Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma: Final Results of a Phase II Study

Abstract

Background: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. Methods: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4–6 weeks later if there was no disease progression and bone marrow biopsy showed < 25% involvement. Results: Twenty-eight patients were treated, with a median age of 61 years, median of 3 prior therapies, 49% high-risk disease (Follicular Lymphoma International Prognostic Index, FLIPI), and 39% progressive disease. Three patients did not receive Zevalin due to residual bone marrow involvement. The main toxicities were cytopenias, with 11% febrile neutropenia. The overall response rate (ORR) was 72%, with 45% achieving complete response. With a median follow-up of 73 months, 1-year progression-free survival (PFS) was 38%, and median PFS was 10 months, but median overall survival (OS) was not reached. Conclusion: The study did not reach its primary endpoint of a 1-year PFS of 67.3%. Reasons for this could include low accrual, high-risk disease, and inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was associated with tolerable toxicity, high ORR, and high OS. Further studies would optimize debulking and focus on high-risk FL patients.

Radioimmunotherapy (RIT) for Follicular Lymphoma achieves long term lymphoma control in first line and at relapse: 8‐year follow‐up data of 281 patients from the international RIT‐registry

“…However, most of the patients (87%) had received chemo‐ and not chemoimmunotherapy prior to consolidation in this trial (Marcus et al , ), and therefore this trial could not determine whether RIT improves the outcome of patients treated with the current standard of anti‐CD20 antibody and chemotherapy, followed by anti‐CD20 antibody maintenance. Nevertheless, several smaller phase II trials have shown an increased CR rate after 90 Y‐IT consolidation (Provencio et al , ; Pisani et al , ; Casadei et al , ; Puvvada et al , ) following induction with CHOP and rituximab (R‐CHOP) as compared to R‐CHOP induction alone. However, a 2‐year maintenance with rituximab or obinutuzumab (Salles et al , ; Marcus et al , ), instead of 90 Y‐IT consolidation, is currently common practice after first line chemotherapy.…”

Real World Long-term Follow-up Experience with Yttrium-90 ibritumomab tiuxetan in Previously Untreated Patients with Low-Grade Follicular Lymphoma and Marginal Zone Lymphoma

“…This also aligns with the incidence of t-MDS/AML in (90)Y-IT studies in relapsed/refractory NHLs which was up to 10% and with (90)Y-IT use as a consolidation therapy following induction chemoimmunotherapy which was 3%. [19][20][21][22][23][24] It appears that the interaction of prior or recent exposure to CIT and (90)Y-IT plays an important role in pathogenesis of t-MDS/AML.…”

A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma

“…Puvvada also hypothesized that RIT eliminated minimal residual disease after cytoreduction in FL, thus facilitating durable complete remissions. 16 Twenty-eight patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) every 28 days, followed by 90Y-IT 4 to 6 weeks later if there had been no disease progression and <25% bone marrow involvement. The ORR was 72%, with 45% achieving CR.…”