A retrospective study suggests a four-drug regimen can be effective salvage therapy for patients with relapsed or refractory classical Hodgkin lymphoma.
The regimen – brentuximab vedotin plus ifosfamide, gemcitabine, and vinorelbine (BV-IGEV) – produced responses in 27 of 28 patients studied, allowing them to undergo autologous hematopoietic stem cell transplant (HSCT).
After HSCT, the estimated 2-year progression-free survival (PFS) was 87.1% and the overall survival (OS) was 73.5%.
Though this study was limited by its small population and retrospective nature, the results “warrant further investigation,” according to Khadega A. Abuelgasim, MD, of King Abdullah International Medical Research Center in Riyadh, Saudi Arabia, and colleagues.
The researchers reported the results in a letter to Bone Marrow Transplantation.
The study included 28 patients with classical Hodgkin lymphoma, 15 of them male. The patients’ median age at HSCT was 25 years (range, 15-49 years). Twenty patients (71%) had constitutional symptoms at diagnosis, and eight (29%) had bulky disease.
Twenty-three patients (82%) received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy, and four (14%) received ABVD followed by escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. One patient received a different frontline regimen.
The median time to relapse was 7.9 months (range, 1.9-133 months), and 12 patients (43%) were refractory to frontline treatment.
Half of patients (n = 14) received BV-IGEV as first salvage. The regimen was given as follows: ifosfamide at 2,000 mg/m2 on days 1-4, gemcitabine at 800 mg/m2 on days 1 and 4, vinorelbine at 20 mg/m2 on day 1, prednisolone at 100 mg on days 1-4, and BV at a dose of 1.8 mg/kg on day 1 of each 3-week IGEV course.
All patients received at least two cycles of BV-IGEV and were assessed for response after one or two cycles. The median follow-up was 17 months (range, 0-65 months).
Twenty patients (71%) had a complete metabolic response to BV-IGEV, seven (25%) had a partial metabolic response, and one patient (4%) had stable disease. The patient with stable disease went on to receive another salvage regimen and achieved a partial response to that regimen.
The most common adverse events during BV-IGEV treatment were grade 3-4 neutropenia (n = 27; 96%) and thrombocytopenia (n = 25; 89%). Febrile neutropenia was also common (n = 16; 57%), as were mucositis (n = 6; 21%) and diarrhea (n = 6; 21%). Six patients had a reduction in BV dose because of an adverse event.
All patients underwent autologous HSCT. They received carmustine, etoposide, cytarabine, and melphalan as conditioning beforehand, and 18 patients (64%) received consolidative BV after transplant.
PFS and OS were calculated from the date of stem cell infusion. The estimated 2-year PFS was 87.1%, and the estimated 2-year OS was 73.5%.
Patients who received BV-IGEV as first salvage fared better than those who received the regimen as second salvage. The PFS rates were 100% and 75%, respectively (P = .0078), and OS rates were 100% and 50%, respectively (P = .08).
Six patients relapsed after HSCT, and three died. Two patients died of progressive disease and one died of pulmonary infection.
These results suggest BV-IGEV can produce high response rates without compromising stem cell mobilization, but the combination should be investigated further, according to the researchers.
The researchers reported having no conflicts of interest.
SOURCE: Abuelgasim KA et al. Bone Marrow Transplant. 2019 Jan 30. doi: 10.1038/s41409-019-0454-z.