Hematological Oncology最新文献

Follicular lymphoma (FL) is an indolent disease characterized by multiple relapses and eventual refractoriness to therapy. Despite advancements in therapeutic approaches, FL treatment algorithm and management remain not well-established, necessitating both ongoing research into novel therapeutic strategies and in stating patient journey. We propose a comprehensive overview of current standard treatments for relapsed or refractory (R/R) FL, including chemoimmunotherapy and stem cell transplantation, and insights into emerging therapies such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies. We discuss the efficacy and safety profiles of these innovative treatments, their integration into the therapy armamentarium, and the potential they hold in altering the natural history of FL. Additionally, we propose a therapeutic flow depending on POD24 (i.e., progression of disease within 24 months), transformed disease, early relapse and fast/low progression, with the aim to provide a useful tool to all physicians dealing with this disease for achieving sustained remission and improving the quality of life in patients with R/R FL.

Over the past 2 decades, advancements in follicular lymphoma (FL) treatment, particularly with anti-CD20 antibodies, have significantly improved patient survival. However, a subset of FL patients experiences early relapse and progression within 24 months (POD24) after first line treatment, which is a sign of poor prognosis. Current guidelines recommend various second-line treatments, but there is no consensus on an optimal treatment sequence for relapsed/refractory (r/r) FL. Moreover, despite available treatments, reduced survival after second-line therapies and diminishing responses with each relapse highlight the unmet need for more effective options. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment for r/r FL beyond 2^nd line therapy, with three FDA/EMA-approved therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) showing high efficacy and manageable side effects. However, challenges remain in determining which patients will benefit most from CAR-T, especially given its high cost, safety concerns, and logistical barriers. A consensus study was conducted to guide CAR-T patient selection and treatment sequencing for patients in 3rd line or beyond. Key findings suggest that younger patients, those with high disease burden or poor first-line responses, should be prioritized for CAR-T. Additionally, CAR-T is recommended as a third-line option for patients with POD24, double refractoriness (failure to respond to two subsequent lines of immunochemotherapy), or early autologous stem cell transplant failure. The study underscores the importance of early assessment of treatment response, careful second-line therapy selection, and patient adherence to ensure optimal outcomes. The results, based on expert consensus, support CAR-T therapy as a viable option for r/r FL patients, offering hope for durable remissions in this challenging cohort.

J. Yang, Z. Wang, K. Wu, et al. Isocitrate Dehydrogenase 2 Mutation Promotes Cytarabine Resistance in Acute Myeloid Leukemia by Warburg Effect. Hematological Oncology 42, no. 6 (2024): e3316. https://doi.org/10.1002/hon.3316.

In the article, there were errors in Figures 1, 2 and 3. The representative flow cytometry results for HL-60 cell apoptosis, such as (KD-IHD2 group in Figure 1, WT + Enasidendb group in Figure 2, and IDH2 mutated group in Figure 3) were inadvertently used from different batches.

The corrected figures are shown below. The authors confirmed that these corrections do not affect or alter the conclusion of the article.

In this retrospective analysis on patients treated with CAR T-cells at our center, we report on the use of radiotherapy in this setting. Our real-world cohort of 90 patients with aggressive lymphomas was treated with CARs from 2019 until December 2022. We found that the outcome of a localized relapse after CARs treated with radiotherapy was comparable to patients without a relapse. With the knowledge from the collected real-world data, we should launch prospective clinical trials to further improve the use of radiotherapy, and overall the efficacy of CAR T-cell therapies for patients with aggressive lymphomas.

Late cardiac toxicity after radiation therapy and/or systemic therapy with anthracyclines for lymphomas is a serious concern. To estimate the risks with different treatment combinations, reliable estimates of the dose-response relationships are needed. We performed a literature-based regression analysis of long-term cardiac events after lymphoma treatment. The objective was to identify dose-response relationships for anthracycline and radiotherapy regarding congestive heart failure (CHF), ischemic heart disease (IHD), and valvular heart disease (VHD). We included papers published January 2000-December 2022 with data on long term cardiac outcomes in lymphoma patients, radiation doses to the heart, and anthracycline doses. Papers without dose/response information were excluded. We identified six eligible papers including 22,916 patients. The excess relative risk (ERR) of CHF for anthracyclines per 100 mg/m2 (corresponding to 2 cycles of ABVD or CHOP chemotherapy) was 92% (CI: 74%–101%), and for radiotherapy per Gray (Gy) of mean heart dose it was 6.1% (CI: 4.4%–7.6%). Corresponding numbers for the other endpoints were: IHD: No effect of anthracyclines, ERR = 4.4%/Gy (CI: 2.7%–6.1%) and VHD: ERR = 25%/100 mg/m2 (CI: 13%–37%) and ERR = 10%/Gy (CI: 6%–13%). Data agree with a linear no threshold dose-response relationship for related endpoints, that is, there are no “safe” lower doses of either anthracyclines or radiotherapy. Late cardiac toxicity risks for all three endpoints can be assessed in each patient by a combined estimate from the cumulative doses of anthracyclines and radiation to the heart. This estimate can guide future treatment allocation in lymphoma patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy. More than half of DLBCL patients achieve long-term remission after treatment, but a third relapse after conventional Rituximab (R)-based chemotherapy regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Cancer cells are exposed to chronic replication stress, which impedes the duplication of their genome. Functional DNA repair pathways are therefore important for the survival of cancer cells. This dependence can be exploited therapeutically to hamper repair of the intrinsic DNA damage occurring during replication or to exacerbate DNA damage induced by chemotherapy. Using CRISPR-Cas9 screening, we identified CHEK1, WEE1, ATR and RAD51 DNA repair factors as essential genes in DLBCL cells. According to these results, we investigated the effect of small molecules targeting DNA replication stress and DNA repair mechanisms, alone or in combination with the R-CHOP genotoxic agents, cyclophosphamide and doxorubicin. Applying a standard threshold of 2 SDs below the IC50 of the genotoxic agent alone, a total of 3 synthetic lethal combinations have been identified including cyclophosphamide with CHK1/2 inhibitor, cyclophosphamide and ATR inhibitor and doxorubicin with DNAPK inhibitor. Co-treatment with these molecules led to cell death, DNA damage induction and cell cycle arrest in DLBCL cells more efficiently than genotoxic agents alone. These data have been validated using primary DLBCL cells from patients. Our results open new perspectives for therapeutic approaches exploiting the synthetic lethality of genotoxic agents with DNA repair inhibitors to improve the therapeutic outcome of patients with DLBCL.