Bvgp: A Novel Protocol for Hodgkin's with Excellent Response, Minimal Acute Toxicities and Reduced Risk of Late Effects

Pediatric and Young Adult Hodgkin lymphoma (HL) has a five-year survival rate over 90%. The downside is use of chemotherapy with a lifetime risk of cardiac deaths, second malignancies, pulmonary disease and infertility. Because of effective salvage therapy, ultimate outcomes may be improved by using effective but less toxic initial therapy. To this end, we have piloted a regimen in low and intermediate risk HL using agents not known to be associated with significant late effects. The BVG regimen {bortezomib 1.3 mg/m² IV day 1,4,8,11; vinorelbine (25 mg/m² IV day 1,8); gemcitabine (1000 mg/m² IV day 1,8) every 21 days} was derived from BIGEV [Ding 2009] with elimination of ifosfamide, etoposide and prednisone. Initial use was to consolidate 3 patients after ABVE-PC. Subsequently we treated 5 newly diagnosed patients with non-bulk stage IIA (n=4) or IIB (n=1) HD. Two received BVG and 3 received BVGP with the addition of prednisone (20 mg/m²/dose PO BID x 11 days). Nausea was mild and controlled with 5HT3 antagonists and scopolamine patch. Pegfilgrastim was not necessary due the high absolute neutrophil count nadir (median 1.16 & minimum 0.56 x 10⁹/L). There were no episodes of febrile neutropenia, infections or need for transfusions. There were no significant abnormalities in electrolytes, renal or liver function tests. No patients had any hair loss. One patient developed sensory neuropathy, after dose 8 of bortezomib, that responded to gabapentin and a switch to subcutaneous administration. Newly diagnosed patients were all PET negative after 1 or 2 cycles and remained PET negative at the end of four cycles of therapy. Status of the five newly diagnosed patients ages 10 to 18 is: one is still on therapy; three in remission at 158, 312, 1015 days; one relapsed at 861 days in previous disease sites. This retrospective chart review was approved by Children's Minnesota IRB. For each patient an in depth discussion was held on the benefits and risks of BVGP vs. standard therapy. The chief barrier to use of the protocol was insurance coverage for bortezomib in patients under the age of 18. We hope this abstract will provide early evidence to allow expansion of this pilot experience leading to a randomized trial comparing BVGP with current chemotherapy for low and intermediate Young Adult and Pediatric HL.