Hematological Oncology最新文献

Introduction: UNCOVER is a blood cancer health data research programme that utilises the National Cancer Registration Dataset (NCRD). NCRD includes information on all patients diagnosed with all types of cancer in all NHS institutions in England (Int J Epidemiol 2020; 49(1):16–16h).

Methods: NCRD data was obtained for all patients in England diagnosed with any type of blood cancer between Jan 2014 and Dec 2021. Patients with newly diagnosed follicular lymphoma (FL) were identified using ICD-O-3 codes 96953, 96913, 96983, and 96903. Crude and adjusted incidence rate ratios (IRR) were estimated and compared between groups using multivariable Poisson regression, and calendar time trends were assessed. Overall survival (OS), cause-specific and relative survival was assessed using K-M methods and multivariable Cox regression, Fine-Gray and Pohar-Perme models, respectively. All models were adjusted for age, gender, index of multiple deprivation (IMD) quintile and government region, while Cox and Fine-Gray models were also adjusted for ethnicity and Charlson co-morbidity index (CCI).

Results: 17561 patients with FL aged 18–99 were identified (demographics in Table 1). Gender (p < 0.001), age (p < 0.001), ethnicity (p < 0.001), region (p < 0.001) and year of diagnosis (p < 0.001) were independently associated with incidence. The adjusted IRR increased with age and was lower in females (0.90), in mixed-race (0.20), Asian (0.43) and black (0.28) people compared to white people, and in all 8 provincial regions compared to London (IRR for North West 0.81). The adjusted IRR for successive calendar years was generally stable but dipped in the first year of the COVID-19 pandemic [2020 vs. 2014; 0.94 (95% CI: 0.89–1.01)]. Survival data were available until July 2023 [median follow-up 4.4 years (IQR: 2.4–6.6)]. 4709 (26.8%) patients died, with 5-year OS 74% (95% CI: 74%–75%) and relative survival 85% (84%–86%). Gender (p < 0.001), age (p < 0.001), ethnicity (p = 0.044), CCI (p < 0.001), IMD (p < 0.001) and year of diagnosis (p = 0.008) were independently associated with OS. The adjusted hazard ratio (HR) increased with age [15.4 (95% CI: 11.6–20.6) for 75–99 vs. 18–44], deprivation [1.47 (1.33–1.61) for IMD1 vs. IMD5] and comorbidity [2.35 (2.09–2.64) for CCI ≥ 4 vs. 0] but was lower in females [0.78 (0.73–0.82)], in black versus white people [0.60 (0.38–0.93)], and in patients diagnosed in 2015 versus 2014 [0.86 (0.78–0.96)].

Conclusion: Our findings shed new light on FL epidemiology and outcomes in England during the period 2014–2021. Even when other variables such as age and comorbidity were taken into account, reported incidence was lower and survival shorter in people living in more deprived areas, identifying a group with significant unmet needs. A significant proportion of patients died of unrelated

Relapsed and refractory (r/r) mature B-NHL in chidlren and adolescents represents an area of unmet cinical need due to the poor prognosis of these patients. Burkitt lymphoma and Diffuse Large B-cell lymphoma are the majority histologies.

Mulitple new immuno-oncology therapies are available or being investigated in adult r/r mature B-NHL. The rarity of childhod and adolescent disease makes evaluation of all of these impossible and a more strategic approach is required.

This lecture will explore the challenges of rational new drug development in this rare disease and highlight the current landscape with an emphasis on an international, transatlantic, academic-industry collaborative, fit-for-filing trial -Glo-BNHL (NCT05991388)

Research funding declaration: CRUK, FKC, Multiple industry partners.

Keywords: non-Hodgkin (Pediatric, Adolescent, and Young Adult); immunotherapy; ongoing trials

Potential sources of conflict of interest:

A. Burke

Other remuneration: Institutional funding from Regeneron, ADCT Therapeutics and BMS for clinical trial

Background: An optimal first-line therapy for Waldenstrom’s Macroglobulinemia (WM) has not been defined. We postulated that combining bendamustine and rituximab (BR) with acalabrutinib will result in deep and durable responses, particularly in high-risk patient subsets.

Methods: The BRAWM clinical trial (NCT04624906) combined BR and acalabrutinib in a one-year, fixed duration treatment course of six 28-day cycles of BR and 365 days of concurrent acalabrutinib. This phase II trial took place at 9 clinical sites across Canada. The primary outcome was combined complete response + very good partial response (CR+VGPR) rate, and secondary outcomes included PFS, OS and Measurable Residual Disease (MRD). Outcomes were assessed for all participants, and for high-risk subsets (MYD88^WT, CXCR4^MUT and TP53^MUT). MRD analyses uses bone marrow (BM) and peripheral blood (PB) samples collected at trial specific time points, assessments being performed by Adaptive Biotechnologies (Seattle, USA) using the clonoSEQ assay. Outcomes were compared between high-risk and non-high risk subsets.

