The results of a phase 2 study looking at treating relapsed or refractory Hodgkin lymphoma with a new drug protocol were outstanding. They even surprised one of the world’s leading lymphoma experts, Craig Moskowitz, M.D., physician in chief of the Oncology Service Line at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.
Dr. Moskowitz, who co-wrote the protocol, is senior author of the study, published June 25 in the Journal of Clinical Oncology.
Dr. Moskowitz collaborated with colleagues at Memorial Sloan Kettering Cancer Center to study the treatment, which included checkpoint inhibitor pembrolizumab along with chemotherapies gemcitabine, vinorelbine and liposomal doxorubicin. Investigators treated 36 transplant-eligible Hodgkin lymphoma patients who had not responded to frontline medications or relapsed within a year of treatment.
“All the patients treated with our protocol are in remission. These are the best results reported in the literature in the setting of relapsed or refractory Hodgkin lymphoma,” Dr. Moskowitz said. “We actually believe because of these results that a paradigm shift is possible in the next series of refractory Hodgkin lymphoma clinical trials.”
Offering new options
While frontline therapies cure Hodgkin lymphoma patients in most cases, up to 25% of those with advanced stage disease and 10% with early-stage Hodgkin lymphoma do not respond to frontline medications or their disease returns. These relapsed and refractory patients traditionally are treated with a second line of chemotherapy, which bridges them to stem cell transplant. About 75% of responding patients to second line chemotherapy go on to stem cell transplant, of whom 60% are cured.
Investigators in this study evaluated 38 patients with relapsed or refractory Hodgkin lymphoma who had received either two or four cycles of the protocol. While there were adverse events, the treatment was generally well tolerated, according to the study.
All patients in the study achieved remission with the protocol. Thirty-six patients proceeded to stem cell transplants, and all of those patients remain in remission an average 13.5 months post-transplant.
Another important advantage of the protocol is that it is administered in the outpatient setting.
“Historically all the patients in the relapsed refractory patient setting were admitted to the hospital for treatment,” said Dr. Moskowitz, who is also professor of medicine at the Miller School.
Pembrolizumab alone has been shown to have significant palliative activity in Hodgkin lymphoma patients who are doing poorly, according to Dr. Moskowitz, who has studied pembrolizumab since 2012.
“In 2018, we decided to use pembrolizumab outside of the palliative setting and then combine it with a standard program that was outpatient with the hope that this program would be efficacious, well tolerated and enable the majority of patients to go to a cure with stem cell transplant,” he said.
Promising phase 2 results
The results of the new phase 2 trial are so promising that Dr. Moskowitz and colleagues believe that using the protocol could eliminate the need for stem cell transplant in many cases.
“Because so many of the patients achieved remission, we believe it is possible that transplant may be able to be avoided,” he said. “Rather, we could administer these four simple medications in our protocol, with maintenance pembrolizumab for another six months.”
Sylvester is collaborating with Memorial Sloan Kettering to treat an additional 25 patients without a stem cell transplant.
“If patients do well without a stem cell transplant, this will likely lead to a national study comparing this program versus an alternative program with a stem cell transplant, to see if we can truly remove autologous stem cell transplant from the management of first relapsed Hodgkin lymphoma and save it for a rainy day,” Dr. Moskowitz said.
Sylvester hematologist and medical oncologist Georgios Pongas, M.D., also is an author on the study.