NCCN Guidelines Include Obinutuzumab in CLL

Anita T. Shaffer
Published Online: May 12, 2014
This illustration depicts the obinutuzumab antibody binding to the CD20
antigen on the B-cell surface.

This illustration depicts the obinutuzumab antibody binding to the CD20 antigen on the B-cell surface. [Image courtesy of Genentech]

Amid advances in targeted therapies for patients with chronic lymphocytic leukemia (CLL), researchers also have been making strides in the realm of chemoimmunotherapy regimens for the disease. In November, the FDA approved obinutuzumab (Gazyva) in combination with chlorambucil for patients with previously untreated CLL. The first-in-class glycoengineered type-2 antibody has demonstrated superior outcomes in combination with chlorambucil to both a rituximab (Rituxan) plus chlorambucil regimen and to chlorambucil alone.1,2 The obinutuzumab combination has been incorporated into the National Comprehensive Cancer Network (NCCN) guidelines (Table).3 The NCCN guidelines panel will discuss the most current research when it meets in June to consider any further updates, according to William G. Wierda, MD, PhD, who serves on the panel.

Wierda discussed therapies for CLL at the 18th Annual International Congress on Hematologic Malignancies, which was held mid-February, 2014 in New York City. Clinical trial findings published in The New England Journal of Medicine4 in January support the efficacy of obinutuzumab for olderage patients and those with comorbidities or renal insufficiencies, said Wierda, who is a professor at The University of Texas MD Anderson Cancer Center in Houston, in an interview during the conference.

“If I have a patient who needs front-line therapy who is elderly and who is not appropriate for standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, my first choice would be obinutuzumab plus chlorambucil,” Wierda said. “The data clearly support that as a superior treatment over other treatment options for the elderly patient population or patients with comorbidities.”

The phase III German CLL Study Group trial enrolled 781 patients with a median age of 73 years, a median creatinine clearance of 62 mL per minute, and a median baseline score of 8 on the Cumulative Illness Rating Scale, according to Goede et al. In the 3-arm trial, patients were randomized to receive chlorambucil plus either obinutuzumab or rituximab, or chlorambucil alone.

Both combination regimens delivered better outcomes than chlorambucil alone. Moreover, the obinutuzumab combination significantly prolonged progression-free survival (hazard ratio [HR] = 0.39; 95% CI: 0.31-0.49; P <.001) and demonstrated higher rates of complete response (20.7% vs 7.0%) compared with the rituximab regimen.

In terms of adverse events (AEs), researchers reported higher rates of AEs of grade 3 or higher severity among patients who received chlorambucil, with neutropenia and infusion-related reactions among the two most frequently reported AEs.

NCCN Guidelines for Obinutuzumab in CLL1

Frail patient with significant comorbidity (not able to tolerate purine analogues)
  • Obinutuzumab + chlorambucil as 1st preference
First-line therapy for patients without del 11q or 17p
  • Obinutuzumab + chlorambucil as 1st preference for patients aged ≥70 y, or younger with comorbidities
  • Obinutuzumab + chlorambucil among chemoimmunotherapy options for patients aged <70 y, or older without significant comorbidities
First-line therapy for patients with del 17p
  • Obinutuzumab + chlorambucil among combination therapy options
First-line therapy for patients with del 11q
  • Obinutuzumab + chlorambucil as 1st preference for patients aged ≥70 y, or younger with comorbidities
  • Obinutuzumab + chlorambucil among chemoimmunotherapy options for patients aged <70 y, or older without significant comorbidities

CLL indicates chronic lymphocytic leukemia; del, chromosomal deletion; NCCN, National Comprehensive Cancer Network.
1. NCCN Guidelines Non-Hodgkin’s Lymphomas Version 1.2014. Updated December 20, 2103. Accessed March 8, 2014.



Related Articles
The bromodomain inhibitor, OTX015, may have use in the treatment of hematologic malignancies, including acute leukemia and other hematologic malignancies that include lymphomas and multiple myeloma.
The FDA has expanded the approval of ibrutinib (Imbruvica) to include the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one previous therapy and harbor a 17p deletion.
John C. Byrd, MD, a professor of Medicine at The Ohio State University Comprehensive Cancer Center, discusses updates in the treatment of CLL.
JTT Articles
Targeting Radiotherapy in the Liver: SIR-Spheres®
HPV Test With Genotyping Supplants Pap Test
Androgen-Targeting Therapies Increasing in CRPC
External Resources

AJMC
HCPLive
OncLive
PainLive
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Internal Resources

Articles
Fellows
Publications
Targeted Communications
Resources
Connect With Us:

About Us
Advertise
Contact Us
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright TargetedOnc 2013
Intellisphere, LLC. All Rights Reserved.