ORLANDO, FL—After 2 cycles of escalated BEACOPP (BEACOPPesc) chemotherapy for advanced stage Hodgkin lymphoma, PET “can be safely used to guide subsequent treatment,” interim analysis of a study conducted by the Centre Hospitalier Universitaire (CHU) Dijon, Dijon in has found.1
The study, presented at the 57th American Society of Hematology (ASH) Annual Meeting, sought to determine whether PET, performed after 2 cycles of upfront BEACOPPesc, might identify a population suitable for receiving subsequent doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy; that is, those “able to benefit from a strategy of dose intensity de-escalation” without impairing disease control, said Olivier Casasnovas, MD, of Hopital Le Bocage, CHU Dijon.
To date, studies have shown that escalated BEACOPP—bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone—demonstrates better disease control than ABVD, but does not improve overall survival. In this study, after 2 BEACOPPesc cycles and PET, patients were randomly assigned to receive 4 cycles of ABVD if PET-negative and 4 cycles of BEACOPPesc if PET-positive. In the control arm, patients received a standard treatment not monitored by PET, 6 cycles of BEACOPPesc.
Of the 823 patients in the study, 782 were eligible for the interim analysis, 401 in the PET-driven arm and 381 in the control arm. Median age was 30 years (range, 16-60); 64% were male; 73% had nodular sclerosis, 6% had mixed cellularity Hodgkin lymphoma, and 17% had other types or unclassified Hodgkin lymphoma. A total of 11% of patients had stage 2B disease; 28%, stage 3; 60%,stage 4; and 58% had an international prognosis score of 3 or higher.
After 2 cycles of BEACOPPesc, PET was positive in 48 (12%) of patients in the standard arm and 49 (13%) in the experimental arm, Dr Casanovas said. Based on these results, 319 patients (84%) in the experimental arm received 4 cycles of ABVD and 49 (13%), 4 additional cycles of BEACOPPesc.
A median follow up of 16.3 months (range, 0.1-37.4 months), estimated 2-year progression-free survival was similar in the standard (91.6%) and PET-driven arms (88.3%; P = .79), he reported.
However, PET positivity was related to a significantly lower 2-year progression-free survival compared to PET-negative patients, 72.9% vs 92.8%; P < .0001. When examined by PET-driven strategy, 2-year progression-free survival was 95% in patients who were PET-negative after 2 cycles, 78% among those who were PET-positive, and 42% in the standard arm.
“Grade 3 or higher toxicity was significantly higher in patients receiving 6 cycles of BEACOPPesc compared to those who received 2 cycles of BEACOPPesc plus 4 cycles of ABVD, with more frequent anemia (11% vs 2%; P < .000001), leukopenia (85% vs 72%; P = .00003), thrombocytopenia (44% vs 13%; P < .000001), febrile neutropenia (6% vs 3%; P < 0.04), and sepsis (6.5% vs 3.9%; not significant),” Dr Casanovas said.
In the control arm, 182 serious adverse events related to treatment occurred in 108 patients (24%), which led to 4 deaths, compared to 72 serious adverse events, including 1 death, in 50 patients (15%) treated with BEACOPPesc and ABVD (P < .002). Most of these events, 67%, occurred during the first 2 cycles of chemotherapy.
“PET positivity after 2 cycles of BEACOPPesc is related to a higher risk of disease progression,” Dr Casanovas said, adding the “PET performed after 4 cycles of chemotherapy identifies a subset of paitents with a particularly poor outcome.”
These results should encourage development of new treatment options in patients with PET-positive advanced stage Hodgkin lymphoma, he concluded.
1. Casasnovas O, Brice P, Bouabdallah E, 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. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 7, 2016, Orlando, FL.