Hodgkin Lymphoma in a Summary of News from Post-ASH 2021
Dr. Anna Suredová from the Clinical Hematology Department of the Catalonian Oncology Institute in Barcelona, newly elected president of the European Society for Bone Marrow Transplantation (EBMT), also remotely participated in this year's Prague Hematology Days (PHD 2022). In her lecture, she presented an overview of highlights from 4 clinical studies regarding Hodgkin lymphoma (HL) presented during the Post-ASH 2021 meeting.
New Independent Prognostic Factors in aHL
In the multicenter phase III study AHL2011, PET-guided therapy for aHL proved to be effective. The examination after 2 cycles of induction therapy (PET2) with the intensified BEACOPP (BEACOPPesc) regimen allowed for de-escalation to the ABVD regimen in individuals with negative scans, reducing treatment toxicity without lowering its effectiveness compared to 6 cycles of BEACOPPesc. By analyzing baseline PET/CT scans, additional prognostic factors were identified, including total metabolic tumor volume (TMTV) and SDmax (maximum distance between defined lesions normalized by body surface area). TMTV quantifies tumor burden, and SDmax assesses tumor dissemination.
Kanoun et al. from the University Cancer Center in Toulouse, France, evaluated these new prognostic factors extracted from the baseline PET/CT in a subset of 634 newly diagnosed advanced HL (aHL) stage III–IV patients according to the Ann Arbor classification, who participated in the AHL2011 study. The median follow-up time was 5.6 years. The prognostic significance was analyzed using the 5-year progression-free survival (PFS) parameter.
Patients with low values in both parameters had a higher 5-year progression-free survival compared to patients with high TMTV and/or SDmax (92.0 vs. 83.4%; hazard ratio [HR] 2.24; 95% confidence interval [CI] 1.39–3.62; p = 0.0007). Both parameters outperformed the International Prognostic Score (IPS) and should be integrated into personalized treatment strategies for aHL patients in terms of prognostic value.
Brentuximab Vedotin + CHT and Prognostic Factors in R/R HL Patients
Driessen et al. from the University Medical Center in Amsterdam conducted a large analysis of individual patient data from 9 studies, evaluating the addition of brentuximab vedotin (BV) to chemotherapy (CHT) and prognostic factors in relapsed or refractory HL (R/R HL) patients.
Dr. Suredová noted that approximately 60% of R/R classical HL (R/R cHL) patients achieve long-term PFS after salvage CHT and autologous stem cell transplantation (ASCT). Combination BV + CHT was evaluated in several phase II studies, but no randomized controlled studies were conducted. The authors of this pooled analysis assessed the effect of adding BV to salvage CHT (7 studies, n = 391) compared to CHT alone (2 studies, n = 327) on PFS, OS, and pre-ASCT PET response.
It appears that adding BV to CHT followed by ASCT prolongs PFS in relapsed, but not primarily refractory cHL. OS improved in the BV cohort but could be influenced by advancements in post-ASCT treatment over time. During CHT-alone study periods, BV and checkpoint inhibitors were not available. This analysis also confirmed the strong prognostic value of complete metabolic response (mCR) before ASCT for PFS. B symptoms, stage, and primarily refractory disease were prognostic for PFS and mCR achievement before ASCT.
The Role of BV in R/R cHL Patients
R/R cHL patients remain a therapeutic challenge. The standard of care is consolidation with ASCT. Achieving complete metabolic remission with salvage CHT improves long-term outcomes post-ASCT. The introduction of new drugs brought progress. The GELTAMO group demonstrated that BV + ESHAP regimen could achieve mCR in 70% of R/R HL patients before ASCT. However, the superiority of BV + CHT compared to CHT alone was not tested in prospective randomized clinical trials. Additionally, it is unknown if BV consolidation could spare a subset of R/R HL patients with low risk from undergoing ASCT. Preliminary data from the Spanish phase IIb BRESELIBET study (n = 150) addressing this question were presented during Post-ASH 2021. Dr. Suredová is also a member of the research team.
BRESELIBET is a randomized study aiming to verify the efficacy and safety of 3 cycles of salvage therapy BV-ESHAP compared to ESHAP in R/R HL and to evaluate the efficacy and safety of BV consolidation in patients who achieved mCR after salvage therapy. Interim results presented with low patient numbers do not yet confirm BV-ESHAP superiority, but it is evident that BV consolidation may be beneficial. Safety data so far show no surprises, only expected adverse events. The study will continue until patient recruitment is completed.
Incorporating targeted therapy (BV, checkpoint inhibitors) can, according to the speaker, improve outcomes for both first- and second-line HL treatments. The question remains whether ASCT could be replaced with targeted therapy in some patient subsets.
Pembrolizumab + AVD in Previously Untreated cHL
Dr. Suredová also mentioned the work of American researchers from Washington University and Fred Hutchinson Cancer Research Center in Seattle. She prefaced that in North America, the standard first-line treatment for cHL is the ABVD regimen. PD-1 receptor inhibitors show significant activity in R/R cHL but are not curative for most patients. It might be ideal to incorporate them into the first line of treatment, utilizing the patient’s relatively intact immunity. Lynch et al. tested the hypothesis that concurrent pembrolizumab with AVD (APVD) is a safe and effective therapy for newly diagnosed cHL.
From February 1, 2019, to June 18, 2021, a total of 36 patients were evaluated, 30 were treated, and 29 completed at least 2 cycles of therapy. Pembrolizumab + AVD without initial PD-1 blockade was safe and effective. PET2 results showed 100% response, with 66% achieving complete remission. One-year progression-free survival (PFS) was 96%. Elevated liver transaminases were more frequent than with ABVD but reversible. Interrupting pembrolizumab due to this did not affect therapy efficacy. FDG-PET utility in PD-1 inhibitor-containing combinations was not supported; PET2 positivity was not linked to a high relapse risk, and only 20% of patients with positive end-of-treatment PET scans developed recurrent cHL.
APVD was effective and well-tolerated, as stated by the speaker, and can be further evaluated for all cHL stages.
Eva Srbová
MeDitorial editorial team
Source: Sureda A. Hodgkin lymphoma. 22nd Prague Hematology Days – Hematology 2022 – Post-ASH, January 20, 2022.
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