The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Among patients with Waldenström macroglobulinemia (WM), CXCR4 mutation status does not appear to significantly impact progression-free survival (PFS) or duration after frontline treatment initiation (SAFTI) with a proteasome inhibitor-based therapy, researchers reported in a poster presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

“We conclude that there is no evidence that CXCR4 mutations adversely impact response, PFS, and SAFTI in WM patients receiving proteasome inhibitor-based primary therapy,” reported lead author Jorge J. Castillo, MD, and colleagues at the Bing Center for Waldenström’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, Massachusetts.

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WM harbors an activating somatic CXCR4 mutation in approximately 40% of patients, but the variants’ impact on treatment outcomes has been poorly studied.

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“Mounting evidence suggests that CXCR4 mutations adversely affect depth of response and progression-free survival (PFS) to ibrutinib in patients with WM,” the authors wrote on their poster.

To assess the effect of CXCR4 mutation on treatment responses, PFS and SAFTI, the authors analyzed pooled data from 76 patients who had undergone frontline proteasome inhibitor-based therapy.

“All patients were participants on 3 prospective clinical trials evaluating the combinations of bortezomib, dexamethasone, and rituximab (BDR; Identifer: NCT00250926), carfilzomib, dexamethasone, and rituximab (CaRD; Identifer: NCT01470196), and ixazomib, dexamethasone, and rituximab (IDR; Identifer: NCT02400437) in previously untreated patients with WM, and were treated at the Bing Center for WM,” the authors noted.

CXCR4 mutations were categorized as nonsense or frameshift mutations and treatment response was assessed. Thirty-six patients (55%) did not have CXCR4 mutations and CXCR4 mutation status was undetermined in 11 patients. Twenty-nine patients (45%) had a CXCR4 mutation; 16 had nonsense mutationsand 13 had frameshift CXCR4 mutations.

“There was a higher proportion of serum IgM levels ≥4000 mg/dl (62% vs 39%) and lower proportion of serum albumin levels ≤3.5 g/dl (21% vs 47%) in patients with than in patients without CXCR4 mutations,” the study authors reported in the abstract.

They concluded there were no detectable differences in major response rate at 6 months (P = 0.63) and 12 months (P = 0.71) between patients with and without CXCR4 mutations.

Disclosure: The authors disclosed financial relationships with AbbVie, BeiGene, Janssen, Pharmacyclics, TG Therapeutics, and Bristol-Myers Squibb.

Editor’s Note: The title of this article was updated to clarify that the researchers specifically studied the affect of CXCR4 mutations on progression-free survival in patients with WM being treated with proteasome inhibitors.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.


Castillo JJ, Gustine J, Demos M, et al. CXCR4 mutational status does not impact outcomes in patients with Waldenström macroglobulinemia treated with proteasome inhibitors. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 2830.