Background
Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The ...sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear.
Methods
In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed.
Results
Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (
p
< 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank
p
= 0.001 and
p
< 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935;
p
= 0.012, and HR 0.620; 95% CI 0.499–0.769;
p
< 0.001, respectively).
Conclusions
Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent immunohistochemical (IHC) high expression ...of MYC and BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155 patients uniformly treated with R-CHOP-like therapies. We performed direct sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6. In multivariate analysis, TP53 mutations in L3 and loop-sheet helix (LSH) associated with a risk ratio (RR) of disease-specific survival (DSS) of 8.779 (p = 0.022) and a RR of disease-free survival (DFS) of 10.498 (p = 0.011). In IHC analysis BCL-2 overexpression was associated with inferior DFS (p = 0.002) and DSS (p = 0.002). DLBCL with BCL-2 and MYC overexpression conferred inferior survival in all patients (DSS, p = 0.038 and DFS, p = 0.011) and in patients with non-GC phenotype (DSS (p = 0.013) and DFS (p = 0.010). Our results imply that in DLBCL, the location of TP53 mutations and IHC analysis of BCL-2 and MYC might have a role in the assessment of prognosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies.
We set out to determine progression-free survival (PFS) after front line, second ...line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1-2 FL between 1997 and 2016 in nine institutions were included.
The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval CI: 7-9.3 years), 4.2 years (95% CI: 2.8-5.6 years) and 2.2 years (95% CI 1.7-2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset.
With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL).
Materials and Methods
We retrospectively studied a large, multicenter, cohort of ...patients with MCL diagnosed between 2000 and 2020 in eight institutions.
Results
536 patients were registered (73% male, median of 70 years). Front‐line treatment was based on high‐dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high‐dose cytarabine‐based, bendamustine‐based and anthracycline‐based therapy. 204 patients received second‐line. Bendamustine‐based treatment was the most common second‐line regimen (36% of patients). The median second‐line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine‐, platinum‐, and high‐dose cytarabine‐based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine‐based therapies in the front‐line and those with front‐line PFS longer than 24 months had a substantially superior sPFS.
Conclusion
Front‐line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second‐line treatment strategies were heterogeneous and the median second‐line PFS was little over 1 year.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Autologous stem cell transplantation (auto-SCT) is an established treatment option in patients with non-Hodgkin lymphoma (NHL). In this prospective multicenter study, the effect of infused blood ...graft cellular composition on post-transplant outcome was analyzed in 129 NHL patients. Higher graft CD34
+
cell content (>2.5 × 10
6
/kg) correlated with better progression-free survival (PFS) (p=.009) and overall survival (OS) (p=.004). Higher graft CD34
+
CD133
+
CD38
-
counts (>0.08 × 10
6
/kg) were also linked with better PFS (p=.03) and OS (p=.004), and these survival benefits retained in multivariate analyses. Higher infused CD3
+
CD4
+
cell count (>37 × 10
6
/kg) predicted better PFS (p=.013) and OS (p=.007) in multivariate analysis. Autograft cellular composition seems to impact outcome in NHL patients. These observations regarding composition of optimal graft in autologous setting should be validated in an independent patient series or in a randomized study.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Follicular T-cell lymphoma (FTCL) is a rare subtype of mature T-cell lymphoma. It was recently recognized as a separate lymphoma entity in the 2017 revised fourth edition of the World Health ...Organization classification. The main goals of the present study were to gain better knowledge of the incidence and histopathological and clinical features of FTCL in Finland. In this study, we reviewed all angioimmunoblastic T-cell (AITL) and peripheral T-cell lymphomas, not otherwise specified, from the patient records in three hospital districts in Finland over a 10-year period, to identify FTCL cases and estimate its incidence. Five patients rediagnosed with FTCL and 34 with AITL were analyzed. Hodgkin/Reed-Sternberg (HRS)-like cells were observed in 24 of the 34 AITL cases and four of the five FTCL cases. We found that the main features that differentiated FTCL from AITL were rosetting of T-cells around HRS-like cells, the absence of clear cells, follicular dendritic cell meshwork and T-cell monoclonality. Our estimated incidence of FTCL is 0.20 per 100,000 people in Finland.
•The incidence of FTCL in Finland.•The differential diagnosis between FTCL and AITL.•Some FTCL cases can be identified with reclassification from AITL and PTCL-NOS diagnostic categories.•T-cell clonality differentiates FTCL from AITL.•The clinical disease presentation of FTCL and AITL seem similar.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although treatment for diffuse large B-cell lymphoma (DLBCL) has taken some notable steps in the 2000s, there are still subgroups of patients suffering from high mortality and relapse rates. To ...further improve treatment outcomes, it is essential to discover new mechanisms of chemotherapy resistance and create new treatment approaches to overcome them. In the present study, we analyzed the expression of chemokines and their ligands in systemic and testicular DLBCL. From our biopsy sample set of 21 testicular and 28 systemic lymphomas, we were able to demonstrate chemokine profile differences and identify associations with clinical risk factors. High cytoplasmic CXCL13 expression had correlations with better treatment response, lower disease-related mortality, and limited stage. This study suggests that active CXCR5/CXCL13 signaling could overtake the CXCR4/CXCL12 axis, resulting in a better prognosis.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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