Early PET scans guide de-escalation of therapy for advanced Hodgkin’s lymphoma
ORLANDO, Fla. — PET scans performed following two cycles of the chemotherapeutic regimen BEACOPP can be safely used to guide subsequent treatment, according to results of an interim analysis of a phase 3 trial presented at the ASH Annual Meeting and Exposition.
These results support the delivery of ABVD chemotherapy — which includes doxorubicin, bleomycin, vinblastine and dacarbazine — without hindering disease control for patients with advanced-stage Hodgkin’s lymphoma who have a negative PET after two treatment cycles. However, PET positivity after two cycles of BEACOPP — which includes bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine (Matulane, Sigma Tau) and prednisone — appeared associated with a higher risk for disease progression.
“This approach allows to significantly reduce treatment-related immediate toxicity in most patients and provides a similar outcome compared with standard BEACOPP treatment,” Olivier Casasnovas, MD, of CHU Dijon Bourgogne in Dijon, France, said at the presentation.
Although escalated BEACOPP chemotherapy has demonstrated better disease control than the ABVD regimen, escalated BEACOPP also leads to higher immediate hematological toxicity and increased risks for a secondary myelodysplasia, leukemia and infertility.
Casasnovas and colleagues sought to determine if PET performed after two cycles of BEACOPP chemotherapy would identify patients who could step down to ABVD. They implemented this strategy into the AHL 2011 trial, which included patients with Hodgkin’s lymphoma aged 16 to 60 years.
The analysis included 823 patients with high-risk stage IIB or Ann Arbor stage III to stage IV Hodgkin’s lymphoma enrolled between May 2011 and May 2014, of whom 782 were eligible for the interim analysis.
The experimental arm of the study included 401 patients who underwent PET imaging after two cycles of BEACOPP. If PET positive, patients continued and received four additional cycles of escalated BEACOPP. If PET negative, patients instead received four cycles of ABVD.
The control arm included 381 patients who received the standard regimen of six cycles of BEACOPP regardless of PET status.
The primary endpoint was PFS.
After two cycles of BEACOPP, 12% of patients on the control arm and 13% on the experimental arm were PET positive.
Based on these results, 84% of the patients in the experimental arm received four cycles of ABVD and 13% continued with BEACOPP for four additional cycles.
Toxicities of grade 3 or worse appeared significantly higher among patients who remained on the BEACOPP regimen compared with those who de-escalated to ABVD. The patients remaining on BEACOPP had more frequent anemia (11% vs. 2%), leukopenia (85% vs. 72%), thrombocytopenia (44% vs. 13%) febrile neutropenia (6% vs. 3%) and sepsis (7% vs. 4%) than those who switched to ABVD.
Overall 24% of the patients who remained on BEACOPP experienced serious adverse events related to their treatment, including four deaths. Comparatively, 15% of patients who switched to ABVD experienced a serious adverse event, including one death (P < .002).
The researchers noted that 67% of those patients who experienced serious adverse events in the experimental arm had them occur prior to de-escalation.
The estimated rate of 2-year PFS was similar in both arms (91.6% in the control arm, 88.3% in the experimental arm) after a median follow-up of 16.3 months.
Significantly fewer patients who had positive PET achieved 2-year PFS in the entire cohort (72.9% vs. 92.8%; P < .0001). These results appeared comparable in the standard arm (75.1% vs. 94%) and the PET-driven experimental arm (70.8% vs. 91.6%; P ˂ .0001 for both). – by Anthony SanFilippo
Casasnovas O, et al. Abstract 577. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.
Disclosure: The researchers report consultant/advisory and speakers bureau roles with and research funding from AbbVie, Calistoga Pharmaceuticals, Celgene, Genentech, Gilead, Janssen, Roche and Takeda.