Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus ¹³¹I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016

Abstract

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.

Genomic alterations important for the prognosis in patients with follicular lymphoma treated in SWOG study S0016

“…In addition, SWOG S0016 did not apply the standard of care in both arms. Based on the equivalent outcome between the CHOP-R and CHOP-RIT arms, we may infer that the prognostic significance of these markers would extend to FL patients treated with CHOP-R. 1 Prospective studies on patients under the current standard of care, including a bendamustin-based regimen, will further strengthen the discovery of our study.…”

“…The recent 10-year update on followup outcome demonstrated better progression-free survival (PFS), but not OS, in the radioimmunotherapy arm. 1 We previously showed that lactate dehydrogenase, b2M, and FLIPI scores were significantly correlated with outcome, 13 but histological grades were not. 14 In this study, we aimed to identify clinically useful genomic aberrations by chromosomal genomic-array testing (CGAT) to help predict patients who will progress within 2 years and who will have worse PFS and OS.…”

Risk of secondary haematological malignancies in patients with follicular lymphoma: an analysis of 1028 patients treated in the rituximab era

“…After a 10‐year follow‐up, five patients (1·8%) treated with R‐CHOP and 13 patients (4·9%) treated with CHOP‐RIT had developed MDS or AML. Of these patients, 12 died due to secondary MDS or AML (Shadman et al , ). In another study of NHL patients treated with CHOP, the RR for leukaemia was 14·2 (95% CI: 6·8–26·2) and it was 19·2 (95% CI: 9·6–34·3) in patients treated with chlorambucil (Mudie et al , ).…”

Long‐term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non‐Hodgkin lymphoma

“…Among 563 patients with indolent NHL enrolled in Gruppo Italiano Studio Linfomi trials, Sacchi et al () reported 12 cases of MDS/AML at a median follow‐up of 62 months, with age at first treatment being a significant risk factor for second cancer. Among 526 patients treated on the Southwest Oncology Group S0016 trial with a median follow‐up of 9·6 years from start of therapy, 3% of patients had developed MDS/AML, increased from 1% after 4·9 years of follow‐up (Press et al , ; Shadman et al , ). By comparison, the annual population risk of developing MDS or AML in individuals aged over 65 years is roughly 30 per 100 000 and 20 per 100 000 in the United States [Surveillance, Epidemiology, and End Results (SEER) Program, ].…”