ASH 2024 highlights
ASH 2024 highlights
The American Society of Hematology (ASH) Annual Meeting and Exposition 2024 took place in San Diego, California, USA, on 7–10 December. Among the lymphoma hot topics discussed were efforts to reduce treatment toxicity and the first phase 3 trial combining two monoclonal antibodies for the treatment of follicular lymphoma (FL).
Removing TBI from allogeneic-HSCT conditioning regimens in PTCL
Data from a retrospective study in China indicated that patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) for peripheral T-cell lymphoma (PTCL) may forgo total body irradiation (TBI) during conditioning and still achieve excellent outcomes.
Hongye Gao (Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin) reported that the 2-year overall survival (OS) rate was 84.3% among 28 patients who received a non-TBI conditioning regimen, most commonly a busulfan-based protocol. By comparison, the rate was 49.4% among 22 patients given TBI-based conditioning, with no statistically significant difference between the two groups, even after propensity-score matching.
The findings were similar for high-risk subgroups, including patients with more than two lines of previous treatment and those not in remission prior to allo-HSCT.
“Our results have important implications for the selection of conditioning regimens in PTCL, as we suggest that non-TBI approaches may be considered a suitable alternative to TBI-based regimens, even in high-risk PTCL patients,” said Gao.
“We really need to have a prospective trial.” Francine Foss (Yale School of Medicine, New Haven, Connecticut, USA) discusses whether these retrospective findings are sufficient to support removing TBI from allogeneic HSCT conditioning regimens in PTCL. View transcript.
R-CHOP-like therapy for late-relapse DLBCL
The findings may allow patients with late-relapse DLBCL to avoid the toxicity of more intensive options
Jean-Nicolas Champagne (BC Cancer Vancouver, British Columbia, Canada) presented outcomes for 65 patients with diffuse large B-cell lymphoma (DLBCL) that had relapsed a median 7.4 years after their initial diagnosis. At relapse, the patients were treated with frontline curative intent with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CEOP (cyclophosphamide, etoposide ,prednisolone, rituximab, and vincristine).
After a median five cycles of treatment, the overall response rate was 72%, with 57% of patients achieving a complete response (CR). The median time to progression from late relapse was 45 months overall, but was just 6.6 months among the 14 patients who had relapsed between 2 and 5 years after their initial diagnosis compared with 86 months among the 51 patients who had relapsed after more than 5 years.
Champagne also reported that the cell of origin at late relapse was highly concordant (94%) with that from the original diagnostic biopsy, which suggests that late-relapse DLBCL may represent a new lymphoma arising from a common precursor cell that is essentially chemotherapy-naive.
Foss discusses whether R-CHOP is suitable for late-relapse DLBCL and if these patients can be classed as chemotherapy-naive. View transcript.
UK RAPID: PET to determine consolidation radiotherapy in cHL
Primary data from the UK RAPID trial, which was set up in 2003, indicated that patients with newly diagnosed stage 1A or 2A classical Hodgkin lymphoma (cHL) and a negative positron emission tomography (PET) scan after three cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) had similar 3-year survival outcomes regardless of whether they then received consolidation radiotherapy or no further treatment.
However, the follow-up period was too short to determine late consequences of treatment in a cohort that generally has extremely good outcomes. John Radford (University of Manchester, UK) and colleagues therefore used UK national datasets to determine the long-term outcomes of the 420 study participants.
He reported that after a median 16 years of follow-up, there was still no significant difference in OS between the two groups. The 15-year OS was 94.2% in PET-negative patients who received involved field radiotherapy (IFRT) and 92.3% in those who received no further treatment. The most common causes of death were respiratory causes, non-HL, cardiac causes, and cancer, with a similar distribution between the groups. There was only one death from HL, which occurred in the IFRT group.
Radford concluded: “IFRT only needs to be considered for those patients at high risk of recurrence.”
PET-guided bleomycin omission in limited-stage cHL
A policy change in the treatment of patients with limited stage cHL allowed Jiayu Yang (University of British Columbia, Vancouver, Canada) and colleagues to assess the impact of omitting bleomycin from treatment after two cycles of ABVD followed by negative PET results. Prior to 2016, these patients completed treatment with two further cycles of ABVD but after 2016 they were given two cycles of AVD instead.
Yang reported that 5-year OS among the 67 patients treated in the ABVD era was 98.4% and 100% among the 121 patients treated in the AVD era, a nonsignificant difference. There was also no difference in 5-year progression-free survival (PFS) rates, at 92.3% and 94.9%, respectively.
Most pulmonary toxicity occurred in the ABVD era, affecting 16% of patients. Nevertheless, four cases (8%) occurred in the AVD era, all during cycle 2.
Yang said the data show that excellent outcomes are preserved when bleomycin is omitted after two cycles of ABVD with a negative PET scan.
“I think these studies are going to be critically important moving forward.” Foss talks about the use of PET to guide treatment de-escalation in cHL. View transcript.
inMIND: Tafasitamab plus lenalidomide and rituximab R/R FL
This is the first study to validate combining two monoclonal antibodies – anti-CD19 with anti-CD20 – in the treatment of lymphoma
Presenting in the late-breaking abstracts session, Laurie Sehn (BC Cancer Centre for Lymphoid Cancer and The University of British Columbia, Vancouver, Canada) reported the primary data from the phase 3 inMIND trial, which evaluated efficacy and safety of adding the anti-CD19 monoclonal antibody tafasitamab to lenalidomide and rituximab in patients with relapsed refractory (R/R) FL or marginal zone lymphoma.
After a median 14 months of follow-up, the 273 patients given tafasitamab in addition to lenalidomide and rituximab had a significant 59% lower risk for disease progression, relapse, or death compared with the 275 patients given placebo. Independently assessed median PFS was not reached in the tafasitamab arm and was 16 months in the placebo arm. This benefit was consistent across high-risk subgroups.
The CR rate was 49.4% with tafasitamab versus 39.8% with placebo, the objective response rates were 83.5% and 72.4%, respectively, and the median durations of response were a corresponding 21.2 and 13.6 months.
Sehn said that the “safety profile was manageable and consistent with expected toxicities of these agents”.
She concluded: “Tafasitamab plus lenalidomide and rituximab can be administered in community as well as academic settings and represents a potential new standard of care option for patients with R/R FL.”
“What this study really demonstrated was a meaningful improvement in progression-free survival.” Foss discusses the inMIND trial in patients with R/R FL. View transcript.