ASCO 2024 highlights

Welcome to our coverage of the 2024 ASCO Annual Meeting (ASCO 2024), held in Chicago, USA, from 31 May to 4 June 2024. Read on for the latest advances in the treatment of diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma (cHL), and natural killer/T-cell lymphoma (NKTCL), as well as innovative therapies for relapsed/refractory (R/R) lymphomas.

DEB study backs tucidinostat plus R-CHOP in double expressor DLBCL

The randomised, double-blind, placebo-controlled, phase 3 DEB study has confirmed the benefit of tucidinostat added to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with DLBCL and double expression of MYC and BCL2 proteins (DE).

Weili Zhao (Shanghai Institute of Hematology, China) presented the results from 423 previously untreated patients with DLBCL and DE who were randomised in a 1:1 ratio to receive six cycles of R-CHOP plus either tucidinostat or placebo. Patients who achieved a complete response with the combination therapy continued with either tucidinostat or placebo as maintenance treatment for up to 24 weeks.

The 24-month event-free survival (EFS) rate was significantly higher in the tucidinostat group at 58.9% versus 46.2% in the placebo group

At the interim analysis cutoff, with a median follow-up time of 13.9 months, 152 event-free survival (EFS) events were observed. The tucidinostat group exhibited a significantly lower incidence of EFS events compared with the placebo group (30.3% vs 41.5%). The 24-month EFS rate was 58.9% in the tucidinostat group versus 46.2% in the placebo group, with an HR of 0.68 (P=0.018). Moreover, the complete response rate (CRR) was significantly higher in the tucidinostat group at 73.0% compared with 61.8% in the placebo group, highlighting an adjusted difference of 11.1% (P=0.014).

The safety profile was consistent with previous studies, with no new safety concerns identified. Haematological adverse events of grade 3 or higher were more frequent in the tucidinostat than placebo groups, with the most common being neutropenia (60.2 % vs 45.3%), leukopenia (58.3% vs 44.8%) and lymphopenia (33.6% vs 31.1%).

Professor Wojciech Jurczak (Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland) discusses pivotal findings from the ECHELON-3 study, presented at ASCO 2024. View transcript.

BrECADD versus BEACOPP in advanced-stage cHL

Peter Borchmann (University Hospital of Cologne, Germany) reported the final analysis of the phase 3 GHSG HD21 trial, which evaluated the tolerability and efficacy of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) versus BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in patients with advanced-stage cHL. The trial aimed to determine if the novel BrECADD regimen, guided by positron emission tomography after two cycles (PET2), could improve treatment outcomes compared with the intensified BEACOPP regimen.

The 4-year progression-free survival (PFS) was significantly better with BrECADD at 94.3% compared with 90.9% for BEACOPP

The trial included 1,482 patients who were randomised to receive either BEACOPP or BrECADD, guided by PET2 results. During a follow-up of 48 months, there was a significant reduction in acute and severe treatment-related events with BrECADD versus BEACOPP, at 42% versus 59% (RR, 0.72; P<0.0001), which Borchmann stressed was a clinically meaningful difference.

The 4-year progression-free survival (PFS) was 94.3% for BrECADD compared with 90.9% for BEACOPP, with an HR of 0.66 (P=0.035). The PFS benefit of BrECADD was primarily due to a reduction in early treatment failures and was observed across all investigated subgroups.

CLAMP regimen shows efficacy in NK/T-cell lymphoma

Immune checkpoint blockers have shown promising results in patients with NKTCL, and the phase 2 CLAMP study aimed to evaluate the novel combination of camrelizumab with pegaspargase, etoposide, and high-dose methotrexate (CLAMP) in this population.

The single-arm study enrolled 41 patients with NKTCL. Nineteen had early-stage (Ann Arbor I/II) disease and received involved-field radiotherapy plus three to four cycles of the CLAMP regimen, whereas the 22 with advanced-stage or relapsed/refractory disease (Ann Arbor III/IV) received radiotherapy plus six cycles of CLAMP.

Tao Liu (Cancer Centre, Union Hospital, Wuhan, China) reported a high overall response rate (ORR) of 95.1%, with a CRR of 87.80%

The ORR was 100% in the early-stage group and 90.91% in the advanced-stage group. The 2-year PFS rate was 72.8%, and the overall survival (OS) rate was 88.0%. Haematologic toxicity was common but manageable, with the most frequent events of at least grade 3 being neutropenia (73.2%), thrombocytopenia (36.6%), and hypoalbuminuria and hypofibrinogenemia (both 24.4%). There were no treatment-related deaths.

Brentuximab vedotin with lenalidomide and rituximab in R/R DLBCL

Jeong-A Kim (St. Vincent’s Hospital, The Catholic University of Korea, Suwon, South Korea) presented an interim analysis of the double-blind global phase 3 ECHELON-3 study, which investigated the combination of brentuximab vedotin (BV) with lenalidomide and rituximab (R2) in patients with relapsed/refractory DLBCL.

In ECHELON-3, patients with relapsed/refractory (R/R) DLBCL ineligible for haematopoietic stem cell transplant or CAR T-cell therapy were randomised 1:1 to receive BV+R2 or placebo+R2. The interim analysis was conducted at 134 OS events, at which point the primary endpoint of OS was a median of 13.8 months for BV+R2 versus 8.5 months for R2 (HR, 0.629; P=0.0085). For secondary endpoints, the median PFS was 4.2 months for BV+R2 versus 2.6 months for R2 (HR, 0.527; P<0.0001), ORR was 64.3% versus 41.5% (P=0.0006), and the CRR was 40.2% versus 18.6%.

The median OS was significantly longer for BV+R2 at 13.8 months compared with 8.5 months for R2

The safety profile was manageable, although the rate of grade ≥3 treatment-emergent adverse events was higher in the BV+R2 group (88% vs 77% in the placebo group).

“The old and traditional standard of care is standard of the past." Professor Wojciech Jurczak (Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland) describes the key themes to emerge from ASCO 2024 and EHA2024, and highlights a surprising role for vitamin C supplementation in the treatment of myeloid malignancies. View transcript.

Glofitamab monotherapy in heavily pretreated R/R MCL

Tycel Phillips (City of Hope National Medical Centre, Duarte, California, USA) presented updated results from a phase 1/2 study on glofitamab monotherapy in patients with heavily pretreated R/R mantle cell lymphoma (MCL). Glofitamab, a bispecific antibody with a novel 2:1 (CD20) format, engages and redirects T cells to eliminate malignant B cells.

In this study, patients (N=61) received obinutuzumab pretreatment followed by glofitamab step-up dosing. At the median follow-up of 17.2 months, the ORR was 85.0%, with a CRR of 78.3%. Median duration of complete response was 15.4 months, and the median PFS was 16.8 months. The safety profile was manageable, with cytokine release syndrome being the most common adverse event. Events of grade 3 or above occurred in 80% of the cohort.

These positive data have led to the US Food and Drug administration (FDA) granting breakthrough therapy designation status to glofitamab for the treatment of patients with R/R MCL after at least two systemic therapies