Blood Cancer
Michael Spinner, MD
University of California, San Francisco
Summary:
The current standard of care for relapsed or refractory classic Hodgkin lymphoma (cHL) is salvage chemotherapy followed by autologous stem cell transplant (ASCT), resulting in a cure for over 60% of patients. While ASCT is an effective treatment for chemosensitive patients, the highdose myeloablative chemotherapy that is used to kill cancer cells before the transplantation can cause significant and chronic toxicities and reduce quality of life. This includes life-threatening infections, kidney failure, and toxicity to the heart. Additionally, ASCT itself can cause infertility and up to 10% risk of a secondary cancer later in life. Furthermore, in addition to being physically taxing, ASCT is resource intensive for both the healthcare system and patients and can result in financial toxicity for patients as a single ASCT is estimated to cost over $140,000.
Recent studies have demonstrated that combing PD-1 inhibitors (an immune checkpoint inhibitor immunotherapy) with chemotherapy in relapsed/refractory cHL has resulted in complete remission rates of 80-90% without ASCT. One regimen in particular, pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) resulted in an unprecedented complete remission rate of 95%. The investigators hypothesize that many patients with relapsed/refractory cHL may be able to forgo ASCT with these improved regimens. They plan to utilize an ultrasensitive circulating tumor DNA-minimal residual disease (ctDNA-MRD) test in combination with PET imaging to identify patients with a low risk of relapse who can avoid ASCT. Patients that achieve a complete remission and are ctDNA-MRD negative after two cycles of pembro-GVD will receive will consolidation therapy with pembrolizumab and forgo ASCT. This phase II study will assess the ctDNA-MRD-negative and complete remission rate of pembro-GVD in patients with relapsed/refractory cHL. This trial will be the first to use real-time ctDNA sequencing to guide treatment decision making in patients with relapsed or refractory cHL.
Trial Registration: ClinicalTrials.gov Identifier: NCT07021989