Orlando, FL—Nivolumab monotherapy can be used as an effective bridge therapy to autologous hematopoietic cell transplantation (AHCT) in many patients with relapsed or refractory Hodgkin lymphoma (HL), researchers reported at the 2019 American Society of Hematology (ASH) annual meeting.
Interim results from a prospective, multicenter, single-arm phase 2 trial of 37 patients evaluable for response showed an overall response rate (ORR) of 92%, with a complete response (CR) rate of 78% at the end of nivolumab alone, said the study’s co-investigator Matthew Mei, MD, Assistant Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.
“In the relapsed setting for HL, the standard of care remains salvage chemotherapy followed by AHCT in chemotherapy-sensitive patients,” said Dr Mei. “And, while chemotherapy-based salvage therapies work fairly well and [are associated with] a high response rate, they also lead to substantial toxicity, which leads to a number of efforts to lessen toxicity of salvage treatments and incorporate newer agents.”
Dr Mei and colleagues evaluated a treatment strategy guided by positron emission tomography (PET). Patients with relapsed or refractory HL received salvage therapy with nivolumab 3 mg/kg every 2 weeks, for up to 6 cycles. Patients underwent PET-computed tomography (PET-CT) at cycle 3 and cycle 6. If patients achieved a CR at cycle 6, they proceeded to AHCT; if patients had not achieved a CR, they received nivolumab plus ICE (ifosfamide, carboplatin, and etoposide) chemotherapy for 2 cycles.
Eligible patients were those with relapsed or refractory CD30-positive HL who received a maximum of 1 previous line of systemic therapy.
A total of 43 patients were enrolled in the trial. Approximately 86% of patients received the front-line regimen of A(B)VD (doxorubicin, bleomycin, vinblastine, and dacarbazine). Of the 43 patients, 34 (79%) received nivolumab only and 9 (21%) received nivolumab plus ICE. Thirty-six (84%) patients completed treatment, and treatment is ongoing in 2 patients.
Five participants discontinued the study before end of treatment, including 1 who proceeded to AHCT early, 2 who had nivolumab-related toxicity, 1 death (sepsis) unrelated to nivolumab, and 1 who refused treatment with nivolumab/ICE after nivolumab monotherapy. Thirty (70%) patients underwent AHCT directly after protocol therapy.
At the end of nivolumab cycle 3, the ORR was 90%, including a CR rate of 58%. After nivolumab cycle 6, the ORR in the remaining 37 patients was 92%, with a CR rate of 78%. The ORR in 41 patients at the end of protocol therapy was 90% and the CR rate was 88%.
Over a median follow-up of 12 months, progression-free survival at 1 year was 74%, which included 3 patients who achieved CR after nivolumab alone, subsequently refused AHCT, and had disease progression.
The CR rate with nivolumab was unexpectedly high, independent of ICE chemotherapy, said Dr Mei. Nivolumab alone as bridging therapy does “save the hospitalization costs of only 2 or 3 cycles of ICE. So, I don’t think this is a more expensive route, and if we can save hospitalization costs by avoiding ICE, I think that’s a good thing,” he said.
Of those who received nivolumab monotherapy, the most common grade 1/2 adverse events included fatigue (28%), rash (18%), fever (15%), and thrombocytopenia (10%). Two patients had grade 3/4 nivolumab-related adverse events. In those who received nivolumab plus chemotherapy, the most common grade 1/2 adverse events were nausea (71%), vomiting (57%), anemia (43%), fatigue (43%), hypertension (43%), and hyponatremia (29%).
“The toxicity [associated with this treatment protocol] is fairly minor overall, [so] the patients are going to transplant in better shape, as well,” said Dr Mei.