ICML 2017: Response-adapted therapy for Hodgkin’s lymphoma

Professor Peter Johnson (Southampton, UK) tells us what’s new with response-adapted therapy and what are the benefits to patients.

Mortality in Hodgkin’s lymphoma (HL) has fallen steadily over the last 30 years and HL can now be regarded as highly curable. However, there is still scope for improving outcomes in some patients, including those with high-risk disease at baseline, and patients with positive interim PET scans. In his Meet the Professor session at ICML 2017, Professor Peter Johnson from Southampton outlined how response-adapted therapy can help to improve long-term outcomes and optimise the use of new agents in HL.

It is estimated that on average 80% of patients with HL are cured with first-line therapy, and more than 80% of patients are still alive after 10 years. Ongoing research in this field is primarily focusing on improving these outcomes further, and also to minimise toxicity – patients who are treated for HL as young adults are at risk of developing treatment-related adverse effects later in life, such as myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) from alkylating agents, solid tumours from radiation, pulmonary fibrosis from bleomycin, ischaemic heart disease from mediastinal radiation and doxorubicin, and infertility from alkylating agents. Although modern therapies are associated with reduced toxicity, there remains the dilemma of balancing the probability of cure against the risk of morbidity in each individual patient.

The 5-point Deauville score for fludeoxyglucose (FDG)-PET has been shown to be a highly reproducible tool for determining HL activity.^{1, 2} An interim PET scan performed after the initial treatment cycles can be used to guide subsequent treatment and allow therapy to be escalated or de-escalated to improve efficacy and minimise toxicity. The RAPID study showed that patients with early-stage HL who were PET-negative after three cycles of ABVD had very good progression-free survival (PFS) and overall survival (OS) either with or without consolidation radiotherapy.³ In the recent H10 study patients with early-stage HL who were PET-positive after two cycles of ABVD achieved significantly improved PFS rates when switched to escalated BEACOPP with radiotherapy; PFS and OS rates were very high in patients who were interim PET-negative irrespective of consolidation radiotherapy, although patients with favourable disease (Stage I or II with no risk factors at baseline) achieved slightly higher PFS rates with radiotherapy than without.⁴ In advanced HL, the RATHL and LYSA studies show that it is possible to de-escalate therapy by omitting bleomycin in interim PET-negative patients without any loss of disease control or OS.^{5, 6} Professor Johnson emphasised that iPET scans with subsequent escalation or de-escalation of therapy offer a means of personalising the treatment strategy. In addition, it also allows for rapid testing of new approaches eg in patients with high-risk disease or who fail to respond to existing treatments.

Professor Johnson also discusses the prognostic value of PET after immunotherapy.

Interim PET scans are less reliable in patients with more advanced disease, and there is therefore a need for strategies to improve the negative predictive value of interim PET scans. Dr Lucy Pike from King’s College London presented results from the RATHL study which indicate that a PET-CT scan performed at baseline can help to predict the disease prognosis and the interim PET result. In this prospective analysis, 100 patients underwent PET-CT at baseline and the metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured overall and for the bulkiest lesion, and the number of extranodal sites counted. The results showed that patients who were interim PET-positive had significantly higher total and bulk MTV and TLG at baseline compared with those who were interim PET-negative (p<0.0002). TLG was significantly associated with PFS and HL events in univariate and multivariate analysis. The investigators suggested that TLG should be included in risk assessment models in advanced HL for improved prognostic value.

References

1. Meignan M, Gallamini A, Meignan M, et al. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma 2009;50:1257-60.
2. Barrington SF, Qian W, Somer EJ, et al. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging 2010;37:1824-33.
3. Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med 2015;372:1598-607.
4. Andre MPE, Girinsky T, Federico M, et al. Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol 2017;35:1786-1794.
5. Johnson P, Federico M, Kirkwood A, et al. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma. N Engl J Med 2016;374:2419-29.
6. Casasnovas O, Brice P, Bouabdallah R, et al. Randomized Phase III Study Comparing an Early PET Driven Treatment De-Escalation to a Not PET-Monitored Strategy in Patients with Advanced Stages Hodgkin Lymphoma: Interim Analysis of the AHL2011 Lysa Study. Blood 2015;126:577-577.