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Brentuximab vedotin with chemotherapy, radiation effective for unfavorable risk Hodgkin lymphoma
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Treatment with brentuximab vedotin and chemotherapy, followed by involved-site radiation therapy, induced a high rate of complete response in patients with early-stage, unfavorable risk classical Hodgkin lymphoma, according to the results of a multicenter pilot study.
Chemotherapy plus radiation therapy is the standard of care for patients with early-stage, unfavorable risk classical Hodgkin lymphoma. Although studies have shown that a chemotherapy-alone approach can improve outcomes in some patients, many of these studies excluded patients with bulky disease. Due to a concern for toxicity from radiation when used in a combined-modality approach, many patients now receive reduced doses with involved-nodal radiation.
Brentuximab vedotin (Adcetris, Seattle Genetics) appears highly active in the treatment of patients with relapsed and refractory Hodgkin lymphoma. However, limited data exist on the agent’s safety and efficacy when used with combined-modality treatment for front-line therapy.
Anita Kumar, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues evaluated the use of brentuximab vedotin in combination with chemotherapy and involved-site radiation therapy in 30 newly diagnosed patients (median age, 31 years; range, 18-59) with unfavorable risk disease. All patients had stage II disease.
Patients received four cycles of brentuximab vedotin with adriamycin, vinblastine and dacarbazine chemotherapy. All but one patient — who left the study after one cycle due to toxicity — received the four cycles.
PET scans were performed after the second and fourth treatment cycles. Patients who achieved a PET–negative response after four cycles, or who had a negative biopsy despite PET positivity, received 30 Gy of involved-site radiation therapy. Twenty-six patients (90%) had a negative scan after the second cycle, and 27 (93%) had a negative scan after the fourth.
Patients with a positive PET scan and biopsy continued treatment off study. Four patients did not receive involved-site radiation therapy, including two patients with biopsy-confirmed refractory disease. One patient came off study and elected to receive proton beam radiotherapy to the mantle field; the remaining patients received additional chemotherapy alone.
All 25 patients who received four cycles of brentuximab vedotin and chemotherapy, followed by involved-site radiation therapy, achieved a complete response. No cases of relapse occurred during a median follow-up of 18.8 months.
The median PFS in the entire intent-to-treat population was 93.3% (95% CI, 84-102).
Fifty-three percent of patients (n = 16) developed grade 3 or worse neutropenia. Six patients experienced serious adverse events, including febrile neutropenia (n = 3), fever without neutropenia (n = 2), and grade 3 hypertension with peripheral motor and sensory neuropathy (n = 1).
Grade 1 or grade 2 adverse events related to radiation therapy included fatigue (n = 22), dermatitis (n = 20), dysphagia (n = 20) and esophagitis (n = 13). No clinically significant drug-related pneumonitis occurred.
The researchers acknowledged that their sample size was not large enough to perform a robust efficacy assessment, but reported that they have expanded their initial cohort by adding an additional 29 patients.
“The early results from this study demonstrate promising efficacy with high rates of PET negativity and complete response,” Kumar and colleagues wrote. “Recent data from British Columbia Cancer Agency reports excellent outcomes for [patients with Hodgkin lymphoma] with disease bulk who achieve a negative PET scan after full-course [adriamycin, bleomycin, vinblastine and dacarbazine] without additional consolidative radiation therapy. Future studies to test whether radiotherapy can be eliminated or its volume further reduced in PET–negative bulky early-stage Hodgkin lymphoma patients treated with brentuximab vedotin and chemotherapy are warranted.” – by Cameron Kelsall
Disclosure: Kumar reports research funding from Seattle Genetics. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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