A chemoimmunotherapy regimen led to a 100% response rate as second-line therapy for relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), a small phase II trial showed.

All 38 evaluable patients achieved objective responses with the combination of pembrolizumab (Keytruda), gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD), including complete responses in 36 of 38 cases. All but two of the patients subsequently underwent high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) and remained in remission after a median post-transplant follow-up exceeding a year.

The results suggest P-GVD has potential as an effective and efficient bridge to AHCT, but also raise the question of whether every patients with RR cHL requires aggressive therapy, stated Alison Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues, in the Journal of Clinical Oncology.

“The standard of care is for patients to get a stem-cell transplant, so I think the question now is there any chance that there’s a group of patients who can avoid that,” Moskowitz told MedPage Today.

“We didn’t find any difference in response based on a patient’s stage or burden of disease,” she added. “The complete response rate was quite high, regardless of whether patients had primary refractory disease or relapsed disease, so I really think it’s a reasonable approach to consider for anyone who has relapsed/refractory disease. I think the standard of care at this point would be to use a treatment like this as a bridge to an autotransplant, and studies looking at a nontransplant approach is really investigational at this point.”

As many as 25% patients with advanced-stage and 10% with early-stage cHL will have RR disease. The current standard of care is second-line therapy followed by consolidation with HDT/AHCT, the authors noted.

Recent studies in RR disease have shown 2-year progression-free survival (PFS) of 70% or better. Key factors in improved outcomes have been pre-HDT/AHCT response by FDG-PET imaging and introduction of newer therapies, such as brentuximab vedotin (Adcetris, BV), they continued.

No single standard-of-care second-line therapy exists for RR cHL, and several different chemotherapy regimens have been shown to induce complete responses in 50%-60% of patients. Regimens that incorporate newer therapies, including BV and PD-1 inhibitors, have produced complete response rates of 67%-75%.

Data remain limited for results with incorporation of PD-1 blockade into second-line therapy, the authors continued. The combination of nivolumab (Opdivo) and BV can be administered in the outpatient setting with good tolerability and leads to complete responses in two-thirds of patients and a 3-year PFS of 77%.

Continuing the investigation of chemoimmunotherapy for R/R cHL, Moskowitz and colleagues evaluated P-GVD as second-line therapy prior to HDT/AHCT. Investigators in the phase II, two-center trial enrolled 39 adult patients with R/R cHL, which was primary refractory disease in 41% of cases and relapse within 1 year of frontline therapy in 38%.

Treatment consisted of two cycles of P-GVD in 31 patients and four cycles in the remaining eight. Response assessment by FDG-PET occurred after two cycles of therapy. Patients who achieved less than complete response received two more cycles of P-GVD, followed by FDG-PET assessment and consideration for HDT/AHCT. BV maintenance was allowed following HDT/AHCT.

No dose-limiting toxicity occurred, and most adverse events (AEs) were grade 1/2 in severity. The most frequently reported AEs were rash (49%), elevated liver enzymes (41%), oral mucositis (38%), nausea (36%), fatigue (31%), headache (23%), and infusion-related reaction (21%). Grade 3 AEs consisted of four cases each of elevated liver enzymes and decreased neutrophil count, two cases of oral mucositis, and one each of rash and hypothyroidism.

Immune-related AEs included hyperthyroidism in five patients, transaminitis in 16, and rash in 19.

After two cycles of P-GVD, 35 of 38 (92%) patients achieved complete remission, and the remaining three patients had partial responses. Of seven patients who received an additional two cycles of therapy, five achieved complete remission and two had partial responses.

Subsequently, 36 of the 38 evaluable patients proceeded to HDT/AHCT. Thirteen patients received posttransplant BV and one received BV and nivolumab. Of the two patients who did not undergo AHCT, one withdrew for personal reasons after achieving a complete response to two cycles of P-GVD, and the other declined transplant in favor of off-study pembrolizumab maintenance. The patient who received pembrolizumab maintenance remained in remission 16 months after completing maintenance therapy.

Follow-up continues in the original cohort, and enrollment has begun in a second cohort of patients who will be treated with P-GVD, said Moskowitz. Additionally, correlative studies will be conducted in a search for more insight to the therapy’s mechanism of action and for potential biomarkers.