Response-adapted frontline therapy for Hodgkin lymphoma: are we there yet?

Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [18F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%. Conversely, escalation to more intensive chemotherapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) for those with positive interim PET scans seems to be an effective strategy with improved disease control. In advanced-stage disease, several groups have elected to start treatment with ABVD and escalate to BEACOPP or myeloablative therapy for patients who remain PET positive after 2 cycles, which gives rates of disease control of ∼65%. De-escalation by omission of bleomycin and consolidation radiotherapy after a negative interim PET scan seems safe with no increase in recurrence rate, but the performance of interim PET after ABVD is suboptimal, especially for those with very advanced disease at presentation; recurrence rates after a negative scan are ∼15%. The negative predictive value of PET is higher after escalated BEACOPP chemotherapy, and the approach of initially treating with BEACOPP and de-escalating to ABVD for those with negative interim PET scans shows promising early results. Response-adapted therapy has yielded important results for patients with Hodgkin lymphoma and is becoming established as a standard approach.