The Chemotherapy Regimen IVAC Is Highly Active for Multiply Relapsed and Refractory Hodgkin Lymphoma

Hodgkin Lymphoma (HL) has a cure rate of 70% with chemotherapy or combined modality therapy. Despite this success, approximately 5–10% of patients have primary refractory disease, and 20–30% of patients will relapse after initial complete remission (CR). Second-line chemotherapy and autologous stem cell transplant (ASCT) approaches are curative for only 50% of patients with relapsed/refractory disease. Maximal cytoreduction prior to ASCT confers the greatest potential benefit, yet the current standard salvage chemotherapy regimens have a low CR rate despite a high overall response rate (ORR), and survival is poor for patients who relapse after ASCT. Allogeneic stem cell transplantation can induce durable remissions in some patients with relapsed and primary refractory HL; however the use of this modality is limited in part by the challenges of achieving adequate disease control prior to transplantation. Novel treatment platforms to maximally debulk these patients and allow them to proceed to successful transplantation are needed. Our group has treated multiply relapsed HL patients with the chemotherapy regimen of Ifosfamide, Etoposide, and Cytarabine (IVAC) and we report a retrospective chart review detailing our experience.

Between January of 2011 and June of 2012, 4 patients with relapsed or primary refractory HL were treated with the chemotherapy regimen IVAC consisting of: Ifosfamide 1,500mg/m2 days 1–5; MESNA 1,500mg/m2 days 1–5, Etoposide 600mg/m2 days 1–5, and Cytarabine 2,000mg/m2 q 12hrs × 4 doses days 1–2 given every 21 days. All patients received growth factor support beginning 24hrs after completion of chemotherapy. All patients received prophylactic antifungal, antiviral, and PCP prophylaxis. Restaging PET/CT was performed after 2 cycles of therapy. All patients received 2 cycles of therapy prior to assessment for transplant.

Four patients have been treated to date on this regimen. The mean age of the 4 patients was 35.5 (range 32–43). All patients were male. All patients were heavily pre-treated with a mean of 8 prior chemotherapy regimens (range 7–9) including ICE (Ifosfamide, Carboplatin, Etoposide) and Brentuximab vedotin. Three of the 4 patients had prior stem cell transplant: autologous (n=2), allogneic with subsequent DLI (n=1). All patients tolerated the chemotherapy well. The most common significant adverse events were: grade 3 pneumonia (1/4 patient), grade 3 febrile neutropenia (1/4 patients), grade 3 neutropenia (4/4 patients), grade 3 anemia (4/4 patients), grade 3 thrombocytopenia (4/4 patients). All patients recovered to baseline before initiating cycle 2, and after the completion of therapy. Response was evaluated after 2 cycles of therapy in all patients. Three of 4 patients (75%) had a response giving an ORR rate of 75%. Two of the 3 responding patients had a CR giving a CR rate of 50%, 1 patient had a PR. Response duration was: 6 weeks (n=1), 3 months (n=1), 6 months (n=1).

IVAC is highly active, even in heavily pre-treated HL patients, with an ORR of 75% and a CR rate of 50%. With close clinical monitoring hematologic and infectious toxicities were manageable in all patients. The regimen of IVAC may allow disease debulking for multiply relapsed HL patients prior to stem cell transplant. Prospective evaluation of this therapy is ongoing.

No relevant conflicts of interest to declare.