Nivolumab (Opdivo) monotherapy can be used as an effective bridge therapy to autologous stem-cell transplant (ASCT) in many patients with relapsed or refractory Hodgkin lymphoma, reported Matthew Mei, MD, Assistant Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, at ASH 2019.
Nivolumab plus chemotherapy has been used as salvage therapy before transplant in this patient population. The interim results from a prospective, multicenter, single-arm phase 2 clinical trial of 37 patients who were evaluable for response showed an overall response rate (ORR) of 92%, with a complete response rate of 78% at the end of nivolumab treatment alone before transplant, said Dr Mei.
“In the relapsed setting for Hodgkin lymphoma, the standard of care remains salvage chemotherapy followed by ASCT in chemotherapy-sensitive patients,” Dr Mei said. “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 the toxicity of salvage treatments and incorporate newer agents.”
Nivolumab Alone or with Chemotherapy
Dr Mei and colleagues evaluated a treatment strategy guided by positron emission tomography (PET). Patients with relapsed or refractory Hodgkin lymphoma received salvage therapy with nivolumab 3 mg/kg every 2 weeks, for up to 6 cycles. Patients underwent PET-computed tomography at cycle 3 and cycle 6. If patients achieved a complete response at cycle 6, they proceeded to ASCT.
If patients had not achieved a complete response, they received nivolumab plus a chemotherapy regimen with ifosfamide, carboplatin, and etoposide (ICE) for 2 cycles.
Patients were eligible if they had relapsed or refractory CD30-positive Hodgkin lymphoma and received a maximum of 1 previous line of systemic therapy. Patients who previously received consolidation radiation were allowed in the study.
A total of 43 patients were enrolled in the study. Some 86% of patients received the front-line regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine. Of the 43 patients, 34 (79%) received nivolumab only and 9 (21%) received nivolumab plus ICE. A total of 36 (84%) patients completed treatment, and treatment is ongoing in 2 patients.
A total of 5 participants discontinued the study before the end of treatment, including 1 patient who proceeded to ASCT early, 2 who had nivolumab-related toxicity, 1 death (sepsis) that was unrelated to nivolumab, and 1 patient who refused treatment with nivolumab plus ICE after receiving nivolumab monotherapy. A total of 30 (70%) patients underwent ASCT directly after protocol therapy.
High Response Rate
At the end of nivolumab treatment cycle 3, the ORR was 90%, including a complete response rate of 58%. After nivolumab cycle 6, the ORR in the remaining 37 patients was 92%, with a complete response rate of 78%. The ORR in 41 patients at the end of protocol therapy was 90%, and the complete response rate was 88%.
Over a median follow-up of 12 months, the progression-free survival rate at 1 year was 74%, which included 3 patients who achieved complete response after nivolumab alone, subsequently refused a transplant, and had disease progression.
The complete response 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 the patients who received nivolumab monotherapy, the most common grade 1 or 2 adverse events included fatigue (28%), rash (18%), fever (15%), and thrombocytopenia (10%). Two patients had grade 3 or 4 nivolumab-related adverse events. In the patients who received nivolumab plus chemotherapy, the most frequently reported grade 1 or 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,” noted Dr Mei.