American Society of Hematology (ASH) session co-moderator Matthew Genyeh Mei, MD, Associate Professor, Hematologic Malignancies and Stem Cell Transplantation Institute of City of Hope in Southern California, said the studies of checkpoint inhibitors in newly diagnosed and previously treated Hodgkin lymphoma, presented at the 2021 ASH Annual Meeting & Exposition, were encouraging and provided important new insights for practitioners.
Matthew Genyeh Mei, MD
‘Striking Clinical Synergy’
For background, Dr. Mei alluded to recent research showing a “striking clinical synergy” between PD-1 inhibition and cytotoxic chemotherapy in Hodgkin lymphoma. “For instance,” he said, “just in the past couple of years, we have seen the following: PD-1 blockade can resensitize patients to chemotherapy to which they have become resistant; autologous stem cell transplantation after checkpoint inhibition results in durable remissions. even in patients resistant to cytotoxic chemotherapy (so-called chemorefractory patients for whom transplant was thought to be ineffective); and the administration of pembrolizumab with doxorubicin, vinblastine, and dacarbazine in the first line and gemcitabine, vinorelbine, and liposomal doxorubicin in the second line are incredibly effective, with complete remission rates in excess of 90%. This far exceeds any results that have been obtained to date in either setting.”
The studies presented at the ASH meeting build upon those recent findings, further supporting PD-1 combinations, he told The ASCO Post. “Dr. Pam Allen, of Emory University, presented an update of sequential pembrolizumab followed by doxorubicin, vinblastine, and dacarbazine (AVD) from a trial whose preliminary data were published in 2021.1 In this updated analysis, with a median follow-up of 33 months, incredibly, still no patient has relapsed,” Dr. Mei noted. “Disease response was assessed after the three doses of pembrolizumab monotherapy; 19 of 30 patients had at least a 90% decline in metabolic tumor volume, and PD-L1 expression did not correspond to the depth of response to the pembrolizumab lead-in.”
Similar Concept
“Dr. Ryan Lynch, of the University of Washington, presented a similar concept with pembrolizumab and AVD, but this time, the regimen was given concurrently rather than sequentially. The 1-year progression-free survival rate was 96%, far exceeding historical controls. Correlative analysis of circulating tumor DNA (ctDNA) in a limited number of patients suggested that ctDNA may be more closely correlated with disease response than PET/CT [positron-emission tomography/computed tomography] scans,” he said.
“One interesting point was that the interim PET/CT scan after two cycles was positive in more than a third of patients; however, only one relapse was seen. This suggests that the interim PET/CT scan with PD-1 blockade may be of only limited prognostic significance in distinction to its high predictive value in patients treated with ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine],” he added.
Proof of Concept
“Finally, Dr. Locke Bryan, of Georgia Cancer Center, presented data on second-line therapy with pembrolizumab and ICE [ifosfamide, carboplatin, etoposide]. The complete metabolic remission rate was 86.5%, which was a little lower than what had been reported with pembrolizumab plus GVD [gemcitabine, vinorelbine, liposomal doxorubicin] earlier in 2021 but still significantly higher than historical control data with cytotoxic chemotherapy alone. Stem cell mobilization and engraftment were not affected,” Dr. Mei continued.
“To me, this is an important proof of concept, as pembrolizumab in conjunction with two separate chemotherapy backbones (ICE and GVD) has now been shown to have tremendous efficacy in the second-line setting, including in patients with primary refractory disease, for whom standard chemotherapy-based salvage therapy or even the novel salvage regimen of brentuximab vedotin and nivolumab have shown less-than-optimal results,” he said.
DISCLOSURE: Dr. Mei has received honoraria from Janssen and EUSA Pharma.
REFERENCE
1. Allen PB, Savis H, Evens AM, et al: Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood 137:1318-1326, 2021.
