be considered as an option, with promising preliminary efficacy and safety. However, more clinical trials are needed to verify the exact data.

Keywords:  BTK inhibitor; immune thrombocytopenia; refractory; relapse

DOI:  https://doi.org/10.1002/cnr2.70152
Leukemia. 2025 Feb 15.

Phase 1 study of lintuzumab-Ac225 combined with CLAG-M salvage therapy in relapsed/refractory acute myeloid leukemia.

Sameem M Abedin, Guru Subramanian Guru Murthy, Mehdi Hamadani, Laura C Michaelis, Karen-Sue Carlson, Lyndsey Runaas, Katelyn Gauger, Avinash G Desai, Mary M Chen, Kate L Li, Mojisola Rotibi, Umar Syed, Madhuri Vusirikala, Alexandra Harrington, Ehab L Atallah.

Lintuzumab-Ac255 is a humanized anti-CD33 antibody linked to Actinium-225 delivering high-energy alpha-particles to leukemia cells, inciting double-strand DNA breaks and cell death. This phase 1 study assessed the safety and efficacy of lintuzumab-Ac225 after CLAG-M salvage therapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML). Primary objectives were determination of maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and safety. Using a 3 + 3 dose-escalation design, 21 patients were enrolled sequentially into 4 cohorts to receive a lintuzumab-Ac225 infusion (0.25-1.0 µCi/kg) 7 ( + 2) days after CLAG-M (days 1-6); 5 additional patients received the RP2D. Of evaluable patients, 86.7% had high-risk disease. The MTD and RP2D was 0.75 µCi/kg. Common grade 3/4 adverse events were febrile neutropenia (65.4%) and decreased white blood cells (50%). The composite complete remission (CRc) rates (CR/CRi) were 56.6% overall, 50% in patients with mutated TP53, and 38.5% in prior venetoclax-treated patients. Measurable residual disease (MRD)-negativity was achieved in 8 of 12 responders. Among all patients (n = 26), estimated 2-year OS was 23.1% (95% CI, 9.4-40.3) and estimated 1-year PFS was 30.8% (95% CI, 14.6-48.5). Lintuzumab-Ac225 plus CLAG-M was well tolerated with expected, manageable toxicities, while yielding deep and meaningful responses in high-risk R/R AML patients.

DOI: https://doi.org/10.1038/s41375-025-02528-3
Blood Adv. 2025 Feb 25. 9(4): 924-932

Comparison of outcomes in postinduction strategies for primary central nervous system lymphoma: a Mayo Clinic experience.

Steven R Hwang, Richard C Godby, Brianna J Negaard, Raphael Mwangi, Adrienne N Nedved, Jason N Barreto, Ivana N Micallef, Stephen M Ansell, Luis Porrata, Urshila Durani, Gita Thanarajasingam, Thomas M Habermann, Matthew J Maurer, Patrick B Johnston, Arushi Khurana.

ABSTRACT: Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma involving the brain, cerebrospinal fluid, or retina/vitreous without systemic involvement. Induction with high-dose methotrexate (HD-MTX) followed by consolidation with autologous stem cell transplant (auto-SCT) has become the standard treatment paradigm for most patients. However, limited data are available regarding the efficacy of a maintenance approach with HD-MTX. Herein, we retrospectively reviewed the characteristics and outcomes of 148 patients diagnosed with PCNSL between October 2010 and June 2022, who underwent HD-MTX-based induction therapy followed by either auto-SCT consolidation (n = 70) or HD-MTX maintenance therapy (n = 37). At a median follow-up time of 4.5 years, the progression-free survival (PFS) was 8.3 years and the overall survival (OS) was not reached. Compared to patients who underwent auto-SCT, patients who received maintenance HD-MTX had a higher median age at diagnosis of 72 vs 62 years and a trend toward higher proportion of patients being Eastern Cooperative Oncology Group 2 or higher (41% vs 29%). At 5-years postinduction treatment initiation, the PFS rates in the auto-SCT cohort and HD-MTX maintenance cohort were 74.6% and 72.6%, respectively, and the OS rates were 76.0% and 82.4%, respectively. Overall, there was no significant difference in PFS or OS based on postinduction management strategy. Our data suggest that maintenance HD-MTX may be a reasonable, time-limited treatment strategy for patients with PCNSL responding to initial induction therapy.

