Second-Line Pembrolizumab Plus GVD in Relapsed/Refractory Classical Hodgkin Lymphoma

Second-line pembrolizuab plus intravenous (IV) gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) led to high complete response (CR) rates in patients with relapsed/refractory classical Hodgkin lymphoma (cHL) and successfully bridged many of these patients to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). This is according to new findings published in the Journal of Clinical
Oncology.

The study, led by Alison Moskowitz, MD, of the Memorial Sloan Kettering Cancer Center, included 39 transplant-eligible patients with relapsed/refractory cHL. The most common frontline therapy received prior to enrollment was doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 36%).

Patients in this phase II trial received pembro-GVD therapy comprising:

  • IV pembrolizumab 200 mg on day 1
  • IV gemcitabine 1,000 mg/m2 on days 1 and 8
  • IV vinorelbine 20 mg/m2 on days 1 and 8
  • liposomal doxorubicin 15 mg/m2 on days 1 and 8

These agents were administered for two to four cycles, with each cycle lasting 21 days. Researchers examined the CR rate at up to four cycles of the second-line pembro-GVD regimen. Those whose disease achieved CR after two to four cycles subsequently received HDT/AHCT, while brentuximab vedotin was used as maintenance in some patients after the procedures.

In the overall cohort, the median age was 38 years. Approximately 41% of patients had primary refractory disease to first-line therapy. Another 38% of patients had relapsed disease within the first year of completing first-line therapy. Aside from ABVD, the second most common frontline therapy in the population was ABVD plus doxorubicin, vinblastine, and dacarbazine.

A total of 31 patients received two cycles of second-line pembro-GVD, while eight patients received four cycles. Adverse events (AEs) during the study treatment were most commonly grade 1 or 2. Grade 3 AEs during the study included transaminitis (n=4), neutropenia (n=4), mucositis (n=2), thyroiditis (n=1), and rash (n=1).

After four cycles of pembro-GVD, the overall CR rate was 95% (95% CI 82-99%), and the overall response rate after salvage therapy was 100% (95% CI 91-100%). The majority of patients (95%) were able to proceed to HDT/AHCT after 2 cycles (n=30) and 4 cycles (n=6) of pembro-GVD. One-third of patients received brentuximab vedotin maintenance or brentuximab vedotin plus nivolumab maintenance for a median of five cycles.

According to Dr. Moskowitz, the CR rate of 95% in this study is unprecedented, considering that other regimens in the second-line setting of cHL have historically ranged between 65% and 75%.

All patients were still alive and in remission after a median follow-up period of 13.5 months following HDT/AHCT. While five patients developed abnormalities on fluorodeoxyglucose-positron emission tomography following HDT/AHCT, cHL was not demonstrated on biopsies.

“Given that there is limited follow-up and the patients have done so well, we are unable to identify any markers or predictive factors that would help us determine who may end up relapsing down the road,” explained Dr. Moskowitz. She added that since the paper was published, one patient relapsed after 22 months following transplant. Longer-term follow-up may ultimately reveal additional relapses in this patient population, which means the current unprecedented results will become more balanced as time progresses.

Dr. Moskowitz noted that the study also raises further questions regarding the utility of AHCT in patients who achieve a second remission. “That is the standard of care based upon fairly old studies that were done in the era when we only had cytotoxic chemotherapy for treatment,” she said. “And now, with much more effective therapies, is it possible that a regimen such as pembro-GVD could induce remission for patients rather than require high-dose chemotherapy and AHCT?”

Study authors report relationships with Merck, the manufacturer of pembrolizumab.

Reference

Moskowitz AJ, Shah G, Schöder H, et al. Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma [published online ahead of print, 2021 Jun 25]. J Clin Oncol. doi: 10.1200/JCO.21.01056.