‘Outstanding Outcomes’ Support CHOP-Based Immunotherapy For High-Risk Follicular Lymphoma

Immunochemotherapy regimens are recommended to remain the standard induction therapy for patients with high-risk lymphoma

medwireNews: Long-term follow-up of the SWOG-S0016 trial shows “outstanding survival” among patients treated for high-risk follicular lymphoma with cyclophosphamide , doxorubicin , vincristine and prednisone alongside either rituximab (R-CHOP) or iodine131-tositumomab radioimmunotherapy (CHOP-RIT).

“At 10 years, almost 80% of the entire cohort was alive and 50% were disease free”, report Mazyar Shadman, from Fred Hutchinson Cancer Research Center in Seattle, Washington, USA, and co-investigators.

They comment in the Journal of Clinical Oncology: "This study provides the longest follow-up data on first-line treatment of [follicular lymphoma] using immunochemotherapy to our knowledge, and the clinical outcomes can serve as a benchmark in this setting."

For the study, 264 patients with stage III–IV disease or stage II bulky disease were randomly assigned to receive six 21-day cycles of CHOP plus rituximab 375 mg/m2 on days 1, 6, 48, 90, 134 and 141, while 267 were given CHOP followed by iodine131-tositumomab 4–8 weeks after cycle 6, calculated to give a 0.65–0.75 Gy whole-body dose.

The initial 2-year findings for R-CHOP and CHOP-RIT gave progression-free survival (PFS) rates of 76% versus 80%, while the overall survival (OS) rates were 97% versus 93%, the researchers say.

The current report, after a median of 10.3 years of follow-up, now gives an estimated10-year PFS rate of 42% for the R-CHOP arm versus 56% for the CHOP-RIT arm, a significant difference in favour of the latter regimen.

However, 10-year OS was a comparable 81% and 75% in the two groups, prompting the authors to “question the validity of PFS as a surrogate endpoint for OS in this patient population.”

Patients in the R-CHOP and CHOP-RIT arms also had statistically comparable rates of second malignancies (16.1 vs 15.1%) and myelodysplastic syndrome or acute myeloid leukaemia (MDS/AML; 1.8 vs 4.9%). The estimated 10-year rate of death from second malignancies did not significantly differ between the groups (3.2 vs 7.1%), although R-CHOP patients had a lower estimated incidence of death from MDS or AML than their CHOP-RIT counterparts (0.9 vs 4.0%).

The researchers emphasize, however, that as just 12 patients died from MDS or AML during follow-up, “these results should be interpreted with caution”.

Mazyar Shadman et al note that bendamustine-based regimens have become the “treatment of choice” for high-risk follicular lymphoma in recent years, with BRIGHT trial results showing non-inferiority to R-CHOP or rituximab plus cyclophosphamide, vincristine and prednisone. But they also point to the GALLIUM study results indicating a higher rate of fatal adverse events among patients who received bendamustine than CHOP in addition to either rituximab or obinutuzumab.

In addition, agents such as idelalisib, lenalidomide and venetoclax are under investigation as chemotherapy-free options for this population, they write.

“Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk [follicular lymphoma], with CHOP-based regimens as viable alternatives to bendamustine-based regimens”, the authors conclude.

“Our results offer a benchmark for comparison of future regimens.”

Reference

Shadman M, Li H, Rimsza L, et al. 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. J Clin Oncol; Advance online publication 22 January 2018. doi: 10.1200/JCO.2017.74.5083

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