Non-Chemo Regimen Highly Active in R/R Hodgkin Lymphoma

Three-fourths of patients with relapsed/refractory Hodgkin lymphoma remained alive without disease progression 3 years after treatment with nivolumab (Opdivo) and brentuximab vedotin (Adcetris), a prospective multicenter trial showed.

Patients who proceeded to autologous stem-cell transplant (ASCT) after nivolumab-brentuximab treatment had a 3-year progression-free survival (PFS) of 91%. The 3-year overall survival (OS) was 93%.

Adverse events were generally mild or moderate and self-limiting. Immune-related adverse events requiring systemic corticosteroids occurred in 18% of the patients, reported Ranjana H. Advani, MD, of Stanford University in California, and colleagues, in Blood.

“BV (brentuximab vedotin) and nivolumab as initial salvage therapy, together with ASCT, was well tolerated and provided durable remissions in a high proportion of patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL),” the authors concluded. “These data continue to support the promise of combining BV and nivolumab as a salvage regimen that is highly active and well tolerated and may potentially offer an alternative to chemotherapy-based salvage in patients with r/r cHL.”

The authors of an accompanying editorial agreed that “this regimen has the potential to provide an alternative to cytotoxic chemotherapy regimens such as ifosfamide, carboplatin, and etoposide as a first salvage therapy, if the findings are confirmed in a randomized trial.”

“Optimal sequencing of the brentuximab-nivolumab regimen with standard salvage chemotherapy and other immunotherapies and the evolving role for stem-cell transplant (SCT) as a function of highly active second-line salvage regimens remain important questions for future studies,” stated Yun Choi, MD, and Catherine Diefenbach, MD, both of Perlmutter Cancer Center at NYU Langone Health in New York City.

“Future studies in relapsed HL should focus on addressing the questions of what the most effective transplant salvage regimens are and whether there are therapies that can obviate the need for SCT in select subsets of patients,” they added. “Advani et al provide a compelling rationale to study the brentuximab-nivolumab regimen further in a randomized fashion with other regimens to answer the former question, but the latter question will be more challenging to address.”

From 10%-30% of patients with cHL are refractory to initial treatment or relapse after initial response. Salvage chemotherapy, followed by ASCT, remains the standard of care, and patients who achieve complete metabolic response after salvage chemotherapy have significantly better long-term relapse-free survival after ASCT. As a result, identifying regimens that are both well tolerated and offer high complete-response rates have been the focus of ongoing research, the authors noted in their introduction.

The antibody-drug conjugate brentuximab vedotin demonstrated single-agent activity in r/r cHL. BV also showed promise as salvage therapy when administered sequentially or in combination with chemotherapy, the authors continued. Nivolumab also showed promise as treatment for r/r cHL, leading to an objective response rate of 73% and complete responses in 28%. BV and nivolumab are generally well tolerated, providing a rationale to evaluate the combination in r/r cHL.

Investigators conducted a multicenter, single-arm phase I/II trial involving adults with biopsy proven r/r cHL. The protocol excluded patients who had received prior salvage therapy. Both staggered dosing and same-day dosing of BV and nivolumab were evaluated during the trial. At the end of BV-nivolumab treatment, patients could proceed to ASCT at investigator discretion. Immune-related adverse events occurred in 16 patients, none of whom discontinued treatment.

Data analysis included 91 patients who received treatment. The combination of BV and nivolumab led to an objective response rate of 85%, including a complete response rate of 67%. Subsequently, 67 patients underwent ASCT. After a median follow-up of 34.3 months, the estimated PFS was 77% in all patients and 91% in those who proceeded to ASCT.

The most common treatment-emergent adverse events prior to ASCT were nausea (52% of patients), infusion-related reactions (43%), and fatigue (40%), all but one of which were grade I/II (one episode of grade 3 fatigue). Overall, 30 grade ≥3 adverse events occurred, including five cases of neutropenia. Two patients discontinued because of adverse events (one case each of peripheral neuropathy and gamma-glutamyltransferase).