Welcome to our coverage of the 2024 European Hematology Association Annual Congress (EHA2024), held in Madrid, Spain, on 13–16 June 2024. Read on for the latest advances in the treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL), including innovative biomarker-adapted strategies and new therapies for high-risk and relapsed/refractory lymphomas.
ECHO expands options for older adults with MCL
Frontline treatment with acalabrutinib combined with bendamustine and rituximab led to a 27% reduction in the risk of disease progression or death in older patients (≥65 years) with MCL, according to findings from the phase 3 ECHO trial presented at EHA2024. The independent review committee-assessed median progression-free survival (PFS) for participants taking acalabrutinib + bendamustine was 66.4 months compared with 49.6 months with placebo + bendamustine, showing a statistically significant improvement. When censored for COVID-19 deaths, the risk reduction was 36%.
A total of 19.1% and 33.1% of patients in the acalabrutinib + bendamustine (n=299) and placebo + bendamustine arms (n=299), respectively, had progressive disease. Of those patients on bendamustine alone, 69% received a Bruton’s tyrosine kinase (BTK) inhibitor as a subsequent treatment, noted lead study author Michael Wang (The University of Texas MD Anderson Cancer Center, Houston, USA).
The safety profile of acalabrutinib + bendamustine was consistent with that of the individual drugs.
The survival trend favouring acalabrutinib + bendamustine was sustained despite most patients receiving a BTK inhibitor as salvage therapy after disease progression with bendamustine
Professor Wojciech Jurczak Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland) highlights the key messages on safety and dosing schedules to emerge from the ECHELON-3 study. View transcript.
Updated STARGLO data reveal survival benefit for DLBCL
Adding fixed-duration glofitamab-gxbm to gemcitabine and oxaliplatin significantly improved overall survival (OS) and PFS in patients with relapsed/refractory DLBCL who were not eligible for autologous stem cell transplant, according to updated findings from the phase 3 STARGLO study.
At a median follow-up of 20.7 months, the median OS with glofitamab was 25.5 months, compared with 12.9 months with rituximab + gemcitabine/oxaliplatin, translating to a significant 38% reduction in the risk of death. Additionally, the median PFS was 13.8 months with glofitamab versus 3.6 months with rituximab, indicating a 60% reduction in the risk of disease progression or death.
Jeremy Abramson (Massachusetts General Hospital Cancer Center, Boston, USA) highlighted that glofitamab is the first CD20 × CD3 bispecific antibody to show a survival benefit in DLBCL in a randomised phase 3 trial.
The study included 274 patients randomised 2:1 to receive either the glofitamab regimen or rituximab, with those in the experimental arm receiving pre-treatment with obinutuzumab. The safety profile of glofitamab was consistent with the known risks of the individual study drugs, with most adverse events (AEs) being manageable. Any-grade AEs occurred in all patients who received the glofitamab regimen compared with 95.5% of those given the rituximab regimen; 82.8% versus 65.9% of these effects were related to glofitamab or rituximab, respectively. Serious AEs occurred in 54.4% of patients on glofitamab versus 17.0% on rituximab, with 34.4% versus 8.0% related to the respective treatments. Grade 3–5 AEs were observed in 77.8% of those in the glofitamab arm versus 40.9% in the rituximab arm, with significant occurrences including neutropenia (33.9%), infections (23.3%), and cytokine release syndrome (2.3%). Fatal AEs occurred in 8.3% of patients receiving glofitamab versus 4.5% receiving rituximab, with 2.8% versus 1.1% associated with the respective treatments. Additionally, 26.7% of patients on the glofitamab regimen discontinued treatment due to toxicity, compared with 12.5% on the rituximab regimen.
These results support the use of glofitamab plus gemcitabine and oxaliplatin for the treatment of relapsed/refractory DLBCL.
Jeremy Abramson
Professor Wojciech Jurczak discusses the most important takeaways from EHA2024, with a focus on the STARGLO findings and data on mosunetuzumab in follicular lymphoma. View transcript.
Biomarker-adapted treatment in high-risk LBCL
The Nordic phase 2 LBC-06 trial (presented by Sirpa Leppä, University of Helsinki and Helsinki University Hospital, Finland) evaluated a biological risk-adapted treatment strategy in patients <65 years with high-risk LBCL. At a median follow-up of 52 months, the study reported a 5-year failure-free survival (FFS) of 75% and an OS of 89%. The trial included 123 patients, with 61 (50%) stratified into a biologically high-risk group due to factors including C-MYC translocation, 17p/TP53 deletion, and immunohistochemical co-expression of MYC and BCL2.
Intensified immunochemotherapy demonstrated a favourable outcome in patients with high-risk LBCL, particularly benefiting those with an age-adjusted International Prognostic Index of three (aaIPI3) and biological risk factors
Treatment involved two cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and high-dose methotrexate, followed by DA-EPOCH-R (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, rituximab) for the high-risk group, based on biological risk factors. Other patients received R-CHOEP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone every 2 weeks) and one course of rituximab and high-dose cytarabine.
Notably, the DA-EPOCH-R regimen showed improved survival in patients with aaIPI3, with a 5-year OS of 93% compared with 62% receiving R-CHOEP-14 (P=0.044). However, high pretreatment circulating tumour DNA (ctDNA) levels, being ctDNA positive after two treatment cycles or at the end of therapy, and having a 17p/TP53 deletion or TP53 mutations were linked to inferior OS.
“It may change the standard of care in mantle cell lymphoma.” Professor Wojciech Jurczak highlights the most important data on the use of molecularly targeted therapies presented at ASCO 2024 and EHA2024. View transcript.
Atezolizumab consolidation in high-risk DLBCL
Marcel Nijland (University Medical Center Groningen, the Netherlands) presented the results of the HOVON 151 study, which evaluated the feasibility and clinical efficacy of atezolizumab consolidation therapy in patients with high-risk DLBCL who achieved complete metabolic remission after R-CHOP.
The phase 2, single-arm, open-label study enrolled 109 patients, who received atezolizumab for up to 18 cycles. At a median follow-up of 36.4 months, the 2-year disease-free survival (DFS) rate was 87.9% while the 2-year OS rate was 96.3%.
Any-grade AEs associated with treatment were prevalent, with infections occurring in 75.1% of patients, half of which were COVID-19 related. Other notable AEs included investigations (20.6%), musculoskeletal tissue disorders (2.7%), and nervous system disorders (1.6%). Grade 3–4 AEs were observed in endocrine (2.8%), colitis (0.9%) and neurological (0.9%) categories. Grade 3–4 immune-related adverse events were reported in 4.5% of cases.
These results suggest that atezolizumab consolidation therapy can enhance DFS and OS in patients with high-risk DLBCL, providing a new therapeutic option to reduce measurable residual disease post R-CHOP
