Hematological Oncology最新文献

18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) parameters have shown a significant prognostic role in relapsed/refractory large B-cell lymphoma (LBCL) patients undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. While a substantial body of evidence exists on the prognostic value of PET/CT parameters in peri-CAR T setting, data available on the prognostic value of PET/CT parameters following CAR T-cell therapy failure is lacking. Therefore, we sought to analyze the PET/CT scans of LBCL patients who experienced post-CAR T relapsed/progressive disease and subsequently received salvage therapies. Thirty-three LBCL patients who had PET-CT scans done demonstrating post-CAR T failure and then received salvage therapies [as a first salvage modality: RT alone, nine patients; combined modality therapy (CMT), seven patients; systemic therapy (ST) alone, 17 patients] were analyzed. The median follow-up after CAR T-cell infusion was 11.7 months [interquartile range (IQR): 5.1–24.4 months], and the median follow-up after post-CAR T salvage therapy was 7.3 months (IQR: 2.7–19.1 months). The median timeframe for the PET scan showing post-CAR T failure was 2.4 months (IQR: 0.96–5.0 months). On univariable analysis from salvage therapy start date, high metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with inferior overall survival (OS) (Hazard ratio –HR = 8.4, p < 0.0001; HR = 3.2, p = 0.01, respectively). High MTV was associated with a non-significant trend of inferior progression-free survival (PFS) (HR = 3.5, p = 0.09). High maximum standardized uptake value (SUVmax) was not associated with inferior OS or inferior PFS. On multivariable analysis from salvage therapy start date, high MTV (HR = 4.6, 95% CI: 1.5–14.3, p = 0.009) was identified to be an independent prognostic factor for inferior OS. High International Prognostic Index (IPI) (≥ 3) at the time of salvage therapy (HR = 2.5, 95% CI: 1.1–5.6, p = 0.02) was significantly associated with inferior PFS. Our study shows that semiquantitative PET/CT metrics, especially MTV, are significant prognostic indicators of overall survival in this highly refractory population after CAR T-cell therapy failure, potentially refining prognostic and treatment approaches beyond conventional parameters like IPI.

As indolent non-Hodgkin's lymphomas (iNHLs) are very radiosensitive, radiation treatment (RT) has been established as an essential curative and palliative modality for early and advanced stages of the disease. Several studies have explored the role of very low-dose RT for palliation in indolent non-Hodgkin's lymphomas, demonstrating that this approach can lead to high rates of local control, and thereby, help improve the quality of life for these patients. While the most common schedule of very low-dose RT used in the palliative setting is 4Gy in 2 fractions, which was established in the landmark FoRT trial, this requires patients to be available for two RT sessions, increasing the financial and opportunity costs for the patient. Currently, data regarding the use of a single fraction of very low-dose RT (4Gy) for treating iNHLs in the palliative setting is still lacking. In this viewpoint, we aim to draw attention to this approach, where we emphasize the need for further exploration of the single-dose fractionation schedule as a non-toxic, simple, and easy treatment approach for iNHLs, which would inform future clinical trials to investigate this dose/fractionation.

Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX trial. However, real-world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola-R-CHP versus R-CHOP outcomes in routine clinical practice in China. This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of polatuzumab vedotin up until February 2024. A total of 600 eligible patients from 6 centers were identified, 131 receiving Pola-R-CHP and 469 R-CHOP. After 1:2 propensity score matching, 128 pairs were obtained for further survival and prognosis analysis. With a median follow-up of 12.8 months, 12-month progression-free survival (PFS) was numerically higher with Pola-R-CHP versus R-CHOP (90.3% vs. 84.1%, p = 0.18). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG ≥ 2, extranodal involvement ≥ 2 and non-GCB group. The complete response rate of the Pola-R-CHP group was higher than that of the RCHOP group (86.8% vs. 79.7%; p = 0.09), but there was no statistical difference. Safety profiles were comparable, with no new concerns. Among 128 patients treated with Pola-R-CHP, 96 underwent gene sequencing analysis: MCD (25.0%), EZB (13.5%), combined subtype (12.5%), ST2 (9.4%), and other/unclassifiable subtype (30.2%). The most common mutations (> 25% of cases) were PIM1, TP53, BCL-6, KMT2D, SOCS1, BCL-2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected populations. While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.

Secondary acute myeloid leukemia (s-AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG-Ida) have been tested to improve results. More recently, CPX-351 resulted superior to conventional 3 + 7 in s-AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG-Ida or CPX-351. Subgroup analysis revealed better overall survival (OS) with CPX-351 in patients with MDS-related gene mutations. Unfortunately, minimal residual disease (MRD) was evaluated only in a minority of patients. The aim of this study was to further disclose the mechanisms of higher efficacy of CPX-351 in s-AML, with a focus on MRD. We analyzed 183 consecutive s-AML elderly patients (median age 69, range 60–77) treated with CPX-351 (n = 82) or receiving FLAG-Ida (n = 101). Complete remission (CR) rate and MRD negativity probability were higher among patients receiving CPX-351 (MRD negative CR rate of 40/64, 62.5%, compared to 25/55, 45% in patients who received FLAG-Ida, p < 0.05). Extra-hematological toxicity was lower in CPX-351 arm, and 30 days mortality was 3.6% and 8% in patients receiving CPX-351 or FLAG-Ida, respectively. Notably, 21/64 (32.8%) CR patients treated with CPX 351 underwent allogeneic stem cell transplantation (HSCT), compared to 5/55 with FLAG-Ida (9%, p < 0.05). Overall, CPX-351 treatment resulted in higher OS (median OS 17.7 vs. 11.2 months with FLAG-Ida, p < 0.05). The better outcome of CPX-351 compared to FLAG-Ida in our cohort may be explained by a greater probability of MRD negativity, alongside with an improved tolerance, enabling more s-AML patients to undergo HSCT.