DOI: https://doi.org/10.1182/bloodadvances.2024014073
Hematology. 2025 Dec;30(1): 2464316

Thrombotic events in patients with multiple myeloma and their impact on overall survival.

Haimin Chen, Ying Zhang, Zhenzhen Wang, Lixia Wu, Xichang Fei, Wei Wei, Rong Peng, Xiaoling Chen, Haotian Shi, Nian Zhou, Wenjun Yu, Wenhao Zhao, Fan Zhou.

   OBJECTIVE: Thrombotic events (TEs) are common and severe complications of newly diagnosed multiple myeloma (NDMM). However, the impact of thrombosis on the survival of myeloma patients remains controversial. The aim of our study was to identify independent high-risk factors for thrombosis as well as to explore the association between the incidence of TEs and survival in patients with NDMM.
METHODS: We analyzed the clinical characteristics, laboratory results, and survival information of 181 patients with NDMM who were treated at Shanghai Jing'an District Zhabei Central Hospital between July 2020 and March 2024.
RESULTS: Twenty patients (11.0%) developed TEs, including 15 cases (8.28%) of venous thrombosis and 5 cases (2.76%) of arterial thrombosis. Patients who developed TEs were significantly older than those who did not develop TEs (64 vs. 70 years, p = 0.018). The association of TEs with age demonstrated by univariate analysis (HR 1.061, 95% CI 1.010-1.115, p = 0.019) was maintained in multivariable analysis adjusted for interphase fluorescence in situ hybridization, sex, lactate dehydrogenase levels, M protein types, induction regimens, and the International Staging System (HR 1.103, 95% CI 1.018-1.195, p = 0.016). In addition, TEs adversely affect patients' overall survival (27 months vs. not reached, p = 0.01), especially those with arterial thrombosis (16 months vs. not reached, p = 0.06).
CONCLUSION: Age is an independent high-risk factor for TEs in patients with NDMM. The occurrence of TEs shortens the overall survival of myeloma patients, and arterial thrombosis has more severe impact than venous thrombosis. Effective management of thromboprophylaxis is needed for NDMM patients, especially for elderly patients.

Keywords:  Multiple myeloma; overall survival; progression-free survival; thrombosis; thrombotic events

DOI:  https://doi.org/10.1080/16078454.2025.2464316
Hemasphere. 2025 Feb;9(2): e70091

Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with anti-CD19 CAR-T cells: CARTHYM, a study from the French national DESCAR-T registry.

Jean Galtier, Charles Mesguich, Pierre Sesques, Vivien Dupont, Emmanuel Bachy, Roberta Di Blasi, Catherine Thieblemont, Thomas Gastinne, Guillaume Cartron, Gabriel Brisou, François-Xavier Gros, Justine Decroocq, Franck Morschhauser, Marie-Thérèse Rubio, Laurianne Drieu La Rochelle, Fabien Le Bras, Sylvain Carras, Adrien Chauchet, Jacques-Olivier Bay, Magalie Joris, Mickael Loschi, Aline Tanguy-Schmidt, Alexandra Marquet, Vincent Camus, Steven Le Gouill, Roch Houot, Krimo Bouabdallah.

