Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group

Abstract

Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL.

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.…”

“…Efficacy of 90 Y‐ ibritumomab‐tiuxetan ( 90 Y‐IT, Zevalin ® ), the only currently commercially available RIT, has been demonstrated in distinct clinical trials, e.g. as consolidation after first line chemo(immuno)therapy (Witzig et al , ; Morschhauser et al , ; Provencio et al , ; Casadei et al , ), at relapse (Witzig et al , ) and even as a monotherapy for first line treatment (Scholz et al , ; Ibatici et al , ). 90 Y‐IT can be administered in an outpatient setting and its side effects, particularly cytopenia between week 6 and 9 after application, are manageable.…”

Long‐term complication in follicular lymphoma: assessing the risk of secondary neoplasm in 242 patients treated or not with 90‐yttrium‐ibritumomab‐tiuxetan

“…With respect to their use as single agent or as consolidation after previous therapy, the landscape is not so clear, but it is accepted that the combination of RIT with intense chemotherapy regimens like HYPERCVAD (hyperfractionated cytarabine, vincristine, adryamicin, dexamethasone) could lead to bad outcomes with higher risk of toxicities, risk of mortality, and SPNs' development, including a high incidence of MDS (28); however, some data favor the association of RIT with R-CHOP regimen (29). In the SWOG S0016 phase III randomized to R-CHOP or CHOP + RIT consolidation trial (11), it was found that after 4.9 yr of median follow-up, from the 263 patients included in each arm, the incidence of SPNs was equal, 23 patients for R-CHOP arm (9%) vs. 22 (8%) patients in the CHOP-RIT arm; in this study, 131 Iodine-Tositumomab agent was used; quite similar results were reported by Morschausser et al (15) after 7.3-yr follow-up of the FIT trial; and in that study, 414 patients were randomized to consolidated with 90Y-IT or watch & wait (W&W), after achieved at least PR after first-line therapy; they found that the rate of SPNs was not different in both arms (26 for 90Y-IT vs. 14 for W&W, P = 0.86), but they found a higher risk to developed MDS/AML among patients receiving 90Y-IT.…”

Long term efficacy and safety of Fludarabine, Cyclophosphamide and Rituximab regimen followed by 90Y-ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma

“…In the current retrospective analysis, nine patients with relapsed grade 1 and 2 FL, responding to FCR regimen and consolidated with 90 Y–RIT obtained a significant high rate of response with 100 % of CR and acceptable toxicity. The conversion from PR to CR was already shown in the published phase III study (FIT-study) in first-line FL [ 3 , 4 ] and also in phase II studies [ 5 – 12 ] of consolidation with the radioimmunotherapy agent 131 I-tositumomab after first-line induction [ 19 , 20 ] thus, confirming the ability of 90 Y-RIT to improve responses also in patients who are pretreated with rituximab based combination therapy [ 3 ]; even if in our two patients there is no proof that this conversion was due to RIT and not to a late response to FCR. In the FIT study, close to 17 % of the patients in the control arm, converted from PR to CR during watchful waiting [ 3 ], but our 2 patients who had higher risk of resistance already being pretreated must be considered.…”