In a large proportion of patients with relapsed or refractory Hodgkin lymphoma (HL), nivolumab monotherapy was an effective bridge therapy to autologous hematopoietic cell transplantation (AHCT), according to interim results from a phase II trial presented at the 2019 ASH Annual Meeting. This approach could help to reduce toxicity often observed with standard salvage chemotherapy in this setting, the investigators, led by Alex Herrera, MD, from City of Hope in Duarte, California, noted.
The findings were shared by co-author Matthew Mei, MD, also from City of Hope. “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 lead to a number of efforts to lessen toxicity of salvage treatments and incorporate newer agents.”
In this prospective, multicenter trial, researchers evaluated a positron emission tomography (PET)-adapted treatment strategy. Patients with relapsed or refractory HL received salvage therapy with nivolumab 3 mg/kg every two weeks for up to six cycles. Participants underwent PET-computed tomography (PET-CT) at cycle 3 and cycle 6. If patients were in complete remission (CR) at cycle 6, they proceeded to AHCT; if patients had not achieved CR, they received nivolumab plus ICE chemotherapy (ifosfamide, carboplatin, and etoposide; NICE) for two cycles.
A total of 39 participants were evaluable for toxicity at the time of presentation, while 37 were evaluable for the primary endpoint of CR. At the time of data presentation, 32 patients had completed study therapy, two were continuing on study protocol. The remaining five participants discontinued early due to proceeding to AHCT (n=1), nivolumab-related adverse events (AEs; n=2), death unrelated to study treatment (n=1), and refusal to receive NICE following nivolumab (n=1).
Overall, including participants who discontinued early, the overall response rate (ORR; defined as partial response or better) was 78%, with CR and PR rates of 70% and 8%, respectively. At the end of nivolumab cycle 3, the ORR was 89%, including a CR rate of 59% (n=22) and a PR rate of 30% (n=11). After cycle 6, the ORR rate in the remaining 31 patients was 90%, with CR and PR rates of 77% (n=24) and 13% (n=4), respectively.
All seven patients who had either stable or progressive disease per PET-CT during and after salvage nivolumab monotherapy responded to treatment with NICE, including six CRs (86%) and one PR (14%).
By the end of study protocol, the ORR was high across both groups of patients at the end of study protocol, at 89%. Again, most of these were CRs (n=32; 86%).
Twenty-seven participants who completed six cycles of single-agent nivolumab proceeded to AHCT directly after salvage therapy, while four refused transplant.
Over a median follow-up period of 12 months (range = 0.5-28.6), the 1-year progression-free and overall survival rates were 74% and 97%. There were two events of progressive disease after AHCT that occurred in patients who required treatment with NICE.
Dr. Mei reported that “the toxicity [associated with this treatment protocol] is fairly minor overall, [so] the patients are going to transplant in better shape, as well.” Of those who received nivolumab monotherapy, the most common grade 1-2 AEs included fatigue (28%), rash (18%), fever (15%), and thrombocytopenia (10%). Two patients experienced grade 3-4 nivolumab-related AEs. However, in those who received nivolumab plus chemotherapy, the most frequently reported grade 1-2 AEs were nausea (71%), vomiting (57%), anemia (43%), fatigue (43%), hypertension (43%), and hyponatremia (29%).
Although this was a single-arm study, Dr. Mei noted that he and fellow researchers were surprised by the unexpectedly high CR rate with nivolumab, independent of ICE chemotherapy. When asked by an audience member about the potential costs of using nivolumab alone as bridging therapy, he said, “you do save the hospitalization costs of only two or three 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.”
Limitations of the study include the lack of a placebo control group, the small patient sample, and the relatively short follow-up duration.
Dr. Herrera reported a relationship with Bristol-Myers Squibb, the manufacturer of nivolumab.
Herrera AF, Chen RW, Palmer J, et al. PET-adapted nivolumab or nivolumab plus ICE as first salvage therapy in relapsed or refractory Hodgkin lymphoma. Abstract #239. Presented at the 2019 ASH Annual Meeting, December 7, 2019; Orlando, FL.