Pediatric Hodgkin Lymphoma
Ilia Buhtoiarov1, Nkechi Mba2, Crystal De Los Santos2, Kathleen M. McCarten3, Monika L. Metzger4, Qinglin Pei5, Rizvan Bush6, Kara M. Kelly7, Aron Flagg1, Rabi Hanna1, Peter Cole8
1 Cleveland Clinic Children's Hospital, Cleveland, OH, 2 Driscoll Children's Hospital, Corpus Christi, TX, 3 Imaging and Radiation Oncology Core Rhode Island, Lincoln, RI, 4 St. Jude Children's Research Hospital, Memphis, TN, 5 University of Florida, Gainesville, FL, 6 Children's Oncology Group, Monrovia, CA, 7 Roswell Park Cancer Institute, Buffalo, NY, 8 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
Background: High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) improves long-term outcomes for patients with primary treatment-refractory classical Hodgkin lymphoma (cHL) or those with early relapse. Most novel salvage regimens are currently developed as a “”bridge”” to transplant, with the objective of producing a metabolic complete response prior to preceding to HDC/ASCR. However, an increasing body of clinical experience suggests that some patients with relapsed cHL can be cured without undergoing HDC/ASCR. The Children's Oncology Group protocol AHOD1221 (NCT01780662) tested the efficacy of a novel combination, Brentuximab Vedotin with Gemcitabine (Bv+G). By central review, 28 of 42 patients with primary refractory cHL or early relapse experienced a complete response. The majority, 34 of 42 underwent stem cell transplantation.
Results: Two patients who experienced biopsy proven early relapses of cHL after standard therapy were enrolled in AHOD1221 and treated with Bv+G. Their clinical characteristics and treatment course is summarized in the Table. Both subjects achieved a second CR within four cycles of Bv+G, but declined to proceed to HDC/ASCR. Both remained on study treatment for more than 10 months. One patient stopped therapy after 14 cycles, due to persistent grade 2 peripheral neuropathy. Her neurologic symptoms resolved over the subsequent 8 months. The second patient was taken off study therapy, per protocol, after completion of 16 cycles (1 year of treatment) with no adverse events reported in the final cycles. Neither subject has experienced a subsequent relapse, more than a year since their last cycle of Bv+G.
Conclusions: Although this series describes only two subjects with one year follow-up, both patients have experienced a second relapse-free survival that has exceeded the duration of first CR. The results suggest that some patients with early relapse of cHL may be cured with prolonged treatment using Bv+G, without high-dose chemotherapy and stem cell rescue. Additional clinical study of transplant-avoiding salvage strategies may be warranted.