Results: This trial enrolled 63 participants. The median age was 69 years (range 39–85), and 49 (78%) were male, 38% intermediate-risk and 51% high-risk IPSS-WM score. Mutational analysis in 57 participants showed 50 (88%) were MYD88^MUT and 16 (30%) were CXCR4^MUT, 1 was TP53 ^MUT. CR+VGPR occurred in 37/59 participants (62.7%) at cycle 7, 28/45 (62.2%) at cycle 12, and 21/39 (53.8%) at month 18 (Figure 1A). The median follow-up was 18 months (1.4–42.4). Both 24-month OS and PFS were 97.6% (95% CI: 93%–100%), 1 participant died at 15 months unrelated to treatment. On univariate analysis, CXCR4^MUT was not associated with inferior CR+VGPR rate at 1 year (p = 0.10). Grade 3/4 treatment-related adverse events (TRAE) occurred in 31/63 participants during combination therapy, most common being neutropenia (n = 23) and thrombocytopenia (n = 3). During monotherapy, 13/59 participants had a grade 3/4 TRAE, 6 of whom had neutropenia. MRD negativity (threshold of 10⁻⁶) in PB was 82% at cycle 7, 91% at cycle 12 and 71% at month 18. MRD negativity in BM was not as frequent but increased in BM over time (9% at cycle 7, 12% at cycle 12 and 23% at month 18). MRD negativity rates at cycles 7 and 12 were similar in those with and without CXCR4^MUT and MYD88^WT (Figure 1B). Log reductions of MRD in PB and BM in high-risk subsets were also comparable to corresponding non-high risk subsets.

Conclusions: Fixed duration BR and acalabrutinib was effective and well-tolerated. This regimen achieves amongst the highest CR+VGPR rates seen in frontline WM trials. Acknowledging sample size limitations, high-risk sub

In the decade since publication of the Lugano Classification (Cheson et al, J Clin Oncol 2014,32:3059–3068; Barrington et al, J Clin Oncol 2014, 32:3048–3058), major advances in lymphoma therapy and assessment, including metabolic tumor volume (MTV) and circulating tumor DNA (ctDNA) prompted a workshop at the International Conference on Malignant Lymphoma-17 entitled “Lugano Classification: Looking Toward the Future”, to determine whether a revision was warranted and what it should look like. This report summarizes the conclusions of that workshop and a subsequent questionnaire of the participants. It was concluded that, whereas, minor modifications could be made now, the current classification should remain the standard until the clinical benefit of MTV and ctDNA are firmly established and practical considerations demonstrated. An ICML sponsored standing committee will monitor progress and ensure that a revision of the Lugano Classification will be proposed when warranted.

Background: Standard rituximab (R) +lenalidomide (R2) or chemoimmunotherapy is effective in treatment-naïve follicular lymphoma (TN FL) but is associated with Grade 3–4 AE rates > 65% with elderly patients (pts) overrepresented. Golcadomide (Golca) is a potent first-in-class oral Cereblon E3 Ligase Modulator (CELMoD) with dual immunomodulatory and anti-tumor activity 10- to 100-fold enhanced compared to lenalidomide, preferential lymphoid organ distribution and a favourable toxicity profile (Chavez ASH 2024; Amzallag ASH 2024). R-Golca yields responses in 93% relapsed FL. We have demonstrated immune augmentation, safety and efficacy of PD1/PDL1i nivolumab (N) +rituximab, and atezolizumab-obinutuzumab-radiotherapy in TN FL (Chong ASCO 2024; Barraclough Blood Adv 2025). We describe here the interim analysis of a randomised phase II study of R-Golca +/- N in stage II-IV, Grade 1–3A TN FL. (Chong ASCO 2024)

Methods: TOP-FLOR (NCT05788081) is an investigator-led multicentre randomised open label umbrella Baysian Optimal Phase II trial in TN FL. Up to 40pts will be randomised 1:1 to receive 8 cycles of induction therapy Q4W: R (375 mg/m² IV, D1), Golca (0.4 mg p.o daily, D1–14) +/- N (480 mg IV, D1) and 2 years of R maintenance (Q12W). The primary endpoint is rate of Complete Metabolic Response (CMR) in the absence of cessation due to prohibitive toxicity (CTCAE V5.0) following induction. Interim efficacy analysis (PET/CT Lugano response) in the first 22 pts was pre-planned, with a predefined futility threshold of 7/11 CMR (63.6%) in each arm.

Results: The interim analysis included 22 enrolled pts (11 per arm). Median age was 64.5y (range 49–77) with 68% male. CMR rate at the end of induction was 82% (18/22; 95% CI: 60%, 95%), CMR rate by arm in the futility cohort, was: 10/11 (92%) R-Golca and 8/11 (73%) R-Golca+N with 1 permanently ceasing due to Gr4 sepsis in cycle 1, unrelated to therapy and 1 ceasing due to disease progression (Figure 1). Proportion of pts experiencing an AE during induction were: 100% Gr1, 82% Gr2, 64% Gr3, 9% Gr4 (2pt). Most frequent of any grade were infection (77%; 95% CI: 54%–92% [Gr3 14%]), neutrophil count decrease (63%; 95% CI: 40–82% [Gr3+ 92%; plus 2 pt Gr3 febrile neutropenia]; 10pts received G-CSF) and maculo-papular rash (45%; 95% CI: 24%–67%—all in pts who had bactrim & allopurinol which resolved on cessation of allopurinol); 2 pts R-Golca +N arm and 1 pt in the R-Golca arm had Golca dose reduction to 0.3 mg due to adverse events. 18/22 remain on treatment. Interim results reached the threshold for continued recruitment in both arms.

Conclusions: This is the first study to demonstrate that Rituximab-golcadomide +/-nivolumab is a highly effective combination therapy in TN FL with manageable toxicity, most commonly neutropenia and infection. Differences between arms could not be elucidated in this preplanned interim analysis. The study continues recruit