Ibritumomab Tiuxetan Ups Survival in Tough-to-Treat Diffuse Large B-Cell Lymphoma

Many patients with aggressive B-cell non-Hodgkin lymphoma (NHL) are cured of the disease after short-course chemotherapy and radiation. Certain adverse risk factors, though, make relapse more likely. Ibritumomab tiuxetan as add-on to standard chemoradiotherapy offers new hope for these patients, according to results from a Southwestern Oncology Group (SWOG) trial recently published in Blood.

In SWOG S0313, investigators found that pairing the radio-labeled anti-CD20 antibody with standard CHOP and involved field radiation therapy (IFRT) in high-risk patients with diffuse large B-cell lymphoma (DLBCL) led to high estimated progression-free survival (PFS): 89 percent at two years, 82 percent at five years, and 75 percent at seven years. High-risk was defined as >60 years of age, non-bulky stage II disease, elevated LDH, and World Health Organization performance status ≥2.

Overall survival (OS) estimates were similarly promising the authors, led by Daniel O. Persky, MD, of the University of Arizona in Tucson, reported.

“Using radioimmunotherapy consolidation is at least as effective as using rituximab upfront with chemotherapy for the treatment of early-stage diffuse large B-cell lymphoma,” Dr. Persky told ASH Clinical News.

While ibritumomab was the first radioimmunotherapy approved by the Food and Drug Administration in 2002 for use in relapsed or refractory low-grade B-cell NHL, the investigators decided to test ibritumomab in the current setting because “this form of radioimmunotherapy has the potential to prevent systemic spread and distant relapse of disease.”

They enrolled 46 patients with a diagnosis of aggressive NHL, including diffuse large B-cell, mantle cell, Burkitt, or Burkitt-like histologies, and all patients had at least one stage-modified adverse risk factor.

During the 2004 to 2008 study period, 42 of the 46 patients completed all planned therapies: CHOP was administered at standard doses on days 1, 22, and 43, followed three weeks later by 40-50 Gy of IFRT. A maximum of six weeks after IFRT, patients received rituximab with Yttrium-90 ibritumomab consolidation. If scans showed acceptable biodistribution of ibrutimomab tiuxetan, rituximab was repeated later.

After a median follow-up of 7.3 years, Dr. Persky and colleagues estimated OS and PFS rates of:

  • 91 and 89 percent at two years
  • 87 and 82 percent at five years
  • 82 and 75 percent at seven years

The PFS and OS rates of the current study (S0313) compared favorably with previous SWOG studies of similar patients, specifically S8736 (CHOP3 + IFRT) and S0014 (3 cycles of rituximab + CHOP + IFRT). Five-year OS and PFS rates were 79 and 72 percent in S8736, and 83 and 82 percent in S0014.

There were also no unexpected toxicities with ibritumomab treatment.

Finally, the authors found that ibritumomab tiuxetan regimen in the current study was associated with fewer relapses than in the previous SWOG studies: 7 percent of patients in S0313 relapsed or died between years 2 and 5, versus 13 and 15 percent in S8736 and S0014, respectively.

So, can this regimen be adopted now? According to Dr. Persky, hematologists should wait for results from the ongoing Intergroup trial (S1001), which pairs rituximab with CHOP and ibritumomab consolidation after IFRT. Those results could offer even more support for radioimmunotherapy in early-stage DLBCL with adverse risk factors.

“The standard of care is still using rituximab with chemotherapy upfront in early-stage DLBCL,” he said. “The ongoing S1001 trial will help us to decide if low-risk patients may omit radiation – there is evidence from other studies to support that possibility – and if high-risk patients will benefit from addition of radioimmunotherapy consolidation. So, I think this is still work in progress,” he told ASH Clinical News.


References

Persky DO, Miller TP, Unger JM, et al. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015;125:236-24.

SHARE