Increasingly important prognostic role of IGHV mutational status1,2
>50% of the CLL population have unmutated IGHV 3*
- Mutated IGHV is independently associated with a relatively favorable prognosis4
- In contrast, patients with unmutated IGHV have poorer clinical outcomes4
The prognostic importance of IGHV mutational status
- IGHV mutational status was identified as an independent factor in the CLL-IPI for overall survival by multivariate analysis5
- iwCLL and NCCN Guidelines® both recommend testing for IGHV mutational status prior to treatment.4,7
- NCCN Guidelines stipulate that testing for IGHV mutation status is necessary when considering treatment with chemoimmunotherapy.7
Changes in iwCLL Guidelines4,6
|Baseline testing for IGHV mutational status|
|iwCLL 2018||iwCLL 2008|
|General practice||ALWAYS||Not generally indicated|
Bolding indicates updates.
*Defined as ≥98% homology to the nearest germ line gene sequence.
CLL=chronic lymphocytic leukemia, CLL-IPI=chronic lymphocytic leukemia-international prognostic index, IGHV=immunoglobulin heavy-chain variable region gene, iwCLL=International Workshop on Chronic Lymphocytic Leukemia.
Significance of del 17p and TP53 mutations
Recent guidelines in CLL also recommend testing for del 17p and for TP53 mutations, both shown to be predictive of poor outcomes.
References: 1. Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17(7) (suppl 2):928-942. 2. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848-1854. 3. Delgado J, Doubek M, Baumann T, et al. Chronic lymphocytic leukemia: a prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI. Am J Hematol. 2017;92(4):375-380. 4. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760. 5. International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17(6):779-790. 6. Hallek M, Cheson BD, Catovsky D, et al; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446-5456. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed April 15, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.