Examining a PET-Response–Adapted Strategy in Patients with Advanced Hodgkin Lymphoma

Positron emission tomography (PET) performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma (HL) can identify patients who would benefit from therapy escalation, according to a report recently published in the Journal of Clinical Oncology.

In the phase II HD0801 study, Pier Luigi Zinzani, MD, from the Sant’Orsola-Malpighi University Hospital in Italy, and colleagues examined whether poor response to ABVD chemotherapy (determined by PET-positivity) could provide a rationale to shift patients to a more intensive treatment regimen.

“This strategy is opposed to the conventional approach of addressing patients to salvage treatment only after a disease relapse or resistance is demonstrated,” Dr. Zinzani told ASH Clinical News.

The multicenter study assessed two-year progression-free survival (PFS; the primary endpoint) and overall survival (OS; the secondary endpoint) among 519 patients with advanced-stage de novo HL who received initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

If patients had a PET-positive evaluation after two cycles of chemotherapy (PET2-positive), they underwent an ifosfamide-containing salvage treatment followed by hematopoietic cell transplantation (HCT). If patients were PET-negative, they received four or more additional cycles of ABVD.

Within the study population, 103 evaluable patients (20%) were PET2-positive, meaning treatment was at high risk for failing. Of those patients:

  • 81 received the scheduled salvage regimen with HCT
  • 15 remained on ABVD therapy
  • 5 received an alternative treatment
  • 2 were excluded from the study due to diagnostic error

Twenty-one patients in the PET2-positive group and 73 in the PET2-negative group experienced disease progression. Eight patients in the PET2-positive group and nine patients in the PET2-negative group died during the study follow-up period.

Among the 81 patients who received salvage treatment, grade 3 and 4 adverse events were primarily hematologic and treatment-related, including neutropenia (11% and 60%) and thrombocytopenia (15% and 49%). No treatment toxicity-related hospitalizations or deaths occurred, “thus achieving a favorable toxicity profile for such an intensive therapeutic strategy,” the authors wrote.

In an intention-to-treat analysis, rates of two-year PFS after a median follow-up of 25 months from PET scanning were similar between PET2-negative and PET2-positive patients (regardless of the salvage treatment they received): 81 percent (95% CI 76-84) and 76 percent (95% CI 66-84), respectively. “[These patients] appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70 percent of PET2-positive patients through obtaining the same two-year PFS as the PET2-negative subgroup,” the authors concluded.

“Our data support the efficacy and feasibility of early treatment intensification in a small proportion of patients with Hodgkin lymphoma considered at high risk for failure, as identified by an interim PET2 positivity,” Dr. Zinzani told ASH Clinical News.

The authors noted one result limiting the study’s findings: A group of 15 PET2-positive patients received four or more cycles of ABVD as a result of the physician’s or patient’s refusal to switch to the treatment program, and 73 percent achieved a complete response, “indicating the existence of a proportion of patients who can obtain a complete response even though they show PET positivity at early evaluation.”

Given this finding, there is a risk of over-treatment of PET2-positive patients, and longer follow-up is necessary to confirm the validity of this PET response-adapted strategy in advanced HL patients.


Reference

Zinzani PL, Broccoli A, Gioia DM, et al. Interim positron emission tomography response—adapted therapy in advanced-stage Hodgkin lymphoma: Final results of the phase II part of the HD0801 study. J Clin Oncol. 2016 Feb 16. [Epub ahead of print]

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