Primary mediastinal B-cell lymphoma (PMBL) is often cured with dose-dense anthracycline-based regimens but the prognosis at relapse or progression remains poor. While anti-CD19 CAR-T cell therapy has dramatically improved outcomes in relapsed or refractory large B-cell lymphoma, far less is known about their efficacy in PMBL. Using the systematic record of all patients treated with CAR-T cells prospectively included in the DESCAR-T registry in France, along with centrally reviewed positon-emission tomography (PET) imaging, we describe the outcomes and key determinants of treatment success in PMBL patients treated over a 6-year period. Among 82 patients infused in the registry we observed a best complete response (CR) rate, 2-year progression-free survival (PFS), and 2-year overall survival (OS) of 68.1%, 57.4%, and 73.8%, respectively. Outcomes were even better for the 62 patients infused with axicabtagene ciloleucel, with best CR rate, 2-year PFS, and 2-year OS reaching 74.5%, 70.4%, and 86.9%, respectively. Achieving a Deauville score of 1-4 or a ΔSUVmax reduction of more than 24% at the 1-month evaluation was associated with excellent outcomes, whereas increased total metabolic tumor volume baseline PET increased the risk of treatment failure. Surprisingly, neither the response to bridging therapy nor the type of bridging therapy (chemotherapy versus immune checkpoint inhibitors) were associated with long-term outcomes. In conclusion, this study confirms that anti-CD19 CAR-T cells as a valid standard-of-care for relapsed and refractory PMBL and highlights key determinants of treatment success.

DOI: https://doi.org/10.1002/hem3.70091
Blood. 2025 Feb 20. 145(8): 785-786

A belt-and-suspenders approach to PNH.

Gloria F Gerber, Robert A Brodsky.

DOI: https://doi.org/10.1182/blood.2024027600
Blood Cancer J. 2025 Feb 18. 15(1): 20

Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma.

Saurabh Zanwar, Dragan Jevremovic, Prashant Kapoor, Horatiu Olteanu, Francis Buadi, Pedro Horna, Wilson Gonsalves, Gregory Otteson, Abiola Bukunmi Bolarinwa, Suzanne Hayman, Nadine Abdallah, Moritz Binder, Joselle Cook, Angela Dispenzieri, David Dingli, Morie A Gertz, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Robert A Kyle, S Vincent Rajkumar, Shaji Kumar.

Risk stratification models based on cytogenetics and disease burden help identify high-risk patients with newly diagnosed multiple myeloma (NDMM). However, some high-risk patients remain undetected. This study evaluated the prognostic utility of the proportion of clonal plasma cells in the S-phase of the cell cycle for NDMM. Patients with active multiple myeloma diagnosed between 01/01/2013 and 01/31/2023 who underwent S-phase assessment were included. The S-phase proportion was calculated by analyzing DNA content between G0/G1 and G2/M peaks. Among 823 patients, 16% (135) had S-phase ≥2% at diagnosis. Patients with S-phase ≥2% exhibited significantly worse median progression-free survival (PFS) of 1.4 years (95% CI: 1.2-1.9) compared to 2.9 years (95% CI: 2.6-3.3) for those with S-phase <2% (HR 1.6, p < 0.0001). Median overall survival (OS) was also significantly lower at 3.9 years (95% CI: 2.9-5.7) versus 9.2 years (95% CI: 7.9-not reached; HR 2.2, p < 0.0001). Multivariate analysis confirmed S-phase ≥2% as an independent predictor of inferior PFS (HR 1.56, p = 0.001) and OS (HR 2, p < 0.0001) after adjusting for R2-ISS risk, age, renal function, and treatment strategies. Among patients with S-phase ≥2%, 53% (68/129) experienced progression-free survival (PFS) under 18 months with upfront therapy. Elevated S-phase was associated with a 2.5-fold higher risk of progression within 18 months [OR 2.55 (95% CI: 1.7-3.7), p < 0.001]. Patients with elevated S-phase but no IMS-high risk had a median OS of 5.7 years (95% CI: 4.7-9.2), similar to the IMS-high risk cohort without elevated S-phase (5.4 years, 95% CI: 4-NR). Those with both elevated S-phase and IMS-high risk had significantly worse OS (3.1 years, 95% CI: 1.6-NR, p = 0.043). These findings suggest that S-phase ≥2% is a powerful, independent prognostic marker for NDMM.

DOI: https://doi.org/10.1038/s41408-025-01232-w