HL

ASCO® 2016: Brentuximab Vedotin Consolidation After ABVD Treatment Increases Rates of PET-Negative Disease in Patients with Non-Bulky Hodgkin Lymphoma

This ASCO 2016 oral abstract presentation took place on Sunday June 5, 9:45am–12:45pm, during the ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ session. This session was chaired by Pr Gilles Salles, Head of the Hematology Department in South Lyon hospitals, Lyon, France.

The abstract (#7508was presented by Dr Steven I Park, Director of the Lymphoma Program and Associate Professor of medicine at UNC,  at Chapel Hill Lineberger Comprehensive Cancer Center in Chapel Hill, NC.

Chemotherapy with or without radiotherapy is currently the standard care option for patients with limited stage Hodgkin lymphoma (HL). There is a paucity in the knowledge of the long-term side effects that result with consolidative radiation therapy, as well as if it confers a clear OS advantage, and so its use in HL is an area of controversy. An active agent that has emerged is brentuximab vedotin (BV). The group who authored this abstract aimed to assess whether BV can effictively and safely eradicate residual disease after induction chemotherapy; potentially replacing radiation as consolidation in patients with limited stage HL.

Beginning in April 2012, the LCCC 1115 multicentric, phase II study (NCT01578967) aimed to investigate induction chemotherapy plus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) followed by BV consolidation as therapy for untreated, non-bulky, stage I or II HL.

Overall, 41 patients with a median age of 29 years (range, 19–67) were enrolled on the trial, and the primary outcome measure was feasibility, defined as the percentage of patients that convert to PET-negative disease post-brentuximab consolidation. Secondary outcome measures included progression free survival and toxicity. Inclusion criteria consisted of an age range of 18–60 years, ECOG performance status of 0–2, and a life expectancy of ≥3 months.

ABVD was administered in 2–6 cycles to patients based on their baseline risk factors and interim PET scan result. This was followed around 6 weeks later with 1.8mg/kg BV as consolidation given every 3 weeks for up to 6 cycles. 

BV resulted in promising clinical activity and demonstrated an acceptable safety profile. PET-negative disease was achieved in 72% of patients after 2 cycles of ABVD, rising to 90% of patients after BV consolidation. The authors indicate that BV consolidation may eradicate the need for radiation therapy.

  • 46% of pts presented with unfavorable disease (B symptoms, ESR >50, or >3 sites of disease
  • ≤4 cycles of ABVD administered to over 90% of pts; 1 patient received radiation due to PD
  • Grade ≥ 3 toxicities associated with BV included neutropenia (n=3), peripheral neuropathy (n=1), and rash (n=1)
  • One death reported due to sepsis and hepatic failure; all reported ≥Grade 4 toxicities were associated with this event
  • After 2 cycles of ABVD, PET-negative disease = 72% of pts; after completion of BV, PET-negative disease = 90% of pts
  • Median follow-up = 17 months; estimated one-year PFS = 91% (95% CI, 75–97%); estimated one-year OS = 97% (95% CI, 81–100%)

It was concluded that BV following ABVD demonstrates promising activity and resulted in PET-negativity in around 95% of patients. All patients who achieved negativity by PET after BV remain in remission. Only 2 cycles of ABVD were administered to 27.5% (11/40) patients and all remain in remission, providing strong evidence that the dosage of conventional chemotherapy can be reduced. Furthermore, PET positive patients at the end of therapy (5%) were successfully treated with ASCT with or without radiotherapy. The one death reported resulted from a very rare, but know, complication of BV. Lastly, a limitation of this study was its relatively short follow-up. Longer follow-up is required, with a 5-year PFS being planned.

Reference

1. Park SI, et al. A phase 2 trial of ABVD followed by brentuximab vedotin consolidation in limited stage non-bulky Hodgkin Lymphoma. J Clin Oncol 34, 2016 (suppl; abstr 